DRS

As confidentially submitted with the Securities and Exchange Commission on March 26, 2021

Registration No. 333-                

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Cyteir Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	2834	45-5429901
(State or other jurisdiction of incorporation or organization)	(Primary Standard Industrial Classification Code Number)	(I.R.S. Employer Identification No.)

128 Spring St, Building A, Suite 510

Lexington, MA 02421

857-285-4140

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Markus Renschler, M.D.

President and Chief Executive Officer

128 Spring St, Building A, Suite 510

Lexington, MA 02421

857-285-4140

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Marc Rubenstein, Esq. Tara Fisher
Ropes & Gray LLP
Prudential Tower 800 Boylston Street
Boston, MA 02199-3600
(617) 951-7000 Deanna L. Kirkpatrick, Esq. Yasin Keshvargar, Esq. Davis Polk & Wardwell LLP 450 Lexington Avenue New York, NY 10017 (212) 450-4000

Approximate date of commencement of proposed sale to the public:

As soon as practicable after the effective date of this Registration Statement.

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box.  ☐

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
		Emerging growth company	☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act.  ☐

CALCULATION OF REGISTRATION FEE

Title of each class of securities to be registered	Proposed maximum aggregate offering price(1)(2)	Amount of registration Fee(3)
Common Stock, par value $0.001 per share	$	$

(1) Estimated solely for the purpose of calculating the registration fee pursuant to Rule 457(o) under the Securities Act of 1933, as amended.

(2) Includes the aggregate offering price of additional shares that the underwriters may purchase pursuant to an option to purchase additional shares.

(3) To be paid in connection with the initial filing of the registration statement.

The registrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this Registration Statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

The information in this prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

Subject to completion, dated                 , 2021

Preliminary prospectus

             shares

Common stock

This is an initial public offering of shares of common stock of Cyteir Therapeutics, Inc. We are selling                  shares of our common stock. The initial public offering price is expected to be between $                 and $                 per share.

We have applied for listing of our common stock on the                  under the symbol “CYT.”

We are an “emerging growth company” under federal securities laws and are subject to reduced public company reporting requirements. See “Prospectus Summary—Implications of Being an Emerging Growth Company.”

	Per share	Total
Initial public offering price	$	$
Underwriting discounts and commissions(1)	$	$
Proceeds to Cyteir Therapeutics, Inc., before expenses	$	$

(1) We have agreed to reimburse the underwriters for certain FINRA-related expenses. See “Underwriting” for additional disclosure regarding underwriting compensation.

We have granted the underwriters an option for a period of 30 days to purchase up to                  additional shares of common stock from us at the initial public offering price, less underwriting discounts and commissions.

Investing in our common stock involves a high degree of risk. See “Risk Factors” beginning on page 11 of this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities, or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.

The underwriters expect to deliver the shares to purchasers on or about                , 2021.

J.P. Morgan Morgan Stanley BofA Securities

Wedbush PacGrow

                     , 2021.

Table of contents

	Page
Prospectus summary		1
The offering		8
Summary consolidated financial data		10
Risk factors		11
Special note regarding forward-looking statements		60
Use of proceeds		61
Dividend policy		62
Capitalization		63
Dilution		65
Selected financial data		68
Management’s discussion and analysis of financial condition and results of operations		69
Business		83
Management		130
Executive and director compensation		139
Certain relationships and related party transactions		148
Principal stockholders		151
Description of capital stock		154
Shares eligible for future sale		159
Material U.S. federal income tax consequences to non-U.S. holders of our common stock		162
Underwriting		166
Legal matters		175
Experts		175
Where you can find additional information		175
Index to consolidated financial statements		F-1

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Neither we nor the underwriters have authorized anyone to provide any information other than that contained in this prospectus or in any free writing prospectus prepared by or on behalf of us or to which we have referred you. We take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you. We and the underwriters are not making an offer to sell these securities in any jurisdiction where the offer or sale is not permitted. You should assume that the information appearing in this prospectus is accurate only as of the date on the front cover of this prospectus, regardless of the time of delivery of this prospectus or any sale of our common stock. Our business, financial condition, results of operations and prospects may have changed since that date.

For investors outside of the United States: Neither we nor the underwriters have done anything that would permit this offering or possession or distribution of this prospectus in any jurisdiction where action for that purpose is required, other than the United States. Persons outside of the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of the shares of common stock and the distribution of this prospectus outside of the United States.

Through and including                , 2021 (the 25th day after the date of this prospectus), all dealers effecting transactions in these securities, whether or not participating in this offering, may be required to deliver a prospectus. This delivery requirement is in addition to the obligation of dealers to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions.

Trademarks

We use CYTEIR and CYTEIR THERAPEUTICS as trademarks in the United States and/or in other countries. This prospectus contains references to our trademarks, trade names and service marks and to those belonging to other entities. Solely for convenience, trademarks, trade names and service marks referred to in this prospectus, including logos, artwork and other visual displays, may appear without the ^® or TM symbols, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks, trade names and service marks. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity.

Market and industry data

Unless otherwise indicated, information contained in this prospectus concerning our industry and the markets in which we operate, including our general expectations, market position and market opportunity, is based on our management’s estimates and research, as well as industry and general publications and research, surveys and studies conducted by third parties. We believe that the information from these third-party publications, research, surveys and studies included in this prospectus is reliable. Management’s estimates are derived from publicly available information, their knowledge of our industry and their assumptions based on such information and knowledge, which we believe to be reasonable. This data involves a number of assumptions and limitations which are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including those described in “Risk Factors.” These and other factors could cause our future performance to differ materially from our assumptions and estimates.

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Prospectus summary

This summary highlights information included elsewhere in this prospectus. This summary does not contain all the information you should consider before investing in our common stock. You should read and consider this entire prospectus carefully, including the sections titled “Risk Factors,” “Special Note Regarding Forward-Looking Statements” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the related notes included elsewhere in this prospectus, before making any investment decision. Unless the context otherwise requires, the terms “Cyteir,” “Cyteir Therapeutics,” the “Company,” “we,” “us” and “our” relate to Cyteir Therapeutics, Inc.

Overview

We are a clinical-stage biotechnology company focused on developing and commercializing the next-generation of precision oncology medicines that inhibit deoxyribonucleic acid, or DNA, damage repair and cause cancer cell death through a therapeutic strategy known as synthetic lethality. Synthetic lethality represents a clinically validated approach to drug development and arises when there is a deficiency in either of two conditions that are tolerable alone in cells but lethal together. Our lead program, CYT-0851, as well as our next generation drug candidate CYT-1853, exploits a novel gain-of-function synthetically lethal relationship between overexpression of a family of DNA damaging genes called cytidine deaminases, or CDs, and functional inhibition of homologous recombination, or HR, a DNA repair pathway critical for the survival of some cancers. CYT-0851 is a novel, potentially first-in-class, oral small molecule inhibitor of RAD51-mediated HR. We are investigating CYT-0851 in a phase 1/2 trial in adult patients with hematologic malignancies and solid tumors, and have observed encouraging preliminary single agent activity in the dose escalation portion of the trial. If warranted by the phase 1/2 data, and subject to U.S. Food and Drug Administration, or FDA, agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors. We also plan to develop CYT-0851 in additional tumor settings as both a monotherapy and in combination with approved cancer therapeutics and plan to initiate dosing in a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021.

Cells have complex, coordinated DNA damage repair pathways to ensure genome integrity. Several DNA repair pathways have been identified as essential for repairing the myriad forms of DNA damage our cells experience, such as non-homologous end joining, or NHEJ, and HR. NHEJ repairs double stranded DNA, or dsDNA, breaks by directly rejoining the two broken ends, an error-prone pathway that can introduce DNA mutations. HR is critical for the error-free repair of dsDNA breaks by using the sister DNA strand as a template to restore the broken DNA strand to its original sequence. HR is thereby able to preserve the normal function of damaged genes by preventing the introduction of DNA mutations. Activity of this highly coordinated network of DNA damage sensing and repairing pathways is collectively called the DNA Damage Response, or DDR.

A hallmark feature of cancer cells is the accumulation of DNA mutations, many of which drive the aggressive characteristics of cancer cells, such as uncontrolled cell proliferation, invasion of surrounding tissues and, importantly, resistance to standard therapies. DNA damage, while a driver of normal cells becoming cancer cells, can trigger cell death when it accumulates to lethal levels. To survive, cancer cells become dependent on error-free DNA repair pathways, preventing them from reaching lethal levels of DNA damage. Consequently, they often become more vulnerable than normal cells to therapeutic inhibition of those same DNA repair pathways, which are made up of hundreds of individual proteins and potential drug targets. The figure below depicts how cells utilize DDR pathways to repair damaged DNA, and how the increased levels of DNA damage that cancer cells incur can make them more dependent on DNA damage repair and more sensitive to DDR-targeted therapy.

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Cancer cells become dependent on DNA damage repair pathways

The physiological role of Activation-Induced Cytidine Deaminase, or AID, a member of the CD family, expressed primarily in activated B cells of the immune system, is to augment our immune response to pathogens by enabling diverse antibody production. However, when AID is overexpressed, as it often is in certain forms of cancer, such as B-cell lymphomas, it leads to genome-wide DNA damage and collateral mutations (see the figure below). To avoid cell death, cancer cells frequently activate DNA damage repair pathways, including HR, to properly repair the harmful damage to genes that are vital for the cancer’s survival. This increased dependency on HR presents a therapeutic opportunity in those cancers overexpressing AID. Like AID, the Apolipoprotein B mRNA Editing Catalytic Enzymes, or APOBEC, genes which are also members of the CD family, have been shown to induce cancer causing DNA damage when constitutively overexpressed and functionally dysregulated. The APOBEC3 genes are normally involved in viral immunity and are induced downstream of interferon signaling in response to viral infections. They are also often highly expressed in cancers and are thought to play a major role in driving cancer progression in subsets of solid tumors, such as head and neck, breast, and lung cancers.

AID induces physiological (beneficial) and pathological (harmful) DNA damage

Capitalizing on this therapeutic opportunity, we developed a platform to discover small molecule HR inhibitors, without regard to molecular target, based on the observation that AID-overexpressing B cells are dependent on HR for their survival. CYT-0851 is the result of extensive medicinal chemistry efforts optimizing early hits from this novel drug screening platform.

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Our approach to drug discovery and development

We are using our expertise in DDR biology and a disciplined approach to select targets for other novel, differentiated drug discovery and development programs. Our approach includes:

• systematically prioritizing DDR targets based on our deep understanding of DDR biology, coupled with the mining of mutational information collected on diseased tissues and the analysis of results from both internal and external CRISPR-based genetic, chemical and cellular phenotypic synthetic lethality screens;

• elucidating synthetic lethality dependencies of our drug targets and using that information to molecularly define patient populations most likely to benefit from our therapies as a monotherapy, and maximizing tumor selectivity that limits side effects and allows our drugs to be used in combination with other standard anti-cancer therapies;

• developing potent, highly selective, well tolerated, small molecule therapies against these targets and evaluating them in biomarker-selected in vitro and in vivo model systems; and

• expeditiously progressing lead candidates through preclinical studies and into focused clinical trials in defined patient populations using a biomarker-guided approach.

Our core capabilities in discovery biology focusing on DNA damage repair has enabled us to move rapidly and efficiently from drug discovery to clinical development. We have the management team with the successful global registration experience to potentially advance our drug candidates to registration. In only three years, we progressed CYT-0851 from discovery to clinical proof of concept. In 2021, we intend to define the optimal development plan for potentially achieving accelerated approval of CYT-0851 initially as monotherapy in late lines of treatment for certain lymphomas and/or solid tumors. In addition, we may broaden the target patient population in both hematologic malignancies and solid tumors and move to earlier lines of treatment, either alone and/or in combination with standard-of-care therapies.

Our pipeline

The following chart summarizes our clinical product pipeline. We hold worldwide development and commercialization rights to our drug candidates.

Our programs

Our lead program, CYT-0851, is a novel, oral, once-daily, potential first-in-class, small molecule inhibitor of RAD51-mediated HR with a potentially high therapeutic index. In the dose escalation portion of our ongoing phase 1/2 trial of CYT-0851, we have enrolled 37 patients as of March 16, 2021, and have an aggregated analysis

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on 23 of these patients from December 8, 2020. At this analysis, ten patients were considered response-evaluable, and we observed preliminary evidence of clinical benefit with four patients achieving stable disease, and two patients with diffuse large B-cell lymphoma, or DLBCL, and soft tissue sarcoma achieving a partial response. Of these 23 patients, 26% reported relatively mild (primarily grade 1 and 2) treatment-related adverse events and 74% did not report any treatment-related adverse events. This tolerable safety profile reported to date distinguishes CYT-0851 from most other approved cancer drugs and those in development that employ similar synthetically lethal strategies to treat cancer. We plan to advance CYT-0851 into monotherapy phase 2 expansion in seven tumor-specific patient groups beginning in the second half of 2021. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors.

To expand the potential of CYT-0851 beyond monotherapy use, we have conducted preclinical studies to explore combinations with a variety of standard-of-care anti-cancer drugs and have observed synergistic treatment effects. We believe the encouraging preclinical results in conjunction with the favorable monotherapy clinical activity and tolerability of CYT-0851 to date provide a strong rationale for the development of a combination therapy in the future. Many of these therapies work by exacerbating DNA damage in cancer cells, which puts stress on DDR pathways and potentially creates a synergistic opportunity with CYT-0851 treatment. We anticipate dosing the first patient in combination with other approved anti-cancer therapies in the second half of 2021.

To complement CYT-0851, we are developing CYT-1853 as a next generation inhibitor of RAD51-mediated HR. Importantly, in preclinical models, CYT-1853 is also synthetically lethal in CD-overexpressing cancer cells, is active across a range of cancer cell lines, and exhibits improved potency compared to CYT-0851. We are planning to complete investigational new drug, or IND, enabling studies in 2021 and to file an IND in 2022.

Furthermore, we have identified an undisclosed second target, a protein in one of the DNA repair pathways other than HR, as well as subsets of cancers that depend on this protein for their survival. We have identified a potential biomarker for use in candidate development and, ultimately, patient selection. Importantly, expression of this protein is prognostic, meaning patients whose cancer cells overexpress this protein generally have shorter survival compared to patients whose cancer cells do not. We are in the discovery stage of this program, and we anticipate reaching the drug candidate nomination stage and initiating IND-enabling studies in 2022.

Our management team

We have assembled a management team of biopharmaceutical industry veterans with extensive experience in developing novel oncology therapies, including advancing drug candidates from preclinical research through clinical development and ultimately regulatory approval and commercialization. We have extensive experience across the spectrum of drug research and development, with direct involvement in developing and commercializing drugs such as Imbruvica^® (ibrutinib), REVLIMID^® (lenalidomide), POMALYST^® (pomalidomide), ABRAXANE^® (nab-paclitaxel), VIDAZA^® (azacytidine) and others. Our team is led by our President and Chief Executive Officer, Markus Renschler, M.D., who has over 25 years’ experience at Celgene Corporation, Pharmion Corporation and Pharmacyclics in building successful biopharmaceutical companies. Paul Secrist, Ph.D., our Chief Scientific Officer, has over 25 years’ experience in drug discovery and pre-clinical development at OSI Pharmaceuticals, Aton Pharma, Merck Inc., and AstraZeneca. Andrew Gengos, our Chief Business Officer, has over 25 years’ experience in strategic, operational, and financial roles at both emerging and established companies in the biopharmaceutical sector, including McKinsey & Company, Chiron, ImmunoCellular Therapeutics, and Amgen Inc. Thomas O’Shea, Ph.D., our Senior Vice President of Clinical Pharmacology and

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Preclinical Development has over 25 years’ experience at Sanofi, Genzyme, AstraZeneca, Pharmacia, and Searle & Co. Inc.

We have raised more than $140 million of capital since inception from a group of leading life sciences investors, including Novo Holdings, Droia Ventures, Venrock, Osage University Partners, Lightstone Ventures, RA Capital Management and Janus Henderson Investors, as well as Celgene Corporation, or Celgene, a global biotechnology company that merged with Bristol-Myers Squibb Company.

Strategy

Our goal is to be the leading biopharmaceutical company developing and commercializing next generation precision oncology medicines that inhibit DDR and cause cancer cell death through synthetic lethality. We employ an integrated drug discovery approach with a streamlined drug development process that leverages our team’s distinguished success bringing medicines to the market with the aim to build a patient-centric portfolio of effective cancer therapies.

The key elements of our strategy are to:

• build upon the differentiated profile and encouraging preliminary single-agent activity of our lead drug candidate, CYT-0851, to rapidly advance it through clinical development and regulatory approval;

• leverage CYT-0851’s favorable monotherapy clinical activity and tolerability to develop it in combination with DNA damaging drugs, such as chemotherapy or poly-ADP ribose polymerase, or PARP, inhibitors;

• advance our next generation inhibitor of RAD51-mediated HR, CYT-1853, through clinical development and regulatory approval to complement CYT-0851;

• utilize our deep understanding of DDR and tumor biology to identify novel drug candidates and expand our pipeline; and

• maximize the value of our drug candidates and pipeline while selectively evaluating strategic collaborations.

Risks associated with our business

Our business is subject to a number of risks of which you should be aware before making an investment decision. These risks are discussed more fully in the “Risk Factors” section of this prospectus immediately following this prospectus summary. These risks include the following:

• We have a limited operating history and have no products approved for commercial sale, which may make it difficult for you to evaluate our current business and predict our future success and viability.

• We have incurred significant losses since inception. We expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

• Even if we consummate this offering, we will need substantial additional funding. If we are unable to raise capital when needed, we will be forced to delay, reduce, or eliminate our research and product development programs or future commercialization efforts.

• We have never successfully completed any clinical trials, and we may be unable to do so for any drug candidates we develop.

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• Our clinical trials may fail to demonstrate adequately the safety and efficacy of any of our drug candidates, which would delay or prevent further clinical development of those candidates, or prevent marketing approval from FDA or similar regulatory authorities.

• We intend to develop CYT-0851, and potentially future drug candidates, for use in combination with other therapies, which exposes us to additional risks.

• If we are unable to successfully develop and commercialize companion diagnostic tests for our drug candidates, or experience significant delays in doing so, we may not realize the full commercial potential of our drug candidates.

• Synthetic lethality represents an emerging class of precision medicine targets, and negative perceptions of the efficacy, safety or tolerability of this class of targets, including any that we develop, could adversely affect our ability to conduct our business, advance our drug candidates or obtain regulatory approvals.

• If we are unable to adequately protect and enforce our intellectual property or obtain and maintain patent protection for our technology and products or if the scope of the patent protection obtained is not sufficiently broad, our competitors or other third parties could develop and commercialize technology and products similar or identical to ours, and our ability to successfully develop and commercialize our technology and products may be impaired.

• The continuing outbreak of COVID-19 in the United States and other countries may adversely affect our business and the market price of our common stock.

The foregoing is only a summary of some of our risks. For a more detailed discussion of these and other risks you should consider before making an investment in our common stock, see “Risk Factors.”

Implications of being an emerging growth company

We qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act. As an emerging growth company, we may take advantage of specified reduced disclosure and other requirements that are otherwise applicable generally to public companies, including reduced disclosure about our executive compensation arrangements, exemption from the requirements to hold non-binding advisory votes on executive compensation and golden parachute payments and exemption from the auditor attestation requirement in the assessment of our internal control over financial reporting.

We may take advantage of these exemptions until the last day of the fiscal year following the fifth anniversary of this offering or such earlier time that we are no longer an emerging growth company. We would cease to be an emerging growth company earlier if we have more than $1.07 billion in annual revenue, we have more than $700.0 million in market value of our stock held by non-affiliates (and we have been a public company for at least 12 months and have filed one annual report on Form 10-K) or we issue more than $1.0 billion of non-convertible debt securities over a three-year period. For so long as we remain an emerging growth company, we are permitted, and intend, to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. We may choose to take advantage of some, but not all, of the available exemptions.

In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to

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private companies. We have elected not to “opt out” of such extended transition period, which means that when a standard is issued or revised and it has different application dates for public or private companies, we will adopt the new or revised standard at the time private companies adopt the new or revised standard and will do so until such time that we either (i) irrevocably elect to “opt out” of such extended transition period or (ii) no longer qualify as an emerging growth company. Therefore, the reported results of operations contained in our consolidated financial statements may not be directly comparable to those of other public companies.

Our corporate information

We were formed as a Delaware corporation in June 2012 under the name Cyteir Therapeutics, Inc. Our principal executive office is located at 128 Spring St, Building A, Suite 510, Lexington, MA 02421, and our phone number is 857-285-4140. Our website address is www.cyteir.com. The information contained in or accessible from our website is not incorporated into this prospectus, and you should not consider it part of this prospectus. We have included our website address in this prospectus solely as an inactive textual reference.

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The offering

Common stock offered by us                  shares.

Common stock to be outstanding after this offering                  shares (                 shares if the underwriters exercise their option to purchase additional shares in full).

Underwriters’ option to purchase additional shares of common stock from us We have granted the underwriters an option to purchase up to an aggregate of                  additional shares of common stock from us at the initial public offering price, less the estimated underwriting discounts and commissions, for a period of 30 days after the date of this prospectus.

Use of proceeds We estimate that our net proceeds from the sale of our common stock in this offering will be approximately $             million, assuming an initial public offering price of $         per share, which is the midpoint of the range set forth on the cover page of this prospectus, and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

We currently expect to use the net proceeds from this offering, together with our existing cash and cash equivalents, as follows: approximately $             million to advance the clinical development of CYT-0851; approximately $             million to advance the development of CYT-1853; approximately $             million for other research and development activities; and the remainder, if any, for working capital and other general corporate purposes. See “Use of Proceeds.”

Dividend policy We do not anticipate declaring or paying any cash dividends on our capital stock in the foreseeable future. See “Dividend Policy.”

Risk factors You should carefully read the “Risk Factors” section of this prospectus and the other information included in this prospectus for a discussion of factors that you should consider before deciding to invest in our common stock.

Proposed trading symbol “CYT”

The number of shares of our common stock to be outstanding after this offering is based on 9,298,916 shares of our common stock outstanding as of February 28, 2021, which includes 1,837,573 shares of unvested early exercised stock options, and excludes:

• 8,453,312 shares of common stock issuable upon the exercise of stock options outstanding as of February 28, 2021 under our 2012 Stock Incentive Plan, as amended, or the 2012 Plan, at a weighted average exercise price of $1.20 per share;

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• 9,730,970 shares of common stock available for future issuance as of February 28, 2021 under our 2012 Plan; and

•                  shares of common stock reserved for issuance under our 2021 Equity Incentive Plan, or the 2021 Plan, which will become effective in connection with this offering.

Unless otherwise noted, the information in this prospectus assumes:

• a 1-for-                reverse stock split effected on                , 2021;

• the automatic conversion of all outstanding shares of our convertible preferred stock into an aggregate of 82,802,881 shares of common stock upon the closing of this offering;

• no exercise of the outstanding stock options described above;

• no exercise by the underwriters of their option to purchase additional shares; and

• the filing and effectiveness of our restated certificate of incorporation and the adoption of our amended and restated bylaws upon the closing of this offering.

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Summary consolidated financial data

You should read the following summary consolidated financial data together with the sections titled “Selected Financial Data” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the related notes included elsewhere in this prospectus. We have derived the consolidated statements of operations data for the years ended December 31, 2020 and 2019 from our audited consolidated financial statements included elsewhere in this prospectus. In the opinion of management, the unaudited data reflects all adjustments, consisting only of normal recurring adjustments, necessary for a fair presentation of the financial information in those statements. Our historical results are not necessarily indicative of the results that may be expected in the future.

	Years ended December 31,
	2020			2019
	(in thousands, except share and per share data)
Consolidated Statements of Operations Data:
Grant revenue	$	—		$	8
Operating expenses:
Research and development		16,765			12,768
General and administrative		4,178			3,345
Total operating expenses		20,943			16,113
Loss from operations		(20,943	)		(16,105	)
Total other income		120			1,061
Net loss	$	(20,823	)	$	(15,044	)
Net loss attributable to common stockholders—basic and diluted(1)	$	(20,823	)	$	(15,044	)
Net loss per share—basic and diluted(1)	$	(3.99	)	$	(3.42	)
Weighted average common stock outstanding—basic and diluted(1)		5,217,910			4,397,374
Pro forma net loss per share attributable to common stockholders—basic and diluted(1)	$	(0.31	)
Pro forma weighted average common shares outstanding—basic and diluted(1)		66,235,906

(1) See Note 11 to our audited consolidated financial statements appearing elsewhere in this prospectus for details on the calculation of basic and diluted net loss per share attributable to common stockholders. The unaudited pro forma basic and diluted weighted-average common shares outstanding used in the calculation of unaudited pro forma basic and diluted net loss per share attributable to common stockholders for the year ended December 31, 2020 have been prepared to give effect to the issuance of 21,784,885 shares of our Series C redeemable convertible preferred stock in February 2021 and to give effect, upon a qualified initial public offering, to the automatic conversion of all outstanding shares of redeemable convertible preferred stock into common stock as if the proposed initial public offering had occurred on the later of the beginning of each period or the issuance date of the redeemable convertible preferred stock.

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Risk factors

Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below together with all of the other information contained in this prospectus, including our consolidated financial statements and related notes appearing at the end of this prospectus, before deciding to invest in our common stock. Some of the following risks and uncertainties are, and will be, exacerbated by the COVID-19 pandemic (including any resurgences thereof) and any worsening of the global business and economic environment as a result. If any of the events or developments described below were to occur, our business, prospects, operating results and financial condition could suffer materially, the trading price of our common stock could decline and you could lose all or part of your investment. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently believe to be immaterial may also adversely affect our business.

Risks related to our financial position and need for additional capital

We have a limited operating history and have no products approved for commercial sale, which may make it difficult for you to evaluate our current business and predict our future success and viability.

We are a clinical-stage biopharmaceutical company with a limited operating history. We were incorporated in 2012, and our operations to date have been focused on developing our initial drug candidates, organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, obtaining, maintaining, protecting and enforcing our intellectual property, identifying potential drug candidates, undertaking preclinical and clinical studies and establishing arrangements with third parties for the manufacture of initial quantities of our drug candidates and component materials. We have not yet demonstrated an ability to successfully complete any clinical trials, obtain marketing approvals, manufacture a commercial-scale product or arrange for a third party to do so on our behalf, or conduct sales, marketing and distribution activities necessary for successful product commercialization.

In addition, as a research and development stage business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. If our drug candidates have successful clinical trial results, we will need to transition from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.

We expect our financial condition and results of operations to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.

We have incurred significant losses since inception. We expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

Since our inception, we have devoted all of our efforts to research and development and we have incurred significant operating losses. As of December 31, 2020, we had an accumulated deficit of $49.9 million. To date we have financed our operations primarily through private placements of our preferred stock. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future. The net losses we incur may fluctuate significantly from quarter to quarter. We anticipate that our expenses will increase substantially if and as we:

• advance our lead drug candidate, CYT-0851, through its phase 1/2 clinical trial, into the monotherapy phase 2 expansion portion of the trial and early-stage combination trials;

• advance our preclinical drug candidate CYT-1853 toward an investigational new drug, or IND, application, submission and into clinical trials;

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• continue the preclinical development of additional drug candidates from our current research programs;

• initiate preclinical testing for any new drug candidates we identify and develop;

• pursue potential in-licensing opportunities for preclinical assets;

• obtain, maintain, expand, enforce, defend and protect our trade secrets and intellectual property portfolio;

• hire additional research and development personnel;

• add operational, legal, compliance, financial and management information systems and personnel to support our research, product development and operations as a public company;

• increase our laboratory facilities and office space to support the above;

• operate as a public company;

• expand our research capabilities and operations internationally;

• seek marketing approvals for any of our drug candidates that successfully complete clinical trials; and

• ultimately, establish a sales, marketing, pharmacovigilance, medical affairs, regulatory and distribution infrastructure to commercialize any products for which we may obtain marketing approval.

We expect that it will be many years, if ever, before we have a drug candidate ready for commercialization. To become and remain profitable, we must develop and, either directly or through collaborators, eventually commercialize a medicine or medicines with significant market potential. This will require us to be successful in a range of challenging activities, including identifying drug candidates, completing preclinical testing and clinical trials of drug candidates, obtaining marketing approval for these drug candidates, manufacturing, marketing, and selling those medicines for which we may obtain marketing approval, and satisfying any post-marketing regulatory requirements. We may never succeed in these activities and, even if we do, may never generate revenues that are significant or large enough to achieve profitability. We are unable to predict the extent of any future losses or when we will become profitable, if at all. If we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.

Even if we consummate this offering, we will need substantial additional funding. If we are unable to raise capital when needed, we will be forced to delay, reduce, or eliminate our research and drug development programs or future commercialization efforts.

We expect our expenses to increase in connection with our ongoing activities, particularly as we identify, continue the research and development of, initiate clinical trials of, and seek marketing approval for, our drug candidates. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we will be forced to delay, reduce, or eliminate our research and product development programs or future commercialization efforts.

As of December 31, 2020, our cash and cash equivalents were $10.9 million. In addition, in February 2021 we raised gross proceeds of $80.0 million in our Series C preferred stock financing. We estimate that the net proceeds of this offering will be approximately $                million, assuming an initial public offering price of $                per share, which is the midpoint of the price range set forth on the cover of this prospectus, after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

Additional fundraising efforts, when needed, may divert our management’s attention from their day-to-day activities, which may adversely affect our ability to advance our drug candidates or develop new drug

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candidates. If we raise additional capital through future collaborations, strategic alliances or third-party licensing arrangements, we may have to relinquish certain valuable rights to our intellectual property, future revenue streams, research programs or drug candidates, or grant licenses on terms that may not be favorable to us.

We cannot be certain that additional funding will be available on acceptable terms, or at all. If we are unable to obtain funding on a reasonable and timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs, clinical research, or the commercialization of any drug candidate, or grant rights to develop and market drug candidates that we would otherwise develop and market ourselves. We may be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of operations. Any of the above events could significantly harm our business, prospects, financial condition and results of operations and cause the price of our common stock to decline.

We have never generated revenue from product sales and may never be profitable.

We are currently only in the phase 1/2 clinical trial stage for our most advanced drug candidate, CYT-0851. We expect that it will be many years, if ever, before CYT-0851 or any other drug candidate is ready for commercialization. To become and remain profitable, we must succeed in developing, obtaining marketing approval for and commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including advancing CTY-0851 through clinical development as a monotherapy or in combination with other drugs, completing preclinical testing and clinical trials of our current or future drug candidates, establishing and maintaining arrangements with third parties for the manufacture of clinical supplies of our drug candidates, obtaining marketing approval for our drug candidates and manufacturing, marketing, selling and obtaining reimbursement for any products for which we may obtain marketing approval, and maintaining regulatory requirements while a product is on the market. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability.

Our future ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.

We have incurred substantial net operating losses, or NOLs, during our history and we may not achieve profitability prior to the time that certain of our NOLs expire. U.S. federal and certain state NOLs generated in years beginning after December 31, 2017 are not subject to expiration. Federal NOLs generally may not be carried back to prior taxable years except that, under the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act, federal NOLs generated in 2018, 2019, and 2020 may be carried back to each of the five taxable years preceding the taxable year in which the loss arises. Additionally, for taxable years beginning after December 31, 2020, the deductibility of federal NOLs generated in taxable years beginning after December 31, 2017 will be limited to 80% of our taxable income in such taxable year. NOLs generated in taxable years beginning before January 1, 2018 may still be used to offset future taxable income without regard to the 80% limitation, although they have the potential to expire without being utilized if we do not achieve profitability in the future. To the extent that we continue to generate taxable losses, unused losses will carry forward to offset a portion of future taxable income, if any, subject to expiration in the case of carryforwards generated prior to January 1, 2018. Additionally, we continue to generate business tax credits, including research and development tax credits, which generally may be carried forward to offset a portion of future taxable income, if any, subject to expiration of such credit carryforwards. Futhermore, under Sections 382 and 383 of the Code, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change

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income or taxes may be limited. Our prior equity offerings and other changes in our stock ownership may have resulted in such ownership changes. We may also experience ownership changes in the future as a result of this offering or subsequent shifts in our stock ownership, some of which may be outside of our control. As a result, if we earn net taxable income, our ability to use our pre-change NOLs or other pre-change tax attributes to offset U.S. federal taxable income may be subject to limitations described above, which could potentially result in increased future tax liability to us. There is a risk that under existing tax laws, changes thereto, regulatory changes, or other unforeseen reasons, our existing NOLs or business tax credits could expire or otherwise be unavailable to offset future income tax liabilities. At the state level, there may also be periods during which the use of NOLs or business tax credits is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. For these reasons, we may not be able to realize a tax benefit from the use of our NOLs or tax credits, even if we attain profitability.

Risks related to discovery and development

We have never successfully completed any clinical trials, and we may be unable to do so for any drug candidates we develop.

We have not yet demonstrated an ability to successfully complete any clinical trials, obtain marketing approvals, manufacture a commercial-scale product or arrange for a third party to do so on our behalf, or conduct sales, marketing, pharmacovigilance and distribution activities necessary for successful product commercialization. To date, we only have one drug candidate in clinical development, CYT-0851. We are investigating CYT-0851 in a phase 1/2 trial in adult patients with hematologic malignancies and solid tumors, and have observed encouraging preliminary single agent activity in the dose escalation portion of the trial. If the phase 1/2 data warrant, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors. We also plan to develop CYT-0851 in additional tumor settings as both a monotherapy and in combination with approved cancer therapeutics, and plan to initiate a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021. We do not know whether any of our future clinical trials will begin on time or be completed on schedule, if at all.

If we are required to conduct additional clinical trials or other testing of our drug candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our drug candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may:

• be delayed in obtaining marketing approval for our drug candidates;

• not obtain marketing approval at all;

• obtain approval for indications or patient populations that are not as broad as intended or desired;

• be subject to post-marketing testing requirements; or

• have the product removed from the market after obtaining marketing approval.

Clinical product development is a lengthy and expensive process with an uncertain outcome.

It is impossible to predict when or if any of our drug candidates will prove effective and safe in humans or will receive regulatory approval. The majority of drug candidates in phase 1/2 clinical trials in oncology do not reach regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of any drug candidate, we must complete preclinical studies and then conduct extensive clinical trials to demonstrate the

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safety and efficacy of our drug candidates in humans. Clinical testing is expensive, difficult to design, implement, and execute, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. There is no guarantee that the data or the data quality will meet the standards for regulatory approval. The outcome of preclinical development testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their drug candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their drug candidates. Our preclinical studies and future clinical trials may not be successful.

In addition, we may experience regulatory delays or rejections due to changes in regulatory policy during the period of our drug candidate development. Any such delays could negatively impact our business, financial condition, results of operations and prospects.

We may not be able to file INDs or IND amendments to commence additional clinical trials on the timelines we expect, and even if we are able to, the FDA or a comparable foreign regulatory may not permit us to proceed.

We may not be able to file INDs for any of our drug candidates on the timelines we expect, if at all. Moreover, we cannot be sure that submission of an IND will result in the U.S. Food and Drug Administration, or FDA, allowing further clinical trials to begin, or that, once begun, issues will not arise that require us to suspend or terminate clinical trials. Commencing each of these clinical trials will be subject to finalizing the trial design and selection of relevant endpoints based on discussions with the FDA and other regulatory authorities. Any guidance we receive from the FDA or other regulatory authorities is subject to change. These regulatory authorities could change their position, including, on the acceptability of our trial designs or the clinical endpoints selected, which may require us to complete additional clinical trials or impose stricter approval conditions than we currently expect. Successful completion of our clinical trials is a prerequisite to submitting a new drug application, or NDA, to the FDA for each drug candidate and, consequently, the ultimate approval and commercial marketing of each drug candidate. There is also no assurance that, even if completed, our ongoing or any future clinical trials of drug candidates will be successful or will generate positive clinical data.

We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our drug candidates.

We may experience delays in completing our preclinical studies and initiating or completing clinical trials, and we may experience numerous unforeseen events during, or as a result of, any future clinical trials that we could conduct that could delay or prevent our ability to receive marketing approval or commercialize our drug candidates, including:

• FDA or other regulatory authorities may disagree with the design, protocol or conduct of our clinical trials;

• regulators, institutional review boards, or IRBs, or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

• we may experience delays in reaching, or fail to reach, agreement on acceptable terms with prospective trial sites and prospective contract research organizations, or CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

• clinical trials of our drug candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional preclinical studies or clinical trials or we may decide to abandon product development programs;

• data from one trial may not be reproduced in another study. Contradictory results in clinical trials may result in the requirement for additional trials or the failure to obtain regulatory approval of the drug;

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• the number of patients required for clinical trials of our drug candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials or fail to return for post-treatment follow-up at a higher rate than we anticipate;

• our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, or may deviate from the clinical trial protocol or drop out of the trial, which may require that we add new clinical trial sites or investigators;

• we may elect to, or regulators or IRBs or ethics committees may require us or our investigators to, suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements, a finding that our drug candidates may have undesirable side effects or other unexpected characteristics that expose the participants to unacceptable health risks, or reports may arise from preclinical or clinical testing of other cancer therapies that raise safety or efficacy concerns about our drug candidates;

• the cost of clinical trials of our drug candidates may be greater than we anticipate; and

• the supply or quality of our drug candidates or other materials necessary to conduct clinical trials of our drug candidates may be insufficient or inadequate.

We could encounter delays if a clinical trial is suspended or terminated by us, including based on a recommendation by the Data Safety Monitoring Board, or DSMB, for such trial, by the IRBs of the institutions at which such trials are being conducted or by the FDA or other regulatory authorities. Such authorities may impose such a suspension or termination or clinical hold due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial, superior efficacy of a competing product in development for the same indication, or marketing approval of a superior product that reduces the pool of patients with an unmet need that seek out clinical trials. Many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our drug candidates. Further, the FDA may disagree with our clinical trial design and our interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design for our clinical trials.

Our product development costs will also increase if we experience delays in testing or regulatory approvals. We do not know whether any of our future clinical trials will begin as planned, or whether any of our current or future clinical trials will need to be restructured or will be completed on schedule, if at all. Significant preclinical study or clinical trial delays, including those caused by the COVID-19 pandemic, also could shorten any periods during which we may have the exclusive right to commercialize our drug candidates or allow our competitors to bring products to market before we do and impair our ability to successfully commercialize our drug candidates and may harm our business and results of operations. Any delays in our preclinical or future clinical development programs may harm our business, financial condition and prospects significantly.

If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.

We may not be able to initiate or continue clinical trials for our drug candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In particular, our ability to enroll patients may be significantly delayed by global events such as the COVID-19 pandemic, and we cannot know or predict the extent and scope of such delays at this point.

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We may experience difficulties in identifying and enrolling patients as a result of competition for patients with other ongoing clinical trials. In addition to the competitive trial environment, the eligibility criteria of our planned clinical trials may further limit the pool of available trial participants. Additionally, the process of finding patients may prove costly. We also may not be able to identify, recruit and enroll a sufficient number of patients to complete our clinical trials because of the perceived risks and benefits of the drug candidates under study, the availability and efficacy of competing therapies and clinical trials, the proximity and availability of clinical trial sites for prospective patients, and the patient referral practices of physicians. If patients are unwilling to participate in our studies for any reason or if we are not able to enroll a sufficient number of patients who remain in the study until its conclusion, the timeline for recruiting patients, conducting studies and obtaining regulatory approval for our drug candidates may be delayed.

Patient enrollment may be affected by other factors including:

• the severity of the disease under investigation;

• the eligibility criteria for the clinical trial in question;

• the intensity of study procedures a patient has to go through during study participation;

• the frequency and number of visits required for study participants;

• the number of patients with the disease or condition being studied;

• the approval of new alternative treatments that reduce the number of available study patients;

• the availability of an appropriate patient selection test;

• the clinical trials competing for the same patients;

• the perceived risks and benefits of the drug candidate under study;

• the efforts to facilitate timely enrollment in clinical trials;

• the patient referral practices of physicians;

• our ability to obtain and maintain patient consents;

• the ability to monitor patients adequately during and after treatment, which may be worsened by pandemics such as COVID-19;

• the risk that patients enrolled in clinical trials will drop out of the clinical trials before completion of their treatment or study follow-up visits, especially during a pandemic such as COVID-19;

• the proximity and availability of clinical trial sites for prospective patients; and

• factors we may not be able to control, such as current or potential future global health crises that may limit patients, principal investigators or staff or clinical site availability (for example, the ongoing COVID-19 pandemic).

Interim, “top-line” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publish interim, top-line or preliminary data from our clinical trials. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as

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patient enrollment continues and more patient data become available. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, interim, top-line and preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our business prospects.

Positive results from the clinical trials and preclinical studies of our drug candidates are not necessarily predictive of the results of later clinical trials or preclinical studies. If we cannot replicate the positive results from our clinical trials and preclinical studies of our drug candidates in our later clinical trials preclinical studies, we may be unable to successfully develop, obtain regulatory approval for and commercialize our drug candidates.

Any positive results from clinical trials and preclinical studies of our drug candidates may not necessarily be predictive of the results from later clinical trials and preclinical studies. Similarly, even if we are able to complete the planned clinical trials and preclinical studies of our drug candidates according to our current development timeline, the positive results from such trials and studies may not be replicated in subsequent trials and studies.

Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials after achieving positive results in early-stage development, and we cannot be certain that we will not face similar setbacks. These setbacks have been caused by, among other things, preclinical and other nonclinical findings made while clinical trials were underway, or safety or efficacy observations made in preclinical studies and clinical trials, including previously unreported adverse events. Moreover, preclinical, nonclinical and clinical data are often susceptible to varying interpretations and analyses and many companies that believed their drug candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain approval from the FDA or other regulatory authorities.

Our planned clinical trials may reveal significant adverse events not seen in our preclinical or nonclinical studies and may result in a safety profile that could inhibit regulatory approval or market acceptance of our drug candidates.

Before obtaining regulatory approvals for the commercial sale of any products, we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our drug candidates are both safe and effective for use in each target indication. Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of our drug candidates may not be predictive of the results of later-stage clinical trials. In addition, initial success in clinical trials may not be indicative of results obtained when such trials are completed. There is typically an extremely high rate of attrition from the failure of drug candidates proceeding through clinical trials. Drug candidates in later stages of clinical trials also may fail to show the desired safety and efficacy profile despite having progressed through nonclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or unacceptable safety issues, notwithstanding promising results in earlier trials. Most drug candidates that commence clinical trials are never approved as products and there can be no assurance that any of our current or future clinical trials will ultimately be successful or support further clinical development of any of our drug candidates.

We may develop future drug candidates in combination with one or more cancer therapies. The uncertainty resulting from the use of our drug candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials. For example, our lead drug candidate, CYT-0851, has been shown in in vitro experiments to inhibit the activity of a human liver enzyme that metabolizes other drugs, including some anti-cancer drugs.

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As is the case with many treatments for cancer, it is possible that there may be side effects associated with the use of our drug candidates. Our clinical trial includes cancer patients who are very sick and whose health is deteriorating, and we expect that additional clinical trials of our other drug candidates will include similar patients with deteriorating health. It is possible that some of these patients may experience adverse side effects, and that some patients may die during our clinical trials for various reasons, including as a result of receiving our drug candidates, because the patient’s disease is too advanced, or because the patient experiences medical problems that may not be related to our drug candidate. Even if the deaths are not related to our drug candidates, the deaths could affect perceptions regarding the safety of our drug candidate. In addition, due to the lack of a clear mechanism of action with respect to our drug candidates, we may find it difficult or impossible to mitigate against any adverse side effects resulting from toxicity, which could lead to developmental delays, added costs from increased safety monitoring and decreased study enrollment and difficulties in the identification of patient populations likely to benefit from our drug candidates, which could in turn lead to reduced efficacy and ultimately impact our ability to receive regulatory approval.

If significant adverse events or other side effects are observed in any of our current or future clinical trials, we may have difficulty recruiting patients into our clinical trials, patients may drop out of our trials, or we may be required to abandon the trials or our development efforts of one or more drug candidates altogether. We, the FDA or other applicable regulatory authorities, or an IRB may suspend or terminate clinical trials of a drug candidate at any time for various reasons, including a belief that subjects in such trials are being exposed to unacceptable health risks or adverse side effects. Some potential therapeutics developed in the biotechnology industry that initially showed therapeutic promise in early-stage trials have later been found to cause side effects that prevented their further development. Even if the side effects do not preclude the product from obtaining or maintaining marketing approval, undesirable side effects may inhibit market acceptance of the approved product due to its tolerability versus other therapies. Any of these developments could materially harm our business, financial condition and prospects.

We intend to develop CYT-0851, and potentially future drug candidates, for use in combination with other therapies, which exposes us to additional risks.

We intend to develop CYT-0851, and potentially future drug candidates, for use in combination with one or more PARP inhibitors, chemotherapies or other oncology treatments. Combination therapies are commonly used for the treatment of cancer, and we would be subject to similar risks if we develop any of our drug candidates for use in combination with other drugs or for indications other than cancer. Even if any drug candidate we develop were to receive marketing approval or be commercialized for use in combination with other existing therapies, we would continue to bear the risks that the FDA or similar foreign regulatory authorities could revoke approval of the therapy used in combination with our drug candidate or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies. This could result in our own products being removed from the market or being less successful commercially.

We may also evaluate future drug candidates in combination with one or more other cancer therapies that have not yet been approved for marketing by the FDA or similar foreign regulatory authorities. We will not be able to market and sell any drug candidate we develop in combination with any such unapproved cancer therapies that do not ultimately obtain marketing approval. If the FDA or similar foreign regulatory authorities do not approve these other drugs or revoke their approval of, or if safety, efficacy, manufacturing, or supply issues arise with, the drugs we choose to evaluate in combination with our drug candidates, we may be unable to obtain approval of or market our drug candidates.

If the FDA or comparable foreign regulatory authorities do not approve or revoke their approval of, or if safety, efficacy, manufacturing, or supply issues arise with, therapies we choose to evaluate in combination with any of our drug candidates, we may be unable to obtain regulatory approval of or to commercialize such drug candidates in combination with these therapies.

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If we are unable to successfully develop and commercialize companion diagnostic tests for our drug candidates, or experience significant delays in doing so, we may not realize the full commercial potential of our drug candidates.

Because predictive biomarkers may be used to select patients for our drug candidates, we believe that our success may depend, in part, on the development and commercialization of companion diagnostic tests. While we were granted an Investigational Device Exemption for use of an investigational companion diagnostic in our phase 1/2 clinical trial of CYT-0851, we have no experience in the development and commercialization of companion diagnostic tests and may not be successful in developing and commercializing appropriate companion diagnostic tests to pair with CYT-0851 or any of our drug candidates that receive marketing approval. Companion diagnostic tests are subject to regulation by the FDA and similar regulatory authorities outside the United States as medical devices and require separate regulatory approval prior to commercialization. We may encounter difficulties in identifying biomarkers that are predictive of response to our therapies or may never identify a biomarker at all. We may not be able to develop assays that consistently measure our biomarkers in clinical trials and some biomarkers may not be able to be measured in certain tumor types precluding development in those indications. Even if our biomarkers prove effective for patient selection we may still encounter difficulties developing and obtaining regulatory approval for the companion diagnostic tests, including issues relating to selectivity/specificity, analytical validation, reproducibility, or clinical validation. While our drug candidates will have their marketing applications reviewed by FDA’s Center for Drug Evaluation and Research, or CDER, companion diagnostics require separate marketing applications under the primary jurisdiction of FDA’s Center for Devices and Radiological Health, or CDRH. This parallel jurisdiction and separate marketing applications could result in coordination issues, require additional time and effort, or result in delays or failure to obtain marketing approval for either the companion diagnostic or related drug indications.

Any failure to develop or obtain regulatory approval of the companion diagnostic tests could delay or prevent approval of our drug candidates. If we, or any third parties that we may in the future engage to assist us, are unable to successfully develop and commercialize companion diagnostic tests for our drug candidates, or experience delays in doing so:

• the development of our drug candidates may be adversely affected if we are unable to appropriately select patients for enrollment in our clinical trials;

• our drug candidates may not receive marketing approval if safe and effective use of a therapeutic drug candidate depends on an in vitro diagnostic; or

• we may not realize the full commercial potential of any drug candidates that receive marketing approval if, among other reasons, we are unable to appropriately select patients who are likely to benefit from treatment with our drugs.

If any of these events were to occur, our business would be materially harmed.

Synthetic lethality represents an emerging class of precision medicine targets, and negative perceptions of the efficacy, safety or tolerability of this class of targets, including any that we develop, could adversely affect our ability to conduct our business, advance our drug candidates or obtain regulatory approvals.

Aside from PARP inhibitors, such as Lynparza, Rubraca, Zejula and Talzenna, no synthetically lethal small molecule inhibitor therapeutics have been approved to date by the FDA or other comparable regulators. Adverse events in future clinical trials of our drug candidates or in clinical trials of others developing similar products and the resulting publicity, as well as any other adverse events in the field of synthetic lethality, or other products that are perceived to be similar to synthetic lethality, such as those related to gene therapy or

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gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and CROs in our drug candidates, and less demand for any product that we may develop. Our synthetic lethality drug candidates could result in a greater quantity of reportable adverse events or other reportable negative clinical outcomes, manufacturing reportable events or material clinical events that could lead to clinical delays or holds by the FDA or applicable regulatory authority or other clinical delays, any of which could negatively impact the perception of one or more of our synthetic lethality programs, as well as our business as a whole. In addition, responses by U.S. federal or foreign governments to negative public perception may result in new legislation or regulations that could limit our ability to develop any drug candidates or commercialize any approved products, obtain or maintain regulatory approval, or otherwise achieve profitability. More restrictive statutory regimes, government regulations, or negative public opinion would have an adverse effect on our business, financial condition, results of operations, and prospects, and may delay or impair the development of our drug candidates and commercialization of any approved products or demand for any products we may develop.

We may in the future conduct clinical trials for our drug candidates outside the United States, and the FDA and similar foreign regulatory authorities may not accept data from such trials.

We may in the future choose to conduct additional clinical trials outside the United States. The acceptance of trial data from clinical trials conducted outside the United States by the FDA may be subject to certain conditions. In cases where data from clinical trials conducted outside the United States are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the United States population and United States medical practice; (ii) the trials were performed in accordance with Good Clinical Practices, or GCPs, and by clinical investigators of recognized competence and (iii) the data may be considered valid without the need for an on-site inspection by the FDA or, if the FDA considers such an inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory bodies have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any similar foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction. If the FDA or any similar foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in our drug candidates not receiving approval or clearance for commercialization in the applicable jurisdiction.

The market opportunities for certain of our drug candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small, and the incidence and prevalence for target patient populations of our drug candidates have not been established with precision. If the market opportunities for our drug candidates are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the patient population, our revenue and ability to achieve profitability will be materially and adversely affected.

Cancer therapies are sometimes characterized as first line, second line or third line, and the FDA often approves new therapies initially only for later line use where there are not good therapeutic alternatives. When cancers are detected and require systemic treatment, these are treated with the first line therapy. This generally consists of chemotherapy, radiation, antibody drugs, tumor targeted small molecules, or a combination of these. In addition, sometimes a bone marrow transplantation may also be used. If the patient’s cancer progresses or relapses, then they are given a second line or third line therapy, which can consist of more chemotherapy, radiation, antibody drugs, tumor targeted small molecules, or a combination of these, or bone marrow transplant. Generally, as patients progress through lines of therapy, the number of patients deriving

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benefit decreases, as does the time that the treatment controls their cancer. We are targeting a wide range of cancer populations in our clinical trials of CYT-0851; the line of therapy we will pursue for potential registration for CYT-0851 will depend on the target disease indication and the size of benefit observed for patients receiving CYT-0851, but in most cases is likely to be positioned initially as a second or later line therapy.

We are currently evaluating the safety and tolerability of CYT-0851 in a phase 1/2 dose escalation study in patients with relapsed and/or refractory B-cell malignancies and advanced solid tumors and plan to study combinations in the future. We believe that CYT-0851 has the potential to be approved in multiple monotherapy and combination therapy settings for both hematologic malignancies and solid tumors.

In the future, if CYT-0851 advances to earlier lines of treatment as either a monotherapy or as a combination therapy, it could potentially address additional patients annually in the U.S. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with CYT-0851, or any of our drug candidates, are based on estimates.

The total addressable market opportunity will ultimately depend upon, among other things, the treatment criteria included in the final label. Even if our drug candidates are approved for sale for these indications, acceptance by the medical community may be lower than estimated and patient access, product pricing and reimbursement may hinder sales and lead to lower sales. The number of patients with cancers and solid tumors may turn out to be lower than expected, patients may not be otherwise amenable to treatment with our products, or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business. We may not be successful in our efforts to identify additional drug candidates. Due to our limited resources and access to capital, we must prioritize development of certain drug candidates, which may prove to be the wrong choice and may adversely affect our business.

Although we intend to explore other therapeutic opportunities in addition to the drug candidates that we are currently developing, we may fail to identify viable new drug candidates for clinical development for a number of reasons. If we fail to identify additional potential drug candidates, our business could be materially harmed.

In addition to our drug candidates that are currently under development, we will continue to build and direct our DDR biology expertise and discovery and translational research capabilities and capacity to generate additional discovery programs. We currently have one undisclosed target program that is undergoing chemical series assay testing and medicinal chemistry. In addition, we have another program that is currently in the target assessment stage and are screening external preclinical-stage programs for in-licensing. Research programs to identify new disease targets and drug candidates require substantial technical, financial and human resources whether or not they are ultimately successful. There can be no assurance that we will find potential additional drug candidates using this approach or that such potential drug candidates will be clinically validated. Our research programs may initially show promise in identifying potential indications and/or drug candidates, yet fail to yield results for clinical development for a number of reasons, including:

• the research methodology used may not be successful in identifying potential indications and/or drug candidates;

• potential drug candidates may, after further study, be shown to have harmful adverse effects or other characteristics that indicate they are unlikely to be effective products; or

• it may take greater human and financial resources than we will possess to identify additional therapeutic opportunities for our drug candidates or to develop suitable potential drug candidates through internal research programs, thereby limiting our ability to develop, diversify and expand our product portfolio.

Because we have limited financial and human resources, we intend to initially focus on research programs and drug candidates for a limited set of indications. As a result, we may forgo or delay pursuit of opportunities with

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other drug candidates or for other indications that later prove to have greater commercial potential or a greater likelihood of success. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities.

Accordingly, there can be no assurance that we will ever be able to identify additional therapeutic opportunities for our drug candidates or to develop suitable potential drug candidates through internal research programs, which could materially adversely affect our future growth and prospects. We may focus our efforts and resources on potential drug candidates or other potential programs that ultimately prove to be unsuccessful.

If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals for our drug candidates, we will not be able to commercialize, or will be delayed in commercializing, our drug candidates, and our ability to generate revenue will be materially impaired.

Our drug candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable authorities in other countries. Before we can commercialize any of our drug candidates, we must obtain marketing approval. Currently, all of our drug candidates are in development, and we have not received approval to market any of our drug candidates from regulatory authorities in any jurisdiction. It is possible that our drug candidates, including any drug candidates we may seek to develop in the future, will never obtain regulatory approval. We have only limited experience in filing and supporting the applications necessary to gain regulatory approvals and expect to rely on third-party CROs and/or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the drug candidate’s safety and efficacy. It requires quality assurance and control systems that meet regulatory standards, and publishing know-how to submit the regulatory applications and gain approval. We have limited experience building quality systems and publishing new drug applications and will rely on third-party CROs and vendors to establish these controls and systems. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Our drug candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use. In addition, regulatory authorities may find fault with our manufacturing processes or facilities or that of third-party contract manufacturers. We may also face greater than expected difficulty in manufacturing our drug candidates.

The process of obtaining regulatory approvals, both in the United States and abroad, is expensive and often takes many years. If the FDA or a comparable foreign regulatory authority requires that we perform additional preclinical or clinical trials, or manufacturing changes, approval, if obtained at all, may be delayed. The length of such a delay varies substantially based upon a variety of factors, including the type, complexity and novelty of the drug candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted application may cause delays in the approval or rejection of an application. The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies or make manufacturing changes. Our drug candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following:

• the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;

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• we may not be able to enroll a sufficient number of patients in our clinical studies;

• we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a drug candidate is safe and effective for its proposed indication or a related companion diagnostic is suitable to identify appropriate patient populations;

• the results of clinical trials may not meet the level of statistical significance or the degree of benefit required by the FDA or comparable foreign regulatory authorities for approval;

• we may be unable to demonstrate that a drug candidate’s clinical and other benefits outweigh its safety risks;

• the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

• the data collected from clinical trials of our drug candidates may not be sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere;

• the FDA or comparable foreign regulatory authorities may fail to approve the purity of our product;

• the FDA or comparable foreign regulatory authorities may find deficiencies with or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies;

• the FDA or comparable foreign regulatory authorities may fail to accept the preclinical pharmacology, safety and toxicology evaluation as adequate to support approval of the drugs; and

• the approval policies, the interpretation of the regulatory approval guidelines by the reviewers, or regulations of the FDA or comparable foreign regulatory authorities may significantly change such that our clinical and non-clinical data are insufficient for approval.

Even if we were to obtain approval, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, or may not allow us to present all safety and efficacy data in the drug label, thereby narrowing the commercial potential of the drug candidate. In addition, regulatory authorities may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our drug candidates.

If we experience delays in obtaining approval or if we fail to obtain approval of our drug candidates, the commercial prospects for our drug candidates may be harmed and our ability to generate revenues will be materially impaired.

While we continue to pursue a further understanding of the molecular binding mechanism of our drug candidates, we do not currently know, and might never know, the precise mechanism of action of our inhibitors of RAD51-mediated HR.

Our lead candidates, CYT-0851 and CYT-1853, were discovered from a phenotypic screen and the exact mechanism of action by which they function is not currently known and may never be known. While this knowledge is not required for regulatory approval, the lack thereof could still pose significant development challenges that result in delays in our development or our ability to commercialize our products, including difficulties managing any unexpected toxicities should they arise. Without a clear mechanism of action, we may find it difficult or impossible to mitigate against any adverse side effects resulting from toxicity, which could lead to developmental delays, added costs from increased safety monitoring and decreased study enrollment.

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Our business substantially depends upon the successful development of drug candidates generated through the application of our platform, and in particular, our lead drug candidate, CYT-0851. If we are unable to obtain regulatory approval for, and successfully commercialize, products developed through the application of our platform, our business may be materially harmed.

Our lead drug candidate, CYT-0851, was developed through the application of our platform. All of our drug candidates to date were derived based on the same principle of synthetic lethality. As such, negative results in the development of CYT-0851 may also impact our ability to obtain regulatory approval for our other drug candidates, either at all or within anticipated timeframes because, although other drug candidates may target different indications, the underlying technology platform, manufacturing process and development process is the same for all of our drug candidates. Accordingly, a failure in any one program may decrease trust in our technology and affect the ability to obtain regulatory approval to continue or conduct clinical programs for other drug candidates. If CYT-0851 shows unexpected adverse events or a lack of efficacy in the indications we intend to treat, or if we experience other regulatory or developmental issues, our development plans and business could be significantly harmed.

Risks related to the commercialization of our drug candidates

We face substantial competition, which may result in others developing or commercializing drugs before or more successfully than us.

The biopharmaceutical industry is characterized by intense competition and rapid innovation. Our competitors may be able to develop other compounds or drugs that are able to achieve similar or better results. Our potential competitors include major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies and universities and other research institutions. Many of our competitors have substantially greater financial, technical and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations and well-established sales forces. Smaller or early-stage companies may also prove to be significant competitors, particularly as they develop novel approaches to treating disease indications that our drug candidates are also focused on treating. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel therapeutics or to in-license novel therapeutics that could make the drug candidates that we develop obsolete. Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated in our competitors. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors, either alone or with collaborative partners, may succeed in developing, acquiring or licensing on an exclusive basis drug or biologic products that are more effective, safer, more easily commercialized or less costly than our drug candidates or may develop proprietary technologies or secure patent protection that we may need for the development of our technologies and products. We believe the key competitive factors that will affect the development and commercial success of our drug candidates are efficacy, safety, tolerability, reliability, convenience of use, price and reimbursement.

We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of precision oncology therapies for patients with genetically-defined cancers. Several biopharmaceutical companies, including Loxo Oncology, Inc. (recently acquired by Eli Lilly and Company), Blueprint Medicines Corporation, Agios Pharmaceuticals, Inc., SpringWorks Therapeutics, Inc., Black Diamond Therapeutics, Inc., Deciphera Pharmaceuticals, Inc., Turning Point Therapeutics, Inc., and Repare Therapeutics, Inc., are developing precision oncology medicines. In addition, we may face competition from companies developing drug candidates that are based on synthetic lethality, including AstraZeneca, GlaxoSmithKline, Pfizer, Bayer, Merck Serono, Artios Pharma Ltd. and IDEAYA Biosciences, Inc.

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We anticipate that we will continue to face intense and increasing competition as new treatments enter the market and advanced technologies become available. There can be no assurance that our competitors are not currently developing, or will not in the future develop, products that are equally or more effective or are more economically attractive than any of our current or future drug candidates. Competing products may gain faster or greater market acceptance than our products, if any, and medical advances or rapid technological development by competitors may result in our drug candidates becoming non-competitive or obsolete before we are able to recover our research and development and commercialization expenses. If we or our drug candidates do not compete effectively, it may have a material adverse effect on our business, financial condition and results of operations.

We may expend our limited resources to pursue a particular drug candidate or indication and fail to capitalize on drug candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Because we have limited financial and managerial resources, we focus on research programs and drug candidates that we identify for specific indications among many potential options. As a result, we may forego or delay pursuit of opportunities with other drug candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and drug candidates for specific indications may not yield any commercially viable medicines. If we do not accurately evaluate the commercial potential or target market for a particular drug candidate, we may relinquish valuable rights to that drug candidate through collaboration, licensing, or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such drug candidate. Any such event could have a material adverse effect on our business, financial condition, results of operations, and prospects.

We currently have no marketing and sales organization and have no experience as a company in marketing products. If we are unable to establish marketing and sales capabilities or enter into agreements with third parties to market and sell our drug candidates, if approved, we may not be able to generate product revenue.

We currently have no sales, marketing or distribution capabilities and have no experience in marketing products. We intend to develop an in-house marketing organization and sales force, which will require significant capital expenditures, management resources and time. We will have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train and retain marketing and sales personnel.

If we are unable or decide not to establish internal sales, marketing and distribution capabilities, we will pursue arrangements with third-party sales, marketing, and distribution collaborators regarding the sales and marketing of our products, if approved. However, there can be no assurance that we will be able to establish or maintain such arrangements on favorable terms or if at all, or if we are able to do so, that these third-party arrangements will provide effective sales forces or marketing and distribution capabilities. Any revenue we receive will depend upon the efforts of such third parties, which may not be successful. We may have little or no control over the marketing and sales efforts of such third parties and our revenue from product sales may be lower than if we had commercialized our drug candidates ourselves. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our drug candidates.

There can be no assurance that we will be able to develop in-house sales and distribution capabilities or establish or maintain relationships with third-party collaborators to commercialize any product in the United States or overseas.

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Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.

Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. A severe or prolonged economic downturn, or additional global financial crises, could result in a variety of risks to our business, including weakened demand for our drug candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all. For example, the global financial crisis caused extreme volatility and disruptions in the capital and credit markets. Similarly, the recent significant volatility associated with the ongoing COVID-19 pandemic has caused significant instability and disruptions in the capital and credit markets. A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.

Risks related to employee matters, managing growth and information technology

We are highly dependent on our key personnel. If we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.

We are highly dependent on Markus Renschler, M.D., our President and Chief Executive Officer. In addition, the loss of the services of any of our executive officers, other key employees and other scientific and medical advisors, and an inability to find suitable replacements could result in delays in product development and harm our business.

Despite our efforts to retain Dr. Renschler and other valuable employees, members of our management, scientific and development teams may terminate their employment with us on short notice. Although we have employment agreements with our key employees, these employment agreements provide for at-will employment, which means that any of our employees could leave our employment at any time, with or without notice.

We will need to grow the size of our organization, and we may experience difficulties in achieving or managing this growth.

As of February 28, 2021, we had 25 full-time employees. We intend to hire new employees to assume activities and responsibilities within the company, including conducting our research and performing development activities in the future.

Our ability to compete in the highly competitive biotechnology and pharmaceutical industries depends upon our ability to attract and retain highly qualified managerial, scientific and medical personnel. We conduct our operations at our facilities in Lexington, Massachusetts. The Massachusetts region is headquarters to many other biopharmaceutical companies and many academic and research institutions. Competition for skilled personnel in our market is intense and may limit our ability to hire and retain highly qualified personnel on acceptable terms or at all. Changes to U.S. immigration and work authorization laws and regulations, including those that restrain the flow of scientific and professional talent, can be significantly affected by political forces and levels of economic activity. Our business may be materially adversely affected if legislative or administrative changes to immigration or visa laws and regulations impair our hiring processes and goals or projects involving personnel who are not U.S. citizens.

Any delay or disruption in hiring such new employees could result in delays in our research and development activities and would harm our business. We rely on third-party recruiters to help us fill the positions. The recruiters may not perform which may delay hiring. As our development and commercialization plans and

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strategies develop, and as we transition into operating as a public company, we expect to need additional managerial, operational, sales, marketing, quality, regulatory affairs, financial and other personnel, as well as additional facilities to expand our operations.

If we are not able to effectively expand our organization by hiring new employees and expanding our groups of consultants and contractors, or we are not able to effectively build out new facilities to accommodate this expansion, we may not be able to successfully implement the tasks necessary to further develop and commercialize our drug candidates and, accordingly, may not achieve our research, development and commercialization goals.

Our internal computer systems, or those used by our third-party CROs or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of the development programs of our drug candidates.

Despite the implementation of security measures, our internal computer systems and those of our current and future CROs and other vendors, contractors and consultants are vulnerable to damage from data breaches, computer viruses, cybersecurity threats (such as denial-of-service attacks, cyber-attacks, cyber-intrusions, hacking, phishing and other social engineering attacks), unauthorized access or use, natural disasters, terrorism, war and telecommunication and electrical failures. Because the techniques used to obtain unauthorized access, disable or degrade service or sabotage systems change frequently and often are not recognized until launched against a target, we and our vendors may be unable to anticipate these techniques or to implement adequate preventative measures. As we become more dependent on information technologies to conduct our operations, such incidents, including deliberate attacks and attempts to gain unauthorized access to such computer systems and networks, may increase in frequency and sophistication. Further, we do not have any control over the operations of the facilities or technology of our vendors, including any vendors that collect, transmit, store and otherwise process personal information on our behalf. Our systems, servers and platforms and those of our vendors may be vulnerable to computer viruses or physical or electronic break-ins that our or their security measures may not detect. For example, while we have not experienced any such material system failure or security breach at our company to date, one of our clinical trial CROs had an incident but had adequate mechanisms to recover all of our data. If such a security breach were to occur and cause interruptions in our operations or the operations of one of our CROs or vendors, or result in the unauthorized disclosure of or access to personally identifiable information or individually protected health information, it could result in a material disruption of our development programs and our business operations. For example, the loss of data from completed or future preclinical studies and clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Likewise, we rely on third parties for the manufacture of our drug candidates and to conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our or our vendors’ data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and commercialization of our drug candidates could be delayed. We may also need to expend significant resources to protect against security breaches or to mitigate the impact of any such breaches. There can be no assurance that we or our third-party providers will be successful in preventing security breaches or successfully mitigating their effects.

Any security breach or other incident, whether real or perceived, that results in a loss of or accidental, unlawful or unauthorized access to, use of, release of or other processing of personal, proprietary or other sensitive information could impact our reputation, cause us to incur significant liability and costs, including legal expenses, fines and penalties for any noncompliance with any privacy and security laws, harm customer confidence, hurt our expansion into new markets, cause us to incur remediation costs or cause us to lose existing customers. We do not currently maintain cybersecurity insurance, and any insurance we may maintain

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against the risk of this type of loss in the future may not be sufficient to cover actual losses, or may not apply to the circumstances relating to any particular loss.

Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, the FDA’s ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies may also slow the time necessary for new drugs or modifications to approved drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years, including for 35 days beginning on December 22, 2018, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities.

Separately, in response to the COVID-19 pandemic, on March 10, 2020 the FDA announced its intention to postpone most foreign inspections of manufacturing facilities and products, and subsequently, on March 18, 2020, the FDA announced its intention to temporarily postpone routine surveillance inspections of domestic manufacturing facilities and provided guidance regarding the conduct of clinical trials, which has since been further updated and is being refreshed on a periodic basis. As of June 23, 2020, the FDA noted it was continuing to ensure timely reviews of applications for medical products during the COVID-19 pandemic in line with its user fee performance goals and conducting “mission–critical” domestic and foreign inspections to ensure compliance of manufacturing facilities with FDA quality standards.

Most recently, as of July 2020, utilizing a rating system to assist in determining when and where it is safest to conduct such inspections based on data about the virus’s trajectory in a given state and locality and the rules and guidelines that are put in place by state and local governments, the FDA is either continuing to, on a case-by-case basis, conduct only “mission-critical” inspections, or, where possible to do so safely, resuming prioritized domestic inspections, which generally include pre-approval inspections. Foreign pre-approval inspections that are not deemed mission-critical remain postponed, while those deemed mission-critical will be considered for inspection on a case-by-case basis. The FDA will use similar data to inform resumption of prioritized operations abroad as it becomes feasible and advisable to do so. The FDA’s assessment of whether an inspection is mission-critical considers many factors related to the public health benefit of U.S. patients having access to the product subject to inspection, including whether the products are used to diagnose, treat, or prevent a serious disease or medical condition for which there is no other appropriate substitute. Both for-cause and pre-approval inspections can be deemed mission-critical. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic. If a prolonged government shutdown occurs, or if global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

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The continuing outbreak of COVID-19 in the United States and other countries may adversely affect our business and the market price of our common stock.

The recent COVID-19 pandemic is impacting worldwide economic activity, particularly economic activity in the United States, and poses the risk that we or our employees, contractors, suppliers, or other partners may be prevented or delayed from conducting business activities for an indefinite period of time, including due to shutdowns that may be requested or mandated by governmental authorities. The ongoing COVID-19 pandemic and the measures taken by the governments of countries affected by it could disrupt the supply chain and the manufacture or shipment of both drug substance and finished drug product for our drug candidates for preclinical testing or clinical trials, cause diversion of healthcare resources away from the conduct of preclinical and clinical trial matters to focus on pandemic concerns, limit travel in a manner that interrupts key trial activities, such as trial site initiations and monitoring, delay regulatory filings with regulatory agencies in affected areas or adversely affect our ability to obtain regulatory approvals. These disruptions could also affect other facets of our business, including but not limited to:

• our ability to recruit employees from outside of the United States;

• the ability of our CROs to conduct clinical trials and preclinical studies in countries outside of the United States;

• our ability to important materials from outside of the United States, including raw materials required to manufacture our drug;

• our ability to export materials to our CROs and other third-parties located outside of the United States;

• our ability to identify suitable clinical sites or open those sites for enrollment due to competing business needs;

• our ability to enroll patients due to their fear of coming into medical facilities and their perceived risk of becoming infected at such facilities; and

• our ability to monitor the clinical data generated at clinical sites, required for completion of clinical trials.

The COVID-19 outbreak and mitigation measures also may have an adverse impact on global economic conditions, which could adversely impact our business, financial condition or results of operations. Additionally, the COVID-19 outbreak has resulted in significant financial market volatility and uncertainty. A continuation or worsening of the levels of market disruption and volatility seen in the recent past as a result of the COVID-19 outbreak could have an adverse effect on our ability to access capital and on the market price of our common stock.

Risks related to our intellectual property

If we are unable to adequately protect and enforce our intellectual property or obtain and maintain patent protection for our technology and products or if the scope of the patent protection obtained is not sufficiently broad, our competitors or other third parties could develop and commercialize technology and products similar or identical to ours, and our ability to successfully develop and commercialize our technology and products may be impaired.

Our commercial success will depend in part on our ability and the ability of our licensors and collaborators to obtain, maintain, enforce and protect proprietary or intellectual property protection in the United States and other countries for our drug candidates and our core technologies. We rely on patent protection, trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and intellectual property position.

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We seek to protect our proprietary drug candidates by filing patent applications in the United States and abroad related to our drug candidates and other proprietary technologies that are important to our business. If we or our licensors are unable to obtain, maintain, protect or enforce patent protection with respect to our current and future drug candidates, competitors and other third parties could develop and commercialize products similar or identical to ours, and our ability to successfully commercialize our current drug candidates and other drug candidates that we may pursue may be impaired. As a result, our business, financial condition, results of operations and prospects could be materially harmed.

The degree of patent protection we require to successfully commercialize our drug candidates may be unavailable or severely limited in some cases and may not adequately protect our rights or permit us to gain or keep any competitive advantage. For example, we do not currently own or in-license any issued patents covering our CYT-1853 drug candidate. We cannot provide any assurances that any of our pending patent applications will issue, or that any of our patent applications that have matured or may mature into issued patents will include claims with a scope sufficient to protect CYT-0851, CYT-1853 or our other current or future drug candidates. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. Furthermore, patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional or international patent application filing date. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Given the amount of time required for the development, testing and regulatory review of new drug candidates, patents protecting such drug candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with adequate and continuing patent protection sufficient to exclude others from commercializing products similar or identical to our drug candidates, including generic versions of such drugs.

Other parties have developed technologies that may be related or competitive to our own, and such parties may have filed or may file patent applications, or may have received or may receive patents, claiming inventions that may overlap or conflict with those claimed in our owned or in-licensed patent applications, in either case that they may rely upon to dominate our patent position in the market. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing or until issuance or, in some cases, not published at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our owned or licensed pending patent applications, or that we were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights cannot be predicted with any certainty.

In addition, the patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. Further, with respect to many of the pending patent applications covering our drug candidates, prosecution has yet to commence. Patent prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the U.S. Patent and Trademark Office, or USPTO, have often been significantly narrowed by the time they issue, if at all. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection.

Even if we acquire patent protection that we expect should enable us to maintain a competitive advantage, third parties may challenge the validity, enforceability or scope thereof, which may result in such patents being narrowed, invalidated or held unenforceable. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad. For example, we may be subject to a third-party submission of prior art to the USPTO challenging the priority of an invention claimed within one of our patents, which submissions may

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also be made prior to a patent’s issuance, precluding the granting of any of our pending patent applications. We may become involved in opposition, derivation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others from whom we have obtained licenses to such rights. Competitors or other third parties may claim that they invented the inventions claimed in our issued patents or patent applications prior to us, or may file patent applications before we do. Competitors or other third parties may also claim that we are infringing, misappropriating or otherwise violating their patents or other intellectual property and proprietary rights and that we therefore cannot practice our technology as claimed under our patents, if issued. Competitors or other third parties may also contest our patents, if issued, by showing the patent examiner that the invention was not original, was not novel or was obvious. In litigation, a competitor or other third party could claim that our patents, if issued, are not valid for a number of reasons. If a court agrees, we would lose our rights to those challenged patents.

In addition, we may in the future be subject to claims by our former employees, consultants, advisors or independent contractors asserting an ownership right in our patents, patent applications or technologies, as a result of the work they performed on our behalf. Although we generally require all of our employees, consultants and advisors and any other third parties who have access to our proprietary know-how, information or technology to assign or grant similar rights to their inventions to us, we cannot be certain that we have executed such agreements with all parties who may have contributed to our intellectual property, nor can we be certain that our agreements with such parties will be upheld in the face of a potential challenge, or that they will not be breached, for which we may not have an adequate remedy.

An adverse determination in any such submission or proceeding may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, without payment to us, or could limit the duration of the patent protection covering our technology and drug candidates. Such challenges may also result in our inability to manufacture or commercialize our drug candidates without infringing, misappropriating or otherwise violating third party patent or other intellectual property rights or require us to license the relevant intellectual property from third parties, which licenses may not be available on commercially reasonable terms, if at all. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future drug candidates.

Even if our patent portfolio is unchallenged, it may not provide us with any meaningful protection or prevent competitors or other third parties from designing around our patent claims to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner. For example, a third party may develop a competitive product that provides benefits similar to one or more of our drug candidates but that has a different composition that falls outside the scope of our patent protection. If the patent protection provided by the patents and patent applications we hold or pursue with respect to our drug candidates is not sufficiently broad to impede such competition, our ability to successfully commercialize our drug candidates could be negatively affected, which would harm our business.

If we are unable to protect the confidentiality of our trade secrets our business and competitive position may be harmed.

In addition to the protection afforded by patents, we rely upon unpatented trade secret protection, unpatented know-how and continuing technological innovation to develop and maintain our competitive position. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our collaborators, scientific advisors, employees and consultants, and invention assignment agreements with our consultants and employees. We may not be able to prevent the unauthorized disclosure or use of our technical know-how or other trade secrets by the parties to these agreements, however, despite the existence

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generally of confidentiality agreements and other contractual restrictions. Monitoring unauthorized uses and disclosures is difficult, and we do not know whether the steps we have taken to protect our proprietary technologies will be effective. If any of the collaborators, scientific advisors, employees and consultants who are parties to these agreements breaches or violates the terms of any of these agreements, we may not have adequate remedies for any such breach or violation, and we could lose our trade secrets as a result. We also seek to preserve the integrity and confidentiality of our confidential proprietary information by maintaining physical security on our premises, and physical and electronic security of our information technology systems, but it is possible that these security measures could be breached. Enforcing a claim that a third party illegally obtained and is using our trade secrets, like patent litigation, is expensive and time consuming, and the outcome is unpredictable. In addition, courts outside the United States are sometimes less willing to protect trade secrets.

Our trade secrets could otherwise become known or be independently discovered by our competitors or other third parties. Competitors or other third parties could purchase our drug candidates and attempt to replicate some or all of the competitive advantages we derive from our development efforts, willfully infringe, misappropriate or otherwise violate our intellectual property rights, design around our protected technology or develop their own competitive technologies that fall outside of our intellectual property rights. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If our trade secrets are not adequately protected so as to protect our market against competitors’ products, our competitive position could be adversely affected, as could our business.

Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In addition, periodic maintenance fees, renewal fees, annuity fees and various other government fees on issued patents and patent applications often must be paid to the USPTO and foreign patent agencies over the lifetime of the patent. While an unintentional lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If we fail to maintain the patents and patent applications covering our products or procedures, we may not be able to stop a competitor from marketing products that are the same as or similar to our drug candidates, which would have a material adverse effect on our business.

The intellectual property landscape around our technology is highly dynamic, and third parties may obtain intellectual property rights that could affect our ability to use our technology or otherwise develop and commercialize drug candidates.

Synthetic lethality and the use of inhibitors of specific DNA damage repair pathways in the context of cancer drug development remains a novel approach. Due to the intense research and development that is taking place by several companies, including us and our competitors, in this field, the intellectual property landscape is evolving and in flux, and it may remain uncertain for the coming years. There may be significant intellectual property related litigation and proceedings relating to our owned and in-licensed, and other third party, intellectual property and proprietary rights in the future.

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Our commercial success depends upon our ability to develop, manufacture, market, and sell any drug candidates that we may develop and use our proprietary technologies without infringing, misappropriating, or otherwise violating the intellectual property and proprietary rights of third parties. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our drug candidates may give rise to claims of infringement of the patent rights of others. Moreover, it is not always clear to industry participants, including us, which patents cover various types of therapies, products or their methods of use or manufacture. There may be third-party patents of which we are currently unaware with claims to technologies, methods of manufacture or methods for treatment related to the use or manufacture of our drug candidates. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our drug candidates may infringe. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents. We may be unable to obtain a license to such patents held by third-parties on commercially reasonable terms or at all. In the event that we are unable to obtain licenses to such patents, our ability to develop and commercialize one or more drug candidates may become severely limited. Even if we were able to obtain such a license, it could be granted on non-exclusive terms, thereby providing our competitors and other third parties access to the same technologies licensed to us.

We may initiate or become involved in legal proceedings involving allegations that we are infringing, misappropriating or otherwise violating a third party’s intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

Our commercial success depends in part upon our ability and the ability of our collaborators, to develop, manufacture and sell our drug candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property and other propriety rights of third parties.

The biotechnology and pharmaceutical industries are characterized by extensive and frequent litigation regarding patents and other intellectual property rights. We may in the future become party to, or threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our drug candidates and technology. Our competitors or other third parties may assert infringement, misappropriation or other claims against us, alleging that our products or technologies are covered by their patents or other intellectual property. Given the vast number of patents in our field of technology, we cannot be certain that we do not infringe, misappropriate or otherwise violate existing patents or that we will not infringe, misappropriate or otherwise violate patents that may be granted in the future. If a patent holder believes our product or drug candidate infringes, misappropriates or otherwise violates its patent, the patent holder may sue us even if we have received patent protection for our technology. Moreover, we may face patent infringement claims from non-practicing entities that have no relevant product revenue and against whom our own patent portfolio may thus have no deterrent effect.

If we are found to infringe, misappropriate or otherwise violate a third party’s intellectual property rights, we may be enjoined from further developing or commercializing the infringing, misappropriating or otherwise violating products or technologies. In addition, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, obtain one or more licenses from third parties to continue developing and marketing our drug candidates and technology, pay royalties and/or redesign our infringing products or technologies, which may be impossible or require substantial time and monetary expenditure. In addition, we may choose to obtain one or more licenses from third parties, even in the absence of an action or finding of infringement, misappropriation or other violation. In either case, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain such a license, it could be granted on non-exclusive terms, thereby providing our competitors and other third parties access to the same technologies licensed to us. Without such a license, we could be forced, including by court order, to

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cease developing and commercializing the infringing, misappropriating or otherwise violating technology or drug candidates. A finding of infringement could prevent us from commercializing our drug candidates or force us to cease some of our business operations, which could materially harm our business. If we lose a foreign patent or other intellectual property lawsuit, alleging our infringement, misappropriation or other violation of a competitor’s patents or other intellectual property, we could be prevented from marketing our products in one or more foreign countries, which would have a materially adverse effect on our business. In addition, we may in the future pursue patent challenges with respect to third-party patents, including as a defense against the foregoing infringement, misappropriation or other claims. The outcome of such challenges is unpredictable. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.

We may be subject to damages resulting from claims that we or our employees, consultants or advisors have wrongfully used or disclosed alleged trade secrets of their current or former employers, including our competitors or are in breach of non-competition or non-solicitation agreements with their current or former employers, including our competitors, or claims asserting ownership of what we regard as our own intellectual property.

We could in the future also be subject to claims that we or our employees have inadvertently or otherwise used or disclosed alleged trade secrets or other proprietary information of former employers or competitors. Although we try to ensure that our employees and consultants do not use the intellectual property, proprietary information, know-how or trade secrets of others in their work for us, we may in the future be subject to claims that we caused an employee to breach the terms of his or her non-competition or non-solicitation agreement, or that we or these individuals have, inadvertently or otherwise, used or disclosed the alleged trade secrets or other proprietary information of a former employer, competitor or other third party. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and could be a distraction to our management and employees. If our defenses to these claims fail, in addition to requiring us to pay monetary damages, a court could prohibit us from using technologies or features that are essential to our drug candidates, if such technologies or features are found to incorporate or be derived from the trade secrets or other proprietary information of the former employers. An inability to incorporate such technologies or features would have a material adverse effect on our business, and may prevent us from successfully commercializing our drug candidates. In addition, we may lose valuable intellectual property rights or personnel as a result of such claims. Moreover, any such litigation or the threat thereof may adversely affect our ability to hire employees or contract with independent sales representatives. A loss of key personnel or their work product could hamper or prevent our ability to commercialize our drug candidates, which would have an adverse effect on our business, results of operations and financial condition. Any of the foregoing could harm our business, financial condition, results of operations and prospects.

We may become involved in lawsuits to protect or enforce our patent rights and other intellectual property rights, which could be expensive, time consuming and unsuccessful.

Competitors and other third parties may infringe, misappropriate or otherwise violate our patents, if obtained, and other intellectual property rights. To counter infringement or unauthorized use, we may be required to file infringement, misappropriation or other claims. A court may disagree with our allegations or may refuse to stop the other party from using the technology at issue on the grounds that our or our licensors’ patents do not cover the third-party technology in question. Further, such third parties could counterclaim that we or our licensors’ infringe, misappropriate or otherwise violate their intellectual property or that a patent we have asserted against them is invalid or unenforceable. In patent litigation in the United States, defendant counterclaims challenging the validity, enforceability or scope of asserted patents are commonplace. In

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addition, third parties may initiate legal proceedings against us or our licensors to assert such challenges to our or our licensors’ intellectual property rights. The outcome of any such proceeding is generally unpredictable. To counter or defend against such claims can be expensive and time consuming. An adverse result in any litigation proceeding could put one or more of our or our licensors’ patents at risk of being invalidated or interpreted narrowly. If a defendant were to prevail on a legal assertion of invalidity or unenforceability of our patents covering one of our drug candidates, we would lose at least part, and perhaps all, of the patent protection covering such drug candidate. Competing products may also be sold in other countries in which our patent coverage might neither exist nor be as strong.

Intellectual property litigation could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

Litigation or other legal proceedings relating to intellectual property claims, with or without merit, is unpredictable and generally expensive and time consuming and is likely to divert significant resources from our core business, including distracting our technical and management personnel from their normal responsibilities. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our personnel from their normal responsibilities.

We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon or misappropriating or otherwise violating, or from successfully challenging, our intellectual property rights, or we may be unable to successfully defend ourselves from allegations of infringement, misappropriation or other violation. Uncertainties resulting from the initiation and continuation of patent litigation or other intellectual property proceedings could have a material adverse effect on our ability to compete in the marketplace.

We may not be able to effectively obtain, maintain, protect and enforce our intellectual property and proprietary rights throughout the world.

Filing, prosecuting, maintaining, defending and enforcing patent rights on our drug candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly in developing countries. Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws. Additionally, the patent laws of some foreign countries do not afford intellectual property protection to the same extent as the laws of the United States. Many companies have encountered significant problems in obtaining, maintaining, protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some countries, particularly developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property rights, particularly those relating to biotechnology products. This could make it difficult for us to stop the infringement, misappropriation or other violation of our patent rights or our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the

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patent owner may have limited remedies, which could materially diminish the value of such patent. If we or any of our licensors are forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States. Competitors or other third parties may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection, if our ability to enforce our patent rights to stop infringing, misappropriating or other violating activities is inadequate. These products may compete with our drug candidates, and our patent rights or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Proceedings to enforce our intellectual property and proprietary rights, including our patent rights, in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts and resources from other aspects of our business, put our patent rights at risk of being invalidated or interpreted narrowly, put our owned or in-licensed patents and patent applications at risk of not issuing. Furthermore, while we intend to protect our intellectual property rights in the major markets for our drug candidates, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our drug candidates. Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate to obtain significant commercial advantage from the intellectual property that we develop or license.

We may be subject to claims challenging the inventorship or ownership of any intellectual property, including any patents we may own or in-license in the future.

We may be subject to claims that former employees, collaborators or other third parties have an interest in any patents we may own or in-license in the future, trade secrets, or other intellectual property as an inventor or co-inventor. We may have inventorship disputes arise from conflicting obligations of employees, consultants or others who are involved in developing our drug candidates or other technologies. We generally enter into confidentiality and intellectual property assignment agreements with our employees, consultants, and contractors. These agreements generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property. However, those agreements may not be honored and may not effectively assign intellectual property rights to us. Moreover, there may be some circumstances where we are unable to negotiate for such ownership rights. Disputes regarding ownership or inventorship of intellectual property can also arise in other contexts, such as collaborations and sponsored research. If we are subject to an inventorship, such dispute may lead to litigation which could be expensive and time consuming. If we are unsuccessful, in addition to paying monetary damages, we could lose valuable rights in intellectual property that we regard as our own, such as exclusive ownership of, or right to use, intellectual property that is important to our drug candidates. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.

If we do not obtain patent term extension and data exclusivity for any drug candidates we may develop, our business may be materially harmed.

Depending upon the timing, duration and specifics of any FDA marketing approval of any of our drug candidates, one or more of our U.S. patents, if obtained, may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Action of 1984, or Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended and

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only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended. However, we may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or the term of any such extension is less than we request, our business, financial condition, results of operations and prospects could be materially harmed.

Intellectual property rights do not necessarily address all potential threats.

The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage. For example:

• others may be able to make products that are similar to our drug candidates or utilize similar technology but that are not covered by the claims of any patents that may issue to us, our licensors or our collaborators;

• we or our licensors or collaborators, might not have been the first to make the inventions covered by our owned or licensed pending patent applications, or any patents that may issue in the future;

• we or our licensors or collaborators, might not have been the first to file patent applications covering certain of our or their inventions;

• others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing, misappropriating or otherwise violating our intellectual property rights;

• it is possible that our owned or licensed present or future pending patent applications will not lead to issued patents;

• issued patents that we hold or license rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties, or may not provide us with any competitive advantages;

• our competitors or other third parties might conduct research and development activities in countries where we do not have patent or other intellectual property rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets;

• changes to the patent law and its interpretation in the United States and other jurisdictions could diminish the value of patents in general and may impact the validity, scope or enforceability of our patent rights, thereby impairing our ability to protect our drug candidates;

• we may not develop additional proprietary technologies that are patentable;

• the patents or pending or future patent applications of others, if issued, may harm our business; and

• we may choose not to file a patent application in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.

Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations and prospects.

Changes to the patent law and its interpretation in the United States and in other jurisdictions could diminish the value of patents in general and impact the validity, scope or enforceability of our patent rights, thereby impairing our ability to protect our drug candidates and technologies.

As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining, maintaining, protecting and enforcing patents in the

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biopharmaceutical industry involve both technological and legal complexity and is therefore costly, time consuming and inherently uncertain. Changes in either the patent laws or in their interpretation in any jurisdiction that we seek patent protection diminish our ability to protect our inventions, obtain, maintain and enforce our intellectual property and proprietary rights and, more generally, may affect the value of our intellectual property and proprietary rights. Recent patent reform legislation in the United States and other countries, including the Leahy-Smith America Invents Act, or Leahy-Smith Act, signed into law on September 16, 2011, could increase those uncertainties and costs. The Leahy-Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are prosecuted, redefine prior art and provide more efficient and cost-effective avenues for competitors to challenge the validity of patents. In addition, the Leahy-Smith Act has transformed the U.S. patent system from a “first to invent” system into a “first to file” system. Under a “first-to-file” system, assuming the other requirements for patentability are met, the first inventor to file a patent application generally will be entitled to a patent on the invention regardless of whether another inventor had made the invention earlier.

Moreover, various courts, including the U.S. Supreme Court, has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. Additionally, there have been recent proposals for additional changes to the patent laws of the United States and other countries that, if adopted, could impact our ability to obtain patent protection for our proprietary technology or our ability to enforce rights in our proprietary technology. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on future actions by the U.S. Congress, the U.S. courts, the USPTO and the relevant law-making bodies in other countries, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce any patents that we may obtain in the future which could have a material adverse effect on our existing patent portfolio and our ability to protect and enforce our intellectual property in the future.

If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.

Our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. During trademark registration proceedings, we may receive rejections of our applications by the USPTO or in other foreign jurisdictions. Although we are given an opportunity to respond to such rejections, we may be unable to overcome them. In addition, in the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our trademarks, which may not survive such proceedings. Moreover, any name we have proposed to use with our drug candidate in the United States must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark. Similar requirements exist in Europe. The FDA typically conducts a review of proposed product names, including an evaluation of potential for confusion with other product names. If the FDA or an equivalent administrative body in a foreign jurisdiction objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA. Furthermore, in many countries, owning and maintaining a trademark registration may not provide an adequate defense against a subsequent infringement claim asserted by the owner of a senior trademark.

We may not be able to protect our rights to these trademarks and trade names, which we need to build name recognition among potential partners or customers in our markets of interest. At times, competitors or other third parties may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand

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identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement, misappropriation or other claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade names, domain name or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely affect our business, financial condition, results of operations and prospects.

Risks related to our reliance on third parties

We rely, and expect to continue to rely, on third parties, including independent clinical investigators, CROs, and CDMOs to conduct certain aspects of our clinical trials, preclinical studies, development and regulatory filings. If these third parties do not successfully carry out their contractual duties, comply with applicable regulatory requirements or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our drug candidates and our business could be substantially harmed.

We have relied upon and plan to continue to rely upon third parties, including independent clinical investigators and third-party CROs and CDMOs, as well as potential collaboration partners to conduct certain aspects of our clinical trials, preclinical studies and discovery programs and to monitor and manage data and conduct randomizations and statistical analyses for our ongoing clinical and preclinical programs. We rely on these parties for execution of our clinical trials and preclinical studies, and control only certain aspects of their activities. Nevertheless, we are responsible for ensuring that each of our trials and studies is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards, and our reliance on these third parties does not relieve us of our regulatory responsibilities. We and our third-party contractors, CROs and CDMOs are required to comply with GCP and GMP requirements, which are regulations and guidelines enforced by the FDA and comparable foreign regulatory authorities for all of our drug candidates in clinical development. Regulatory authorities enforce these GCPs and GMPs through periodic inspections of trial sponsors, principal investigators, trial sites and manufacturing facilities. If we or any of these third parties, our CROs or our CDMOs fail to comply with applicable GCPs and GMPs, fail to conduct valid randomizations and statistical analyses, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. Moreover, our business may be adversely affected if any of these third parties violates federal or state fraud and abuse or false claims laws and regulations or healthcare privacy and security laws.

Further, these investigators, CROs and CDMOs are not our employees and we will not be able to control, other than by contract, the amount of resources, including time, which they devote to our drug candidates and clinical trials. These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf. If independent investigators, CROs and CDMOs fail to devote sufficient resources to the development of our drug candidates, if consolidation in the drug manufacturing market results in fewer manufacturers available to us to manufacture the compounds necessary for the development of our drug candidates, or if CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be put on hold by regulatory authorities, extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our drug candidates. As a result, our operations and the commercial prospects for our drug candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed or precluded entirely.

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If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs or to do so on commercially reasonable terms. Switching or adding additional CROs involves additional cost and requires management time and focus. In addition, there is a natural transition period when a new CRO commences work. As a result, delays occur, which can materially impact our ability to meet our desired clinical development timelines. Additionally, CROs may lack the capacity to absorb higher workloads or take on additional capacity to support our needs. Though we carefully manage our relationships with our CROs, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.

We currently rely and expect to rely in the future on the use of manufacturing suites in third-party facilities or third parties to manufacture our drug candidates. Our business could be harmed if we are unable to use third-party manufacturing suites or if the third-party manufacturers fail to provide us with sufficient quantities of our drug candidates or fail to do so at acceptable quality levels or prices.

We do not currently own any facility that may be used as our clinical-scale manufacturing and processing facility and must currently rely on outside vendors to manufacture our drug candidates in clinical quantities, and we expect to rely in the future on these third parties to manufacture our products in sufficient commercial quantities if and when the products are ultimately approved by FDA or other regulatory authorities.

Our reliance on third parties for clinical quantities exposes us to a number of risks, including:

• our third-party manufacturers might be unable to timely manufacture our drug candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any;

• contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately and incompliance with cGMP; and

• our third-party manufacturers could breach or terminate their agreements with us.

Each of these risks could delay or prevent the completion of our clinical trials or the approval of any of our drug candidates by the FDA or result in higher costs. In addition, we will rely on third parties to perform certain specification tests on our drug candidates prior to delivery to patients. If these tests are not appropriately done and test data are not reliable, patients could be put at risk of serious harm and the FDA could place significant restrictions on our company until deficiencies are remedied.

Our third-party manufacturers may also encounter difficulties in production, particularly in scaling up or out to meet commercial demand if and when the products are approved by FDA or other regulatory authorities, validating the production process, and assuring high reliability of the manufacturing process. These problems could include delays or break-downs in logistics and shipping, difficulties with production costs and yields, quality control, product testing, operator error, lack of availability of qualified personnel, or failure to comply with strictly enforced federal, state and foreign regulations.

Our third-party manufacturers are also subject to government inspections and shutdowns by the FDA and other comparable regulatory authorities. If they are unable to reliably produce products to specifications acceptable to the regulatory authorities, we may not obtain or maintain the approvals we need to manufacture our products. Further, our third-party manufacturing facilities may fail to pass government inspections prior to or after the commercial launch of our drug candidates, which would cause significant delays and additional costs required to remediate any deficiencies identified by the regulatory authorities. Any of these challenges could delay approval of our products, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our business, financial condition, results of operations and growth prospects.

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We may be unable to establish any agreements with third-party manufacturers or to do so on acceptable terms. Even if we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including:

• reliance on the third party for regulatory compliance and quality assurance;

• the possible breach of the manufacturing agreement by the third party;

• the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us; and

• reliance on the third party for regulatory compliance, quality assurance, and safety and pharmacovigilance reporting.

Third-party manufacturers may not be able to comply with current good manufacturing practices, or cGMP, regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of drug candidates or medicines, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our medicines and harm our business and results of operations.

Any medicines that we may develop may compete with other drug candidates and products for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us.

Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval. We do not currently have arrangements in place for redundant supply for bulk drug substances. If any one of our current contract manufacturer cannot perform as agreed, we may be required to replace that manufacturer. Although we believe that there are several potential alternative manufacturers who could manufacture our drug candidates, we may incur added costs and delays in identifying and qualifying any such replacement.

Our current and anticipated future dependence upon others for the manufacture of our drug candidates or medicines may adversely affect our future profit margins and our ability to commercialize any medicines that receive marketing approval on a timely and competitive basis.

We anticipate that a portion of the manufacturing of our drug candidates will take place outside the United States through third-party manufacturers. A significant disruption in the operation of those manufacturers, a trade war or political unrest in such countries could materially adversely affect our business, financial condition and results of operations.

We currently contract manufacturing operations to third parties, and it is possible that clinical quantities of our drug candidates will manufactured by third parties outside the United States, including in China. Any disruption in production or inability of such manufacturers outside the United States to produce adequate quantities to meet our needs, whether as a result of a natural disaster or other causes, could impair our ability to operate our business on a day-to-day basis and to continue our development of our drug candidates. Furthermore, since certain of these manufacturers could be located in China, we are exposed to the possibility of product supply disruption and increased costs in the event of changes in the policies of the United States or Chinese governments, political unrest or unstable economic conditions in China. For example, a trade war could lead to tariffs on the chemical intermediates we use that are manufactured in China. Any of these matters could materially and adversely affect our business and results of operations. Any recall of the manufacturing lots or

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similar action regarding our drug candidates used in clinical trials could delay the trials or detract from the integrity of the trial data and its potential use in future regulatory filings. In addition, manufacturing interruptions or failure to comply with regulatory requirements by any of these manufacturers could significantly delay clinical development of potential products and reduce third-party or clinical researcher interest and support of proposed trials. These interruptions or failures could also impede commercialization of our drug candidates and impair our competitive position. Further, we may be exposed to foreign exchange fluctuations. Future appreciation of such local currencies could increase our costs. In addition, our labor costs could continue to rise as wage rates increase due to increased demand for skilled laborers and the availability of skilled labor declines in countries outside the United States.

If our third-party manufacturers use hazardous and biological materials in a manner that causes injury or violates applicable law, we may be liable for damages.

Our research and development activities involve the controlled use of potentially hazardous substances, including chemical and biological materials, by our third-party manufacturers. Our manufacturers are subject to numerous environmental, health and safety laws and regulations, including those governing the use, manufacture, storage, handling and disposal of medical and hazardous materials. Although we believe that our manufacturers’ procedures for using, handling, storing and disposing of these materials comply with legally prescribed standards, we cannot completely eliminate the risk of contamination or injury resulting from medical or hazardous materials. As a result of any such contamination or injury, we may incur liability or local, city, state or federal authorities may curtail the use of these materials and interrupt our business operations. In the event of an accident, we could be held liable for damages or penalized with fines, and the liability could exceed our resources. We do not have any insurance for liabilities arising from medical or hazardous materials. Compliance with applicable environmental laws and regulations is expensive, and current or future environmental regulations may impair our research, development and production efforts, which could harm our business, prospects, financial condition or results of operations.

Our principal investigators, CROs, consultants and employees may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.

We are exposed to the risk that our principal investigators, CROs, consultants and employees may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violate the regulations of the FDA and other regulatory authorities, including those laws requiring the reporting of true, complete and accurate information to such authorities; healthcare fraud and abuse laws and regulations in the United States and abroad; or laws that require the reporting of financial information or data accurately. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Activities subject to these laws also involve the improper use of information obtained in the course of clinical trials or creating fraudulent data in our preclinical studies or clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation. We intend to adopt, prior to the completion of this offering, a code of conduct applicable to all of our employees, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. Additionally, we are subject to the risk that a person could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative

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penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Business disruptions that affect our third-party CROs and manufacturers could seriously harm our future revenue and financial condition and increase our costs and expenses.

While we rely on multiple CROs for preclinical research and development to mitigate potential impacts that may affect any one of our CROs, we have a single CRO for each clinical trial and single contract manufacturers for each step in the manufacturing or our drugs. CROs and other contractors and consultants could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, pandemics and other natural or man-made disasters or business interruptions, for which we are predominantly self-insured. The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses. We rely on third-party manufacturers to produce our drug candidates. Our ability to obtain clinical supplies of our drug candidates could be disrupted if the operations of these suppliers are affected by a man-made or natural disaster or other business interruption.

Risks related to regulatory and other legal compliance matters

Our clinical trials may fail to demonstrate adequately the safety and efficacy of any of our drug candidates, which would delay or prevent further clinical development of those candidates, or prevent marketing approval from FDA or similar regulatory authorities.

We have not received approval to market any of our drug candidates from regulatory authorities in any jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain marketing approvals. To obtain the requisite regulatory approvals to market and sell any of our drug candidates, including CYT-0851, and any other future drug candidates, we must demonstrate through extensive preclinical studies and clinical trials that our products are both safe and effective in humans. To date, we have only a limited amount of safety data and have not generated efficacy data in our ongoing phase 1/2 clinical trial of CYT-0851.

Clinical trials that we conduct may not demonstrate the efficacy and safety necessary to obtain regulatory approval to market our drug candidates. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same drug candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. The current safety experience of CYT-0851 may not be reflective of the ultimate safety profile of the drug, and rare and sometimes fatal side effects may not be seen until much larger numbers of patients have been treated. If the results of our ongoing or future clinical trials are inconclusive with respect to the efficacy of our drug candidates, if we do not meet the clinical endpoints with statistical and clinically meaningful significance, or if there are safety concerns associated with our drug candidates, we may be delayed in obtaining marketing approval, if at all.

Even if the trials are successfully completed, clinical data are often susceptible to varying interpretations and analyses, and we cannot guarantee that the FDA or other comparable foreign regulatory authorities will interpret the results as we do, and more trials could be required before we submit our drug candidates for approval. We cannot guarantee that the FDA or other comparable foreign regulatory authorities will view our drug candidates as having sufficient efficacy to support the indication studied in the clinical trial even if positive

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results are observed in early clinical trials. To the extent that the results of the trials are not satisfactory to the FDA or other comparable foreign regulatory authorities for support of a marketing application, approval of our drug candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our drug candidates. Additionally, any safety or efficacy concerns observed in any of our clinical trials could limit the prospects for regulatory approval of our drug candidates in any disease indication or result in future limitations after approval, which could have a material adverse effect on our business, financial condition and results of operations.

Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

If we experience delays in obtaining approval or if we fail to obtain approval of our drug candidates, the commercial prospects for our drug candidates may be harmed and our ability to generate revenues will be impaired.

Our relationships with healthcare providers, physicians, and third-party payors will be subject to applicable anti-kickback, fraud and abuse, anti-bribery, physician payment transparency and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, and diminished profits and future earnings.

Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research, market, sell, and distribute our medicines for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:

• federal Anti-Kickback Statute, which prohibits, among other things, persons from offering, soliciting, receiving or providing remuneration, directly or indirectly, to induce either the referral of an individual, or the purchasing or ordering of, a good or service for which payment may be made under federal healthcare programs such as Medicare and Medicaid;

• federal false claims, false statements and civil monetary penalties laws prohibiting, among other things, any person from knowingly presenting, or causing to be presented, a false claim for payment of government funds or knowingly making, or causing to be made, a false statement material to a false claim;

• the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which, in addition to privacy protections applicable to healthcare providers and other entities, prohibits executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;

• the Physician Payments Sunshine Act, which requires pharmaceutical and medical device companies to report information related to certain payments and transfers of value to certain healthcare providers to the Center for Medicare & Medicaid Services, as well as ownership and investment interests held by physicians and their immediate family members; and

• analogous state and foreign laws and regulations, such as state anti-kickback, anti-bribery and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers, as well as other state laws that require companies to comply with specific

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compliance standards, restrict financial interactions between companies and healthcare providers and require companies to report information related to payments to health care providers or marketing expenditures.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. Given the breadth of the laws and regulations, limited guidance for certain laws and regulations and evolving government interpretations of the laws and regulations, governmental authorities may possibly conclude that our business practices may not comply with healthcare laws and regulations, including, without limitation, certain of our advisory board agreements with physicians who receive stock or stock options as compensation for services provided to us. If our operations are found to be in violation of any of the laws described above or any other government regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from participation in government health care programs, such as Medicare and Medicaid, imprisonment, and the curtailment or restructuring of our operations, any of which could adversely affect our business, financial condition, results of operations, and prospects.

Healthcare legislative reform measures may have a material adverse effect on our business and results of operations.

The U.S. and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system that could prevent or delay marketing approval or reimbursement of our current or future drug candidates or any future drug candidates, restrict or regulate post-approval activities and affect our ability to profitably sell a product for which we obtain marketing approval. In particular, in the U.S., there have been and continue to be a number of legislative initiatives at the federal and state level to contain healthcare costs. For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, of collectively, the ACA, was enacted, which substantially changed the way healthcare is financed by both government and private payors. Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. It is unclear how any efforts to challenge, repeal, or replace the ACA will impact the ACA or our business.

Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements, (ii) additions or modifications to product labeling, (iii) the recall or discontinuation of our products or (iv) additional record-keeping requirements. Further, healthcare reform may result in changes to payment methodologies, the implementation of pharmaceutical and biological product price controls, and reductions in Medicare and other healthcare funding. If any such changes were to be imposed, they could adversely affect the operation of our business.

The successful commercialization of our drug candidates will depend in part on the extent to which third-party payors establish coverage, adequate reimbursement levels and pricing policies.

Our ability to obtain coverage and adequate reimbursement for our drug candidates by governmental healthcare programs, private health insurers, and other third-party payors will have an effect on our ability to successfully commercialize our drug candidates. We cannot be sure that coverage and reimbursement will be available for our drug candidates or any product that we may develop, and any reimbursement that may become available may not be adequate or may be decreased or eliminated in the future. No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States. Therefore, coverage and reimbursement for products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and

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clinical support for the use of our drug candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. If reimbursement is not available, is delayed, or is available only at limited levels, we may not be able to successfully commercialize our drug candidates, and may not be able to obtain a satisfactory financial return on our drug candidates.

We, our collaborators and our service providers are subject to a variety of U.S. and international restrictive data privacy and security laws, regulations, contractual obligations and industry standards governing the use, processing and cross-border transfer of data and personal information, which could increase compliance costs and our failure to comply with them could subject us to potentially significant liability, fines or penalties and otherwise harm our business.

We maintain a large quantity of sensitive information, including confidential business information, protected health information and other personal information, and are subject to laws and regulations governing the privacy and security of such information. The global data protection landscape is rapidly evolving, and we and our collaborators and service providers may be affected by or subject to new, amended or existing laws and regulations in the future, including as our operations continue to expand or if we operate in foreign jurisdictions. These laws and regulations may be subject to differing interpretations, which adds to the complexity of processing personal data. Guidance on implementation and compliance practices are often updated or otherwise revised.

In particular, the conduct of our clinical trials may be subject to privacy restrictions based on U.S. and non-U.S. regulations. In many jurisdictions, enforcement actions and consequences for noncompliance are rising. In the United States, these include enforcement actions in response to rules and regulations promulgated under the authority of federal agencies and state attorneys general and legislatures and consumer protection agencies. Laws in all 50 states require businesses to provide notice to customers whose personally identifiable information has been disclosed as a result of a data breach. The laws are not consistent, and compliance in the event of a widespread data breach is costly. States are also constantly amending existing laws, requiring attention to frequently changing regulatory requirements. For example, we may be subject to the California Consumer Privacy Act, or the CCPA, which became effective on January 1, 2020, and was further amended by the California Privacy Rights Act, or the CPRA, on November 3, 2020. As currently written, the CCPA may impact our business activities and exemplifies the vulnerability of our business to the evolving regulatory environment related to personal data and protected health information. Among other things, the CCPA requires covered companies to provide new disclosures to California residents and provide such residents new data protection and privacy rights, including the ability to opt-out of certain sales of personal information. The CPRA significantly modifies the CCPA by expanding residents’ rights with respect to certain personal information and creates a new state agency to oversee implementation and enforcement efforts. Many of the CPRA’s provisions will become effective on January 1, 2023. The CCPA provides for civil penalties for violations, as well as a private right of action for certain data breaches. This private right of action may increase the likelihood of, and risks associated with, data breach litigation, including class action litigation.

Additionally, the collection, use, storage, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the EU General Data Protection Regulation, or the GDPR. The GDPR, which came into effect on May 25, 2018, introduced new data protection requirements in the European Union, as well as potential fines for noncompliant companies of up to the greater of €20 million or 4% of annual global revenue. The regulation imposes numerous new requirements for the collection, use and disclosure of personal information, including more stringent requirements relating to consent and the information that must be shared with data subjects about how their personal information is used, the obligation to notify regulators and affected individuals of personal data breaches, extensive new internal privacy governance obligations and obligations to honor expanded rights of individuals in relation to their personal information (e.g., the right to access, correct and delete their data). Among other requirements, the GDPR

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regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of current transfer mechanisms between the EU and the United States remains uncertain. For example, in 2016, the EU and United States agreed to a transfer framework for data transferred from the EU to the United States, called the Privacy Shield, but the Privacy Shield was invalidated in July 2020 by the Court of Justice of the European Union. At this time, we do not believe we are subject to the GDPR, but should this change, the GDPR will increase our responsibility and potential liability in relation to personal data that we process, and we may be required to put in place additional mechanisms to ensure compliance with the new EU data protection rules. Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities. Further, in June 2016, the UK held a referendum and voted in favor of leaving the EU and, on January 31, 2020, the UK exited the EU and the implementation period or transition period ended on December 31, 2020. This referendum and exit has created political and economic uncertainty, particularly in the UK and the EU, and this uncertainty may last for years. Further, following the withdrawal of the United Kingdom from the EU and the European Economic Area, or the EEA, on January 31, 2020 and the end of the transition period, we will have to comply with the GDPR and separately the GDPR as implemented in the United Kingdom, each regime having the ability to fine up to the greater of €20 million/£17 million or 4% of global turnover. The relationship between the United Kingdom and the EU and the EEA in relation to certain aspects of data protection law remains unclear, including how data transfers between EU and EEA member states and the United Kingdom will be treated. Our business could be affected during this period of uncertainty, and perhaps longer, by the impact of the UK’s referendum and exit.

Compliance with U.S. and international data protection laws and regulations could require us to take on more onerous obligations in our contracts, restrict our ability to collect, use and disclose data, or in some cases, impact our ability to operate in certain jurisdictions. Failure to comply with U.S. and international data protection laws and regulations could result in government enforcement actions (which could include civil or criminal penalties), private litigation or adverse publicity and could negatively affect our operating results and business. Moreover, clinical trial subjects about whom we or our potential collaborators obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information. Claims that we have violated individuals’ privacy rights, failed to comply with data protection laws, or breached our contractual obligations, even if we are not found liable, could be expensive and time consuming to defend and could result in adverse publicity that could harm our business.

We may face potential liability if we obtain identifiable patient health information from clinical trials sponsored by us.

Most healthcare providers, including certain research institutions from which we may obtain patient health information, are subject to privacy and security regulations promulgated under HIPAA, as amended by the HITECH. We are not currently classified as a covered entity or business associate under HIPAA and thus are not directly subject to its requirements or penalties. However, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, in the future, we may maintain sensitive personally identifiable information, including health information, that we receive throughout the clinical trial process, in the course of our research collaborations, and directly from individuals (or their healthcare providers) who may enroll in patient assistance programs if we choose to implement such programs. As such, we may be subject to state laws requiring notification of

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affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR includes restrictions on cross-border data transfers. The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries. Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities. Further, the United Kingdom’s decision to leave the European Union, referred to as Brexit, has created uncertainty with regard to data protection regulation in the United Kingdom. In particular, it is unclear how data transfers to and from the United Kingdom will be regulated now that the United Kingdom has left the European Union.

Furthermore, certain health privacy laws, data breach notification laws, consumer protection laws and genetic testing laws may apply directly to our operations and/or those of our collaborators and may impose restrictions on our collection, use and dissemination of individuals’ health information. Patients about whom we or our collaborators may obtain health information, as well as the providers who may share this information with us, may have statutory or contractual rights that limit our ability to use and disclose the information. We may be required to expend significant capital and other resources to ensure ongoing compliance with applicable privacy and data security laws. Claims that we have violated individuals’ privacy rights or breached our contractual obligations, even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

If we or third-party CMOs, CROs or other contractors or consultants fail to comply with applicable federal, state/provincial or local regulatory requirements, we could be subject to a range of regulatory actions that could affect our or our contractors’ ability to develop and commercialize our therapeutic candidates and could harm or prevent sales of any affected therapeutics that we are able to commercialize, or could substantially increase the costs and expenses of developing, commercializing and marketing our therapeutics. Any threatened or actual government enforcement action could also generate adverse publicity and require that we devote substantial resources that could otherwise be used in other aspects of our business. Increasing use of social media could give rise to liability, breaches of data security or reputational damage.

Even if we receive regulatory approval of any drug candidates, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense, and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our drug candidates.

If any of our drug candidates are approved, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies and submission of safety, efficacy and other post-market information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities. In addition, we will be subject to continued compliance with cGMP and GCP requirements for any clinical trials that we conduct post-approval.

Manufacturers and manufacturers’ facilities are required to comply with extensive FDA and comparable foreign regulatory authority requirements, including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our contract manufacturers will be subject to continual review

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and inspections to assess compliance with cGMP and adherence to commitments made in any NDA, other marketing application, and previous responses to inspection observations. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production and quality control.

Any regulatory approvals that we receive for our drug candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including phase 4 clinical trials and surveillance to monitor the safety and efficacy of the drug candidate. The FDA may also require a REMS program as a condition of approval of our drug candidates, which could entail requirements for long-term patient follow-up, a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Comparable foreign regulatory authorities may also have programs similar to REMS. In addition, if the FDA or a comparable foreign regulatory authority approves our drug candidates, we will have to comply with requirements including submissions of safety and other post-marketing information and reports and registration.

The FDA may impose consent decrees or withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with our drug candidates, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

• restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls;

• fines, warning letters or holds on clinical trials;

• refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals;

• product seizure or detention or refusal to permit the import or export of our drug candidates; and

• injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the market. Products may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses and a company that is found to have improperly promoted off-label uses may be subject to significant liability. However, physicians may, in their independent medical judgment, prescribe legally available products for off-label uses. The FDA does not regulate the behavior of physicians in their choice of treatments but the FDA does restrict manufacturer’s communications on the subject of off-label use of their products. The policies of the FDA and of comparable foreign regulatory authorities may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our drug candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability.

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Risks related to this offering and ownership of our common stock

We do not know whether a market will develop for our common stock or what the market price of our common stock will be, and, as a result, it may be difficult for you to sell your shares of our common stock.

Before this offering, there was no public trading market for our common stock. If a market for our common stock does not develop or is not sustained, it may be difficult for you to sell your shares of common stock at an attractive price or at all. We cannot predict the prices at which our common stock will trade. It is possible that in one or more future periods our results of operations may be below the expectations of public market analysts and investors, and, as a result of these and other factors, the price of our common stock may fall.

You will incur immediate and substantial dilution as a result of this offering.

If you purchase common stock in this offering, you will incur immediate and substantial dilution of $                per share, representing the difference between the assumed initial public offering price of $                per share, the midpoint of the price range set forth on the cover page of this prospectus, and our pro forma net tangible book value per share after giving effect to this offering and the automatic conversion of all outstanding shares of our preferred stock upon the closing of this offering. Moreover, we issued options in the past that allow the holders to acquire common stock at prices significantly below the assumed initial public offering price. As of February 28, 2021, there were 8,453,312 shares subject to outstanding options with a weighted-average exercise price of $1.20 per share. To the extent that these outstanding options are ultimately exercised or the underwriters exercise their option to purchase additional shares, you will incur further dilution. In addition, any future issuances of our common stock in securities offerings following this offering will result in further dilution. For a further description of the dilution you will experience immediately after this offering, see “Dilution.”

If securities analysts do not publish research or reports about our business or if they publish negative evaluations of our stock, the price of our stock could decline.

The trading market for our common stock will rely in part on the research and reports that industry or financial analysts publish about us or our business. We do not currently have and may never obtain research coverage by industry or financial analysts. If no or few analysts commence coverage of us, the trading price of our stock would likely decrease. Even if we do obtain analyst coverage, if one or more of the analysts covering our business downgrade their evaluations of our stock, the price of our stock could decline. If one or more of these analysts cease to cover our stock, we could lose visibility in the market for our stock, which in turn could cause our stock price to decline.

A variety of risks associated with operating internationally could materially adversely affect our business or that of our collaborators.

Our business strategy includes potentially expanding internationally if any of our drug candidates receives regulatory approval. Doing business internationally involves several risks, including, but not limited to:

• multiple, conflicting, and changing laws and regulations, such as privacy regulations, tax laws, export and import restrictions, economic sanctions laws and regulations, employment laws, regulatory requirements, and other governmental approvals, permits, and licenses;

• failure by us to obtain and maintain regulatory approvals for the use of our products in various countries;

• additional potentially relevant third-party patent rights;

• complexities and difficulties in obtaining protection and enforcing our intellectual property;

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• difficulties in staffing and managing foreign operations;

• complexities associated with managing multiple payor reimbursement regimes, government payors, or patient self-pay systems;

• limits in our ability to penetrate international markets;

• financial risks, such as longer payment cycles, difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and payment for our products, and exposure to foreign currency exchange rate fluctuations;

• natural disasters, political and economic instability, including wars, terrorism and political unrest, outbreak of disease, boycotts, curtailment of trade, and other business restrictions;

• certain expenses, including, among others, expenses for travel, translation, and insurance; and

• regulatory and compliance risks that relate to maintaining accurate information and control over sales and activities that may fall within the purview of the U.S. Foreign Corrupt Practices Act of 1977, as amended, or the FCPA, its books and records provisions, or its anti-bribery provisions, as well as other applicable laws and regulations prohibiting bribery and corruption.

Any of these factors could significantly harm any future international expansion and operations and, consequently, our results of operations.

A significant portion of our total outstanding shares is restricted from immediate resale but may be sold into the market in the near future, which could cause the market price of our common stock to decline significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares of common stock intend to sell shares, could reduce the market price of our common stock. After this offering and after giving effect to the conversion of all outstanding shares of our preferred stock into shares of our common stock upon the closing of this offering, we will have                 shares of common stock outstanding, or                 shares if the underwriters exercise their option to purchase additional shares in full, in each case based on the shares of our common stock outstanding as of February 28, 2021. Of these shares, the shares (or shares if the underwriters exercise their option to purchase additional shares in full) we are selling in this offering may be resold in the public market immediately, unless purchased by our affiliates. The remaining shares are currently restricted under securities laws or as a result of lock-up or other agreements, but will be able to be sold after this offering as described in the “Shares Eligible for Future Sale” section of this prospectus. Moreover, after this offering, holders of an aggregate of shares of our common stock will have rights, subject to conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders. We also plan to register all shares of common stock that we may issue under our equity compensation plans or that are issuable upon exercise of outstanding options. Once we register these shares, they can be freely sold in the public market upon issuance and once vested, subject to volume limitations applicable to affiliates and the lock-up agreements described in the “Underwriting” section of this prospectus. If any of these additional shares are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline.

Insiders will continue to have substantial influence over us after this offering, which could limit your ability to affect the outcome of key transactions, including a change of control.

After this offering, our directors and executive officers and their affiliates will beneficially own shares representing approximately        % of our outstanding common stock. As a result, these stockholders, if they act

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together, will be able to influence our management and affairs and all matters requiring stockholder approval, including the election of directors and approval of significant corporate transactions. This concentration of ownership may have the effect of delaying or preventing a change in control of our company and might affect the market price of our common stock.

We do not expect to pay any dividends for the foreseeable future. Investors in this offering may never obtain a return on their investment.

You should not rely on an investment in our common stock to provide dividend income. We do not anticipate that we will pay any dividends to holders of our common stock in the foreseeable future. Instead, we plan to retain any earnings to maintain and expand our existing operations. In addition, any future credit facility may contain terms prohibiting or limiting the amount of dividends that may be declared or paid on our common stock. Accordingly, investors must rely on sales of their common stock after price appreciation, which may never occur, as the only way to realize any return on their investment. As a result, investors seeking cash dividends should not purchase our common stock.

We have broad discretion in the use of the net proceeds from this offering and may not use them effectively.

We cannot specify with certainty the particular uses of the net proceeds we will receive from this offering. Our management will have broad discretion in the application of the net proceeds, including for any of the purposes described in “Use of Proceeds.” Accordingly, you will have to rely upon the judgment of our management with respect to the use of the proceeds, with only limited information concerning management’s specific intentions. Our management may spend a portion or all of the net proceeds from this offering in ways that our stockholders may not desire or that may not yield a favorable return. The failure by our management to apply these funds effectively could harm our business, financial condition, results of operations and prospects. Pending their use, we may invest the net proceeds from this offering in a manner that does not produce income or that loses value.

We are an “emerging growth company” and a “smaller reporting company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common stock less attractive to investors.

We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and may remain an emerging growth company for up to five years. For so long as we remain an emerging growth company, we are permitted and plan to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include not being required to comply with the auditor attestation requirements of SOX Section 404, not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, reduced disclosure obligations regarding executive compensation, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved. As a result, the information we provide stockholders will be different than the information that is available with respect to other public companies. In this prospectus, we have not included all of the executive compensation related information that would be required if we were not an emerging growth company and we have provided only two years of audited financial statements and only two years of related “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock, and our stock price may be more volatile.

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In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.

Further, even after we no longer qualify as an emerging growth company, we may still qualify as a “smaller reporting company,” which would allow us to take advantage of many of the same exemptions from disclosure requirements, including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements. In addition, if we are a smaller reporting company, we would not be required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, or Section 404. These exemptions and reduced disclosures in our SEC filings due to our status as a smaller reporting company may make it harder for investors to analyze our results of operations and financial prospects. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock prices may be more volatile.

Provisions in our amended and restated certificate of incorporation, our amended and restated by-laws and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders, and may prevent attempts by our stockholders to replace or remove our current management.

Our amended and restated certificate of incorporation, amended and restated by-laws and Delaware law contain provisions that may have the effect of discouraging, delaying or preventing a change in control of us or changes in our management that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. Our amended and restated certificate of incorporation and by-laws, which will become effective upon the closing of this offering, include provisions that:

• authorize “blank check” preferred stock, which could be issued by our board of directors without stockholder approval and may contain voting, liquidation, dividend and other rights superior to our common stock;

• create a classified board of directors whose members serve staggered three-year terms;

• specify that special meetings of our stockholders can be called only by our board of directors;

• prohibit stockholder action by written consent;

• establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors;

• provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum;

• provide that our directors may be removed for cause only;

• specify that no stockholder is permitted to cumulate votes at any election of directors;

• expressly authorized our board of directors to modify, alter or repeal our amended and restated by-laws; and

• require supermajority votes of the holders of our common stock to amend specified provisions of our amended and restated certificate of incorporation and amended and restated by-laws.

These provisions, alone or together, could delay or prevent hostile takeovers and changes in control or changes in our management. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock.

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In addition, because we are incorporated in the State of Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of Delaware, or the DGCL, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

Any provision of our amended and restated certificate of incorporation, amended and restated by-laws or Delaware law that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.

Our amended and restated certificate of incorporation designates the state or federal courts within the State of Delaware as the exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our amended and restated certificate of incorporation provides that, subject to limited exceptions, the state or federal courts within the State of Delaware will be exclusive forums for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or other employees to us or our stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the DGCL, our amended and restated certificate of incorporation or our amended and restated by-laws, (4) any action to interpret, apply, enforce or determine the validity of our amended and restated certificate of incorporation or our amended and restated bylaws or (5) any other action asserting a claim against us that is governed by the internal affairs doctrine; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act or to any claim for which the federal courts have exclusive jurisdiction. Our amended and restated certificate of incorporation also provides that, unless we consent in writing to the selection of an alternative forum, the U.S. federal district courts shall be the exclusive forum for the resolution of any claims arising under the Securities Act. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our amended and restated certificate of incorporation described above. This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and employees.

Alternatively, if a court were to find these provisions of our amended and restated certificate of incorporation inapplicable to, or unenforceable in respect of, one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could adversely affect our business and financial condition.

The market price of our common stock may be volatile, which could result in substantial losses for investors purchasing shares in this offering.

The initial public offering price for our common stock was determined through negotiations with the underwriters. This initial public offering price may vary from the market price of our common stock after the offering. As a result, you may not be able to sell your common stock at or above the initial public offering price. Some of the factors that may cause the market price of our common stock to fluctuate include:

• the success of existing or new competitive drug candidates or technologies;

• the timing and results of clinical trials and preclinical studies for any drug candidates that we may develop;

• failure or discontinuation of any of our product development and research programs;

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• results of preclinical studies, clinical trials, or regulatory approvals of drug candidates of our competitors, or announcements about new research programs or drug candidates of our competitors;

• developments or changing views regarding synthetic lethality or the use of PARP inhibition in the context of cancer drug development;

• commencement or termination of collaborations for our product development and research programs;

• regulatory or legal developments in the United States and other countries;

• developments or disputes concerning patent applications, issued patents, or other proprietary rights;

• the recruitment or departure of key personnel;

• the level of expenses related to any of our research programs, clinical development programs, or drug candidates that we may develop;

• the results of our efforts to develop additional drug candidates or products;

• actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts;

• announcement or expectation of additional financing efforts;

• sales of our common stock by us, our insiders or other stockholders;

• expiration of market stand-off or lock-up agreement;

• variations in our financial results or those of companies that are perceived to be similar to us;

• changes in estimates or recommendations by securities analysts, if any, that cover our stock;

• changes in the structure of healthcare payment systems;

• market conditions in the pharmaceutical and biotechnology sectors;

• general economic, industry, and market conditions; and

• the other factors described in this “Risk Factors” section.

In recent years, the stock market in general, and the market for pharmaceutical and biotechnology companies in particular, has experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to changes in the operating performance of the companies whose stock is experiencing those price and volume fluctuations. Broad market and industry factors may seriously affect the market price of our common stock, regardless of our actual operating performance. These fluctuations may be even more pronounced in the trading market for our stock shortly following this offering. Following periods of such volatility in the market price of a company’s securities, securities class action litigation has often been brought against that company. Because of the potential volatility of our stock price, we may become the target of securities litigation in the future.

We will incur increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new compliance initiatives and corporate governance practices.

As a public company, and particularly after we are no longer an “emerging growth company,” we will incur significant legal, accounting, and other expenses that we did not incur as a private company. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of

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the Nasdaq Global Market, and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. We expect that we will need to hire additional accounting, finance, and other personnel in connection with our becoming, and our efforts to comply with the requirements of being, a public company, and our management and other personnel will need to devote a substantial amount of time towards maintaining compliance with these requirements. These requirements will increase our legal and financial compliance costs and will make some activities more time-consuming and costly. For example, we expect that the rules and regulations applicable to us as a public company may make it more difficult and more expensive for us to obtain director and officer liability insurance, which could make it more difficult for us to attract and retain qualified members of our board of directors. We are currently evaluating these rules and regulations and cannot predict or estimate the amount of additional costs we may incur or the timing of such costs. These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Pursuant to SOX Section 404, we will be required to furnish a report by our management on our internal control over financial reporting beginning with our second filing of an Annual Report on Form 10-K with the SEC after we become a public company. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with SOX Section 404 within the prescribed period, we will be engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, potentially engage outside consultants, adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented, and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by SOX Section 404. If we identify one or more material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

Risks related to general legal matters

Potential product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any products that we may develop.

The use of any medicine drug candidates we may develop in clinical trials and the sale of any products for which we obtain marketing approval exposes us to the risk of product liability claims. Product liability claims might be brought against us by patients, healthcare providers, pharmaceutical companies or others selling or otherwise coming into contact with our products. On occasion, large judgments have been awarded in class action lawsuits based on drugs that had unanticipated adverse effects. If we cannot successfully defend against product liability claims, we could incur substantial liability and costs. In addition, regardless of merit or eventual outcome, product liability claims may result in:

• impairment of our business reputation and significant negative media attention;

• withdrawal of participants from our clinical trials;

• significant costs to defend the litigation;

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• distraction of management’s attention from our primary business;

• substantial monetary awards to patients or other claimants;

• inability to commercialize a drug candidate;

• product recalls, withdrawals or labeling, marketing or promotional restrictions;

• decreased market demand for any product; and

• loss of revenue.

The product liability insurance we currently carry, and any additional product liability insurance coverage we acquire in the future, may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive and, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. If we obtain marketing approval for any drug candidate, we intend to acquire insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. A successful product liability claim, or series of claims, brought against us could cause our share price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operation and business, including preventing or limiting the commercialization of any precision medicine drug candidates we develop.

U.S. federal income tax reform could adversely affect our business and financial condition.

The rules dealing with U.S. federal, state, and local income taxation are constantly under review by persons involved in the legislative process and by the Internal Revenue Service and the U.S. Treasury Department. Changes to tax laws (which changes may have retroactive application) could adversely affect us or holders of our common stock. In recent years, many such changes have been made and changes are likely to continue to occur in the future. For example, on March 27, 2020, the United States enacted the CARES Act, which included certain changes in tax law intended to stimulate the U.S. economy in light of the COVID-19 coronavirus outbreak, including temporary beneficial changes to the treatment of net operating losses, interest deductibility limitations and payroll tax matters. Additionally, on December 22, 2017, the United States enacted the Tax Cuts and Jobs Act, or the TCJA, which significantly reformed the Internal Revenue Code of 1986, as amended, or the Code. The TCJA included significant changes to corporate and individual taxation, some of which could adversely impact an investment in our common stock. Many of the provisions of the TCJA and CARES Act still require guidance through the issuance or finalization of regulations by the U.S. Treasury Department in order to fully assess their effects, and there many be substantial delays before such regulations are promulgated or finalized, increasing the uncertainty as to the ultimate effects of the TCJA and CARES Act on us and our stockholders. There also may be technical corrections legislation or other legislative changes proposed with respect to the TCJA and CARES Act, the effects of which cannot be predicted and may be adverse to us or our stockholders. Future changes in tax laws could have a material adverse effect on our business, cash flow, financial condition or results of operations. We urge investors to consult with their legal and tax advisers regarding the implications of potential changes in tax laws on an investment in our common stock.

We are subject to U.S. and certain foreign export and import controls, sanctions, embargoes, anti-corruption laws, and anti-money laundering laws and regulations. Compliance with these legal standards could impair our ability to compete in domestic and international markets. We can face criminal liability and other serious consequences for violations, which can harm our business.

We are subject to export control and import laws and regulations, including the U.S. Export Administration Regulations, U.S. Customs regulations, various economic and trade sanctions regulations administered by the

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U.S. Treasury Department’s Office of Foreign Assets Controls, the U.S. Foreign Corrupt Practices Act of 1977, as amended, or FCPA, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, the USA PATRIOT Act, and other state and national anti-bribery and anti-money laundering laws in the countries in which we conduct activities. Anti-corruption laws are interpreted broadly and prohibit companies and their employees, agents, contractors, and other collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector. We may engage third parties for clinical trials outside of the United States, to sell our products abroad once we enter a commercialization phase, and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals. We may also have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations. We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors, and other collaborators, even if we do not explicitly authorize or have actual knowledge of such activities. Any violations of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequences.

We could be subject to securities class action litigation.

In the past, securities class action litigation has often been brought against companies following a decline in the market price of their securities. This risk is especially relevant for us because biotechnology and pharmaceutical companies have experienced significant share price volatility in recent years. Because of the potential volatility of our stock price, we may become the target of securities litigation in the future. Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.

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Special note regarding forward-looking statements

This prospectus contains forward-looking statements that are based on management’s beliefs and assumptions and on information currently available to management. All statements other than statements of historical facts contained in this prospectus are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning:

• the initiation, timing, progress and results of our current and future preclinical studies and clinical trials and related preparatory work and the period during which the results of the trials will become available, as well as our research and development programs;

• our estimates regarding expenses, future revenue, capital requirements and needs for additional financing;

• our ability to obtain regulatory approval of CYT-0851, CYT-1853 and any of our current and future drug candidates that we develop;

• our ability to identify and develop additional drug candidates;

• business disruptions affecting the initiation, patient enrollment, development and operation of our clinical trials, including a public health emergency, such as the recent COVID-19 pandemic;

• our expectations regarding the potential market size and the rate and degree of market acceptance for any drug candidates that we develop;

• the effects of competition with respect to CYT-0851, CYT-1853 or any of our other current or future drug candidates, as well as innovations by current and future competitors in our industry;

• our ability to fund our working capital requirements;

• our intellectual property position, including the scope of protection we are able to establish, maintain, defend and enforce for intellectual property rights covering our drug candidates;

• our financial performance and our ability to effectively manage our anticipated growth;

• our ability to obtain additional funding for our operations and our expected use of proceeds from this offering; and

• other risks and uncertainties, including those listed under the section titled “Risk Factors.”

The forward-looking statements in this prospectus are only predictions and are based largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this prospectus and are subject to a number of known and unknown risks, uncertainties and assumptions, including those described under the sections in this prospectus entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this prospectus. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. Moreover, we operate in an evolving environment. New risks and uncertainties may emerge from time to time, and it is not possible for management to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

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Use of proceeds

We estimate that the net proceeds to us from the sale of the shares of common stock in this offering will be approximately $         million, or approximately $         million if the underwriters exercise their option to purchase additional shares in full, based upon an assumed initial price to the public of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

Each $1.00 increase (decrease) in the assumed initial public offering price of $         per share would increase (decrease) the net proceeds to us from this offering by approximately $        , assuming the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same. We may also increase or decrease the number of shares we are offering. Each increase (decrease) of 1,000,000 shares in the number of shares offered by us would increase (decrease) the net proceeds to us from this offering by approximately $        , assuming that the assumed initial public offering price remains the same, and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

We currently expect to use the net proceeds from this offering, together with our existing cash and cash equivalents, as follows:

• approximately $         million to advance the clinical development of CYT-0851;

• approximately $         million to advance the development of CYT-1853;

• approximately $         million for other research and development activities; and

• the remainder, if any, for working capital and other general corporate purposes.

Based on our planned use of the net proceeds from this offering and our existing cash and cash equivalents, we estimate that such funds will be sufficient to fund our operating expenses and capital expenditure requirements into             . We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we expect.

We may also use a portion of the net proceeds from this offering to acquire, in-license or invest in products, technologies or businesses that are complementary to our business. The amounts and timing of our actual expenditures will depend on numerous factors, including the progress of our clinical and preclinical development efforts, our operating costs and other factors described under “Risk Factors” in this prospectus.

Our expected use of net proceeds from this offering represents our current intentions based upon our present plans and business condition. As of the date of this prospectus, we cannot predict with complete certainty all of the particular uses for the net proceeds to be received upon the completion of this offering or the actual amounts that we will spend on the uses set forth above.

We may find it necessary or advisable to use the net proceeds for other purposes, and we will have broad discretion in the application of the net proceeds. Pending the uses described above, we plan to invest the net proceeds from this offering in short-term, interest-bearing obligations, investment-grade instruments, certificates of deposit or direct or guaranteed obligations of the U.S. government.

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Dividend policy

We have never declared or paid any cash dividends on our capital stock. We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends in the foreseeable future. Any future determination related to our dividend policy will be made at the discretion of our board of directors after considering our financial condition, results of operations, capital requirements, business prospects and other factors our board of directors deems relevant, and subject to the restrictions contained in our current and any future financing instruments. Our ability to pay cash dividends on our capital stock in the future may also be limited by the terms of any preferred securities we may issue or agreements governing any indebtedness we may incur.

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Capitalization

The following table summarizes our cash and cash equivalents and capitalization as of December 31, 2020:

• on an actual basis;

• on a pro forma basis to give effect to (i) our issuance and sale in February 2021 of 21,784,885 shares of Series C redeemable convertible preferred stock for gross proceeds of $80.0 million, and (ii) the automatic conversion of all outstanding shares of our redeemable convertible preferred stock into an aggregate of 82,802,881 shares of common stock upon the closing of this offering; and

• on a pro forma as adjusted basis to give further effect to (i) our issuance and sale of                  shares of our common stock in this offering at an assumed initial public offering price of $             per share, which is the midpoint of the price range set forth on the cover page of this prospectus, after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us, and (ii) the filing and effectiveness of our amended and restated articles of incorporation.

You should read the information in this table together with the consolidated financial statements and related notes to those statements, as well as the information set forth under the headings “Selected Financial Data” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.”

	December 31, 2020
	Actual			Pro forma			Pro forma as adjusted
	(in thousands, except share and per share data)
Cash and cash equivalents	$	10,938		$	90,877		$
Redeemable convertible preferred stock (Series A, and Series B), $0.001 par value; 77,017,995 shares authorized, 61,017,996 shares issued and outstanding, actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted	$	57,411		$	—
Stockholders’ (deficit) equity
Preferred stock,              par value; no shares authorized, issued or outstanding, actual;              shares authorized and no shares issued or outstanding, pro forma and pro forma as adjusted
Common stock, $0.001 par value; 100,000,000 shares authorized, 9,269,749 shares issued and 6,968,483 shares outstanding, actual;              shares authorized, 92,072,630 shares issued and 89,771,364 shares outstanding, pro forma;              shares authorized,              shares issued and              shares outstanding, pro forma as adjusted		7			90
Additional paid-in capital		1,889			139,156
Accumulated deficit		(49,927	)		(49,927	)
Total stockholders’ (deficit) equity		(48,031	)		89,319
Total capitalization	$	9,380		$	89,319		$

The pro forma as adjusted information above is illustrative only, and our capitalization following the closing of this offering will depend on the actual initial public offering price and other terms of this offering determined at pricing. Each $1.00 increase or decrease in the assumed initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase or decrease the

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pro forma as adjusted amount of each of cash and cash equivalents, additional paid-in capital, total stockholders’ (deficit) equity, and total capitalization by $         million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. Each increase or decrease of 1,000,000 shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would increase or decrease the pro forma as adjusted amount of each of cash and cash equivalents, additional paid-in capital, total stockholders’ (deficit) equity, and total capitalization by $         million, assuming no change in the assumed initial public offering price per share and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

The number of shares of our common stock shown as issued and outstanding in the table above is based on 92,072,630 shares of our common stock, which includes 2,301,266 shares of unvested early exercised stock options and the conversion of the 21,784,885 shares of Series C redeemable convertible preferred stock we issued and sold in February 2021, outstanding as of December 31, 2020, and excludes:

• 4,407,697 shares of common stock issuable upon the exercise of stock options outstanding as of December 31, 2020 under the 2012 Plan at a weighted average exercise price of $0.36 per share;

• 504,558 shares of common stock available for future issuance as of December 31, 2020 under the 2012 Plan; and

•              shares of common stock reserved for issuance under the 2021 Plan, which will become effective in connection with this offering.

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Dilution

If you invest in our common stock in this offering, you will experience immediate and substantial dilution in the pro forma as adjusted net tangible book value of your shares of common stock. Dilution in pro forma as adjusted net tangible book value represents the difference between the assumed initial price to the public per share of our common stock and the pro forma as adjusted net tangible book value per share of our common stock immediately after this offering.

Our historical net tangible book deficit as of December 31, 2020 was $(48.0) million, or $(5.18) per share of common stock. Our historical net tangible book deficit is the amount of our total tangible assets less our total liabilities and the carrying value of our redeemable convertible preferred stock, which is not included within stockholders’ (deficit) equity. Historical net tangible book deficit per share represents historical net tangible book deficit divided by the 9,269,749 shares of common stock outstanding as of December 31, 2020, which includes 2,301,266 shares of unvested early exercised stock options.

Our pro forma net tangible book value as of December 31, 2020 was $89.3 million, or $0.97 per share of common stock. Pro forma net tangible book value represents the amount of our total tangible assets less our total liabilities, after giving effect to (i) our issuance and sale in February 2021 of 21,784,885 shares of Series C redeemable convertible preferred stock for gross proceeds of $80.0 million, and (ii) the automatic conversion of all outstanding shares of our redeemable convertible preferred stock into an aggregate of 82,802,881 shares of common stock upon the closing of this offering. Pro forma net tangible book value per share represents pro forma net tangible book value divided by the total number of shares outstanding as of December 31, 2020, which includes 2,301,266 shares of unvested early exercised stock options, after giving effect to the pro forma adjustments described above.

After giving further effect to our issuance and sale of              shares of our common stock in this offering at an assumed initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us, our pro forma as adjusted net tangible book value as of December 31, 2020 would have been $         million, or $         per share. This represents an immediate increase in pro forma as adjusted net tangible book value per share of $         to existing stockholders and immediate dilution of $         in pro forma as adjusted net tangible book value per share to new investors purchasing common stock in this offering. Dilution per share to new investors is determined by subtracting pro forma as adjusted net tangible book value per share after this offering from the assumed initial public offering price per share paid by new investors.

The following table illustrates this dilution on a per share basis to new investors:

Assumed initial public offering price per share				$
Historical net tangible book deficit per share as of December 31, 2020	$	(5.18	)
Increase per share attributable to the pro forma adjustments described above		6.15
Pro forma net tangible book value per share as of December 31, 2020		0.97
Increase in pro forma as adjusted net tangible book value per share attributable to new investors purchasing common stock in this offering
Pro forma as adjusted net tangible book value per share after this offering
Dilution per share to new investors purchasing common stock in this offering				$

The dilution information discussed above is illustrative only and will change based on the actual initial public offering price and other terms of this offering determined at pricing. A $1.00 increase (decrease) in the

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assumed initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) our pro forma as adjusted net tangible book value per share after this offering by $         and dilution per share to new investors purchasing common stock in this offering by $        , assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. We may also increase or decrease the number of shares we are offering. An increase of 1,000,000 shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would increase our pro forma as adjusted net tangible book value per share after this offering by $         and decrease the dilution per share to new investors purchasing common stock in this offering by $        , assuming no change in the assumed initial public offering price per share and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. A decrease of 1,000,000 shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would decrease our pro forma as adjusted net tangible book value per share after this offering by $         and increase the dilution per share to new investors purchasing common stock in this offering by $        , assuming no change in the assumed initial public offering price and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

If the underwriters exercise their option to purchase additional shares in full, our pro forma as adjusted net tangible book value per share after this offering would be $        , representing an immediate increase in pro forma as adjusted net tangible book value per share of $         to existing stockholders and immediate dilution in pro forma as adjusted net tangible book value per share of $         to new investors purchasing common stock in this offering, assuming an initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us.

The following table summarizes, as of December 31, 2020, on the pro forma as adjusted basis described above, the total number of shares of common stock purchased from us on an as converted to common stock basis, the total consideration paid or to be paid and the average price per share paid or to be paid by existing stockholders and by new investors in this offering at an assumed initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, before deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. As the table shows, new investors purchasing common stock in this offering will pay an average price per share substantially higher than our existing stockholders paid.

	Shares purchased			Total consideration			Average price per share
	Number	Percent		Amount	Percentage
Existing stockholders			%	$		%	$
Investors participating in this offering							$
Total			100.0%		$	100.0%

A $1.00 increase (decrease) in the assumed initial public offering price of $         per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the total consideration paid by new investors by $         million and, in the case of an increase, would increase the percentage of total consideration paid by new investors by              percentage points and, in the case of a decrease, would decrease the percentage of total consideration paid by new investors by              percentage points, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same. An increase (decrease) of 1,000,000 shares in the number of shares offered by us, as set forth on the cover page of this prospectus, would increase (decrease) the total consideration paid by new investors by $         million and, in the case of an increase, would increase the percentage of total consideration

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paid by new investors by                percentage points and, in the case of a decrease, would decrease the percentage of total consideration paid by new investors by                percentage points, assuming no change in the assumed initial public offering price.

The table above assumes no exercise of the underwriters’ option to purchase additional shares in this offering. If the underwriters’ option to purchase additional shares is exercised in full, the number of shares of our common stock held by existing stockholders would be reduced to    % of the total number of shares of our common stock outstanding after this offering, and the number of shares of common stock held by new investors purchasing common stock in this offering would be increased to    % of the total number of shares of our common stock outstanding after this offering.

The tables and discussion above are based on the number of shares of our common stock outstanding as of December 31, 2020, which includes 2,301,266 shares of unvested early exercised stock options and the conversion of the 21,784,885 shares of Series C redeemable convertible preferred stock we issued and sold in February 2021, and excludes:

• 4,407,697 shares of common stock issuable upon the exercise of stock options outstanding as of December 31, 2020 under the 2012 Plan at a weighted average exercise price of $0.36 per share;

• 504,558 shares of common stock available for future issuance as of December 31, 2020 under the 2012 Plan; and

•                  shares of common stock reserved for issuance under the 2021 Plan, which will become effective in connection with this offering.

To the extent that outstanding stock options are exercised, new stock options are issued, or we issue additional shares of common stock in the future, there will be further dilution to new investors. In addition, we may choose to raise additional capital because of market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. If we raise additional capital through the sale of equity or convertible debt securities, the issuance of these securities could result in further dilution to our stockholders.

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Selected financial data

The following tables set forth our selected financial data for the periods indicated. We have derived the consolidated statements of operations data for the years ended December 31, 2020 and 2019, and the consolidated balance sheet data as of December 31, 2020 and 2019, from our audited consolidated financial statements included elsewhere in this prospectus. Our historical results are not necessarily indicative of the results that should be expected for any future period. You should read the following selected consolidated financial data together with our consolidated financial statements and the related notes included elsewhere in this prospectus and the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” section of this prospectus.

	Years ended December 31,
	2020			2019
	(in thousands, except share and per share data)
Consolidated Statements of Operations Data:
Grant revenue	$	—		$	8
Operating expenses:
Research and development		16,765			12,768
General and administrative		4,178			3,345
Total operating expenses		20,943			16,113
Loss from operations		(20,943	)		(16,105	)
Total other income		120			1,061
Net loss	$	(20,823	)	$	(15,044	)
Net loss attributable to common stockholders—basic and diluted(1)	$	(20,823	)	$	(15,044	)
Net loss per share—basic and diluted(1)	$	(3.99	)	$	(3.42	)
Weighted average common stock outstanding—basic and diluted(1)		5,217,910			4,397,374
Pro forma net loss per share attributable to common stockholders—basic and diluted(1)	$	(0.31	)
Pro forma weighted average common shares outstanding—basic and diluted(1)		66,235,906

(1) See Note 11 to our audited consolidated financial statements appearing elsewhere in this prospectus for details on the calculation of basic and diluted net loss per share attributable to common stockholders. The unaudited pro forma basic and diluted weighted-average common shares outstanding used in the calculation of unaudited pro forma basic and diluted net loss per share attributable to common stockholders for the year ended December 31, 2020 have been prepared to give effect to the issuance of 21,784,885 shares of our Series C redeemable convertible preferred stock in February 2021 and to give effect, upon a qualified initial public offering, to the automatic conversion of all outstanding shares of redeemable convertible preferred stock into common stock as if the proposed initial public offering had occurred on the later of the beginning of each period or the issuance date of the redeemable convertible preferred stock.

	December 31,
	2020			2019
	(in thousands)
Consolidated Balance Sheet Data:
Cash and cash equivalents	$	10,938		$	29,012
Working capital(1)		8,994			28,465
Total assets		13,735			31,369
Redeemable convertible preferred stock		57,411			57,411
Total stockholders’ deficit		(48,031	)		(28,336	)

(1) We define working capital as current assets less current liabilities.

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Management’s discussion and analysis of financial condition and results of operations

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our consolidated financial statements and the related notes to those statements included elsewhere in this prospectus. In addition to historical financial information, the following discussion and analysis contains forward-looking statements that involve risks, uncertainties and assumptions. Some of the numbers included herein have been rounded for the convenience of presentation. Our actual results may differ materially from those anticipated in these forward-looking statements as a result of many factors, including those discussed under “Risk Factors” and elsewhere in this prospectus.

Overview

We are a clinical-stage biotechnology company focused on developing and commercializing the next-generation of precision oncology medicines that inhibit DNA damage repair and cause cancer cell death through a therapeutic strategy known as synthetic lethality. Synthetic lethality represents a clinically validated approach to drug development and arises when there is a deficiency in either of two conditions that are tolerable alone in cells but lethal together. Our lead program, CYT-0851, as well as our next generation drug candidate CYT-1853, exploits a novel gain-of-function synthetically lethal relationship between overexpression of a family of DNA damaging genes called cytidine deaminases, or CDs, and functional inhibition of homologous recombination, or HR, a DNA repair pathway critical for the survival of some cancers. CYT-0851 is a novel, potentially first-in-class, oral small molecule inhibitor of RAD51-mediated HR. We are investigating CYT-0851 in a phase 1/2 trial in adult patients with hematologic malignancies and solid tumors, and have observed encouraging preliminary single agent activity in the dose escalation portion of the trial. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors. We also plan to develop CYT-0851 in additional tumor settings as both a monotherapy and in combination with approved cancer therapeutics and plan to initiate dosing in a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021.

Since our inception in 2012, we have focused primarily on organizing and staffing our company, business planning, raising capital, establishing our intellectual property portfolio and performing research and development of novel therapeutics. We do not have any drug candidates approved for sale and have not generated any revenue from product sales. Since our inception, we have funded our operations primarily with proceeds from the sale of redeemable convertible preferred stock and have raised an aggregate of approximately $61.0 million of gross proceeds from the sale of redeemable convertible preferred stock as of December 31, 2020. In February 2021, we completed the sale of our Series C redeemable convertible preferred stock, or Series C Preferred Stock, for gross proceeds of $80.0 million.

We have incurred significant operating losses since inception, including net losses of $20.8 million and $15.0 million for the years ended December 31, 2020 and 2019, respectively. As of December 31, 2020, we had an accumulated deficit of $49.9 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations. We expect to continue to generate operating losses and negative operating cash flows for the foreseeable future as we:

• continue the research and development of our drug candidates;

• initiate and conduct additional preclinical studies and clinical trials for our drug candidates;

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• further develop and refine the manufacturing processes for our drug candidates;

• seek regulatory approvals and pursue commercialization for any of our drug candidates that successfully complete clinical trials;

• seek to identify and validate additional drug candidates and their associated biomarkers;

• obtain, maintain, protect and enforce our intellectual property portfolio;

• seek to attract and retain new and existing skilled personnel;

• acquire or in-license other drug candidates and technologies;

• create additional infrastructure to support our operations as a public company and incur increased legal, accounting, investor relations and other expenses; and

• experience delays or encounter issues with any of the above.

We will not generate any revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for one or more of our drug candidates, if ever. If we obtain regulatory approval for any of our drug candidates, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing and distribution.

Furthermore, following the closing of this offering, we expect to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses that we did not incur as a private company. As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy, as we advance our drug candidates through clinical development, seek regulatory approval, prepare for and, if any of our drug candidates are approved, proceed to commercialization and operate as a public company. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions.

If we are unable to obtain funding, we will be forced to delay, reduce or eliminate some or all of our research and development programs, product portfolio expansion and ultimate commercialization efforts, which could adversely affect our business prospects, or we may be unable to continue operations. Although we continue to pursue these plans, there is no assurance that we will be successful in obtaining sufficient funding on terms acceptable to us to fund continuing operations, if at all.

As of December 31, 2020, we had cash and cash equivalents of $10.9 million. We believe that our existing cash and cash equivalents as of December 31, 2020, and the $80.0 million of gross proceeds from our Series C Preferred Stock financing in February 2021, together with the anticipated net proceeds from this offering will enable us to fund our operating expenses and capital expenditure requirements through             . We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “—Liquidity and Capital Resources.”

COVID-19 business update

In response to the ongoing COVID-19 pandemic, we established a cross-functional task force and have implemented business continuity plans designed to address and mitigate the impact of the COVID-19 pandemic on our employees and our business, including our clinical trials. Our operations are considered an essential business and we have been allowed to continue operating under current governmental restrictions during this

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period. We have taken measures to secure our research and development activities, while our work in laboratories and facilities has been organized to reduce risk of COVID-19 transmission. The extent of the impact of the COVID-19 pandemic on our business, operations and clinical development timelines and plans remains uncertain, and will depend on certain developments, including the duration and spread of the outbreak and its impact on our clinical trial enrollment, trial sites, contract research organizations, or CROs, contract manufacturing organizations, or CMOs, and other third parties with whom we do business, as well as its impact on regulatory authorities and our key scientific and management personnel. While we are experiencing limited financial impacts at this time, given the global economic slowdown, the overall disruption of global healthcare systems and the other risks and uncertainties associated with the pandemic, our business, financial condition and results of operations ultimately could be materially adversely affected. We continue to closely monitor the COVID-19 pandemic as we evolve our business continuity plans, clinical development plans and response strategy.

Components of results of operations

Revenue

All of our revenue has been derived from our grants from the National Institutes of Health, or NIH. In May 2019, the project period expired and the grants were completed and terminated. To date, we have not generated any revenue from product sales. If our development efforts for our drug candidates and preclinical programs are successful and result in regulatory approval, we may generate revenue in the future from product sales.

Operating expenses

Research and development expenses

Research and development expenses consist primarily of costs incurred in connection with the preclinical and clinical development and manufacture of our drug candidates, and include:

• personnel-related expenses, including salaries, bonuses, benefits, stock-based compensation and other related costs for individuals involved in research and development activities;

• external research and development expenses incurred under agreements with CROs as well as investigative sites and consultants that conduct our clinical trials and other scientific development services;

• costs incurred under agreements with CMOs for developing and manufacturing material for our preclinical studies and clinical trials;

• costs of outside consultants, including their fees, stock-based compensation and related travel expenses;

• costs related to compliance with regulatory requirements;

• costs of laboratory supplies and acquiring, developing and manufacturing study materials; and

• facilities and other allocated expenses, which include direct and allocated expenses for rent, insurance and other operating costs.

Costs for external development activities are recognized based on an evaluation of the progress to completion of specific tasks using information provided to us by our vendors and our clinical investigative sites. Payments for these activities are based on the terms of the individual agreements, which may differ from the pattern of costs incurred, and are reflected in our consolidated financial statements as prepaid or accrued research and development expenses. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses and expensed as the related goods are delivered or the services are performed.

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A significant portion of our research and development costs have been external costs, which we track on a program-by-program basis after a clinical drug candidate has been identified. Our internal research and development costs are primarily personnel-related costs, internal lab costs and other indirect costs. The majority of our external research and development expenses to date have been incurred in connection with CYT-0851.

We do not allocate employee costs, costs associated with our discovery efforts, and facilities, including depreciation or other indirect costs, to specific programs because these costs are deployed across multiple programs and, as such, are not separately classified. We use internal resources and third-party consultants primarily to conduct our research and discovery activities as well as for managing our process development, manufacturing and clinical development activities.

The successful development of our drug candidates is highly uncertain. We plan to substantially increase our research and development expenses for the foreseeable future as we continue our existing clinical trial, initiate future clinical trials for our drug candidates and continue to discover and develop additional drug candidates. Therefore, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts that will be necessary to complete the development and commercialization of our future drug candidates. We are also unable to predict when, if ever, material net cash inflows will commence from the sale of CYT-0851 or potential future drug candidates, if approved. This is due to the numerous risks and uncertainties associated with developing drug candidates, including the uncertainty of:

• the scope, rate of progress and expenses of our ongoing research activities and clinical trials and other research and development activities;

• successful patient enrollment in, and the initiation and completion of, clinical trials;

• establishing an appropriate safety profile;

• whether our drug candidates show safety and efficacy in our clinical trials;

• receipt of marketing approvals from applicable regulatory authorities;

• establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers;

• obtaining, maintaining, protecting and enforcing patent and trade secret protection and regulatory exclusivity for our drug candidates;

• commercializing drug candidates, if and when approved, whether alone or in collaboration with others; and

• continued acceptable safety profile of the products following any regulatory approval.

Any changes in the outcome of any of these variables with respect to the development of our drug candidates in preclinical and clinical development could mean a significant change in the costs and timing associated with the development of these drug candidates. We may never succeed in achieving regulatory approval for any of our drug candidates. We may obtain unexpected results from our clinical trials. We may elect to discontinue, delay or modify clinical trials of some drug candidates or focus on others. For example, if the FDA or another regulatory authority were to delay our planned start of clinical trials or require us to conduct clinical trials or other testing beyond those that we currently expect or if we experience significant delays in enrollment in any of our planned clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development of that drug candidate.

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General and administrative expenses

General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our executive, finance, corporate and business development and administrative functions. General and administrative expenses also include professional fees for legal, patent, accounting, auditing, tax and consulting services, and facility-related expenses, which include direct depreciation costs and allocated expenses for rent and maintenance of facilities and other operating costs.

We expect that our general and administrative expenses will increase in the future as we increase our general and administrative headcount to support our continued research activities and development of our drug candidates. We also expect that we will incur significantly increased accounting, audit, legal, regulatory, compliance and director and officer insurance costs as well as investor and public relations expenses associated with operating as a public company.

Other income

Change in fair value of preferred stock tranche obligation

Other income primarily consists of fluctuations in the fair value of our preferred stock tranche obligation. The preferred stock tranche obligation relates to our obligation to issue, and investors’ obligation to purchase, additional shares of our Series B Preferred Stock following the initial closing of our Series B Preferred Stock financing. This obligation was fully satisfied in July 2019 when the third and final tranche of the Series B Preferred Stock was closed.

Interest income

Other income includes interest income, which consists of interest earned on cash equivalents that generate interest on a monthly basis.

Results of operations

Comparison of the years ended December 31, 2020 and 2019

The following table summarizes our results of operations:

	Years ended December 31,						Change
(in thousands)	2020			2019
Grant revenue	$	—		$	8		$	(8	)
Operating expenses:
Research and development		16,765			12,768			3,997
General and administrative		4,178			3,345			833
Total operating expenses		20,943			16,113			4,830
Loss from operations		(20,943	)		(16,105	)		(4,838	)
Other income:
Other income		120			246			( 126	)
Change in preferred stock tranche obligations		—			815			(815	)
Total other income		120			1,061			(941	)
Net loss	$	(20,823	)	$	(15,044	)	$	(5,779	)

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Revenue

We recognized grant revenue of approximately $8,000 for the year ended December 31, 2019 under the NIH grants. No revenue was recognized for the year ended December 31, 2020 as a result of the completion of the NIH grants in May 2019.

Research and development expenses

The following table summarizes our research and development costs for each of the periods presented:

	Years ended December 31,
(in thousands)	2020		2019		Change
Direct research and development expenses by program:
RAD51-mediated HR inhibitor programs	$	9,627	$	8,442	$	1,185
Unallocated research and development expenses:
Personnel expenses (including stock-based compensation)		4,795		3,556		1,239
Other expenses		2,343		770		1,573
Total research and development expenses		$16,765	$	12,768	$	3,997

Research and development expenses were $16.8 million for the year ended December 31, 2020, which increased by $4.0 million from $12.8 million for the year ended December 31, 2019. The increase in research and development expenses was primarily attributable to the following:

• a $1.2 million increase in costs related to our RAD51-mediated HR inhibitor programs driven by the continued development of CYT-0851, our lead drug candidate, specifically due to the advancement of our ongoing clinical trial, as well as preclinical costs related to CYT-1853;

• a $1.6 million increase in other research and development operational expenses, including facilities and lab-related costs and insurance driven by the increase in headcount, as well as costs related to our discovery efforts; and

• a $1.2 million increase in personnel-related costs, including stock-based compensation expense, primarily due to an increase in headcount.

General and administrative expenses

General and administrative expenses were $4.2 million for the year ended December 31, 2020, which increased by $0.8 million, from $3.3 million for the year ended December 31, 2019. The increase in general and administrative expenses was primarily attributable to the following:

• a $0.6 million increase in personnel costs, including stock-based compensation expense, primarily due to an increase headcount and external consultants;

• a $0.2 million increase other general and administrative expenses, including professional fees, facilities, rent and insurance costs.

Total other income

Total other income was $0.1 million for the year ended December 31, 2020, compared to $1.1 million for the year ended December 31, 2019. Total other income for the year ended December 31, 2019 is primarily related to

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changes in the fair value of the preferred stock tranche obligation of $0.8 million. The preferred stock tranche obligation was fully satisfied in July 2019 with the closing of the third tranche of our Series B Preferred Stock financing. Total other income also includes interest income on our cash equivalents, which are primarily invested in money market funds. During the years ended December 31, 2020 and 2019, interest income was $0.1 million and $0.2 million, respectively.

Liquidity and capital resources

Sources of liquidity

Since our inception, we have not recognized any product revenue and have incurred operating losses and negative cash flows from our operations. We have not yet commercialized any product and we do not expect to generate revenue from sales of any products for several years, if at all.

We have funded our operations primarily with proceeds from the sale of redeemable convertible preferred stock and have raised an aggregate of approximately $61.0 million from the sale of redeemable convertible preferred stock as of December 31, 2020. In February 2021, we completed a financing through the sale of our redeemable convertible Series C Preferred Stock for gross proceeds of $80.0 million.

Funding requirements

As of December 31, 2020, our cash and cash equivalents on hand were $10.9 million. We believe that our existing cash and cash equivalents as of December 31, 2020, together with the proceeds from our Series C Preferred Stock financing in February 2021, and the anticipated net proceeds from this offering will enable us to fund our operating expenses and capital expenditure requirements through         . We have based this estimate on assumptions that may prove to be wrong, and we could expend our capital resources sooner than we expect.

We expect to incur significant expenses and operating losses for the foreseeable future as we advance our drug candidates through preclinical and clinical development, seek regulatory approval and pursue commercialization of any approved drug candidates. We expect that our research and development and general and administrative costs will increase in connection with our planned research and development activities. In addition, upon the completion of this offering, we expect to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses that we did not incur as a private company. If we receive regulatory approval for any of our other drug candidates, we expect to incur significant commercialization expenses related to product manufacturing, sales, marketing and distribution, depending on where we choose to commercialize. We may also require additional capital to pursue in-licenses or acquisitions of other drug candidates.

Because of the numerous risks and uncertainties associated with research, development and commercialization of our drug candidates, we are unable to estimate the exact amount of our working capital requirements. Our future capital requirements will depend on many factors, including:

• the continuation, timing, costs, progress and results of our planned clinical trials of CYT-0851;

• the progress of preclinical development and possible clinical trials of our current earlier-stage programs;

• the scope, progress, results and costs of our research programs and preclinical development of any additional drug candidates that we may pursue;

• the development requirements of other drug candidates that we may pursue;

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• the outcome, timing and cost of meeting regulatory requirements established by the FDA and other regulatory authorities;

• the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our drug candidates for which we receive marketing approval;

• the cost of expanding, maintaining, protecting and enforcing our intellectual property portfolio, including filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights;

• the cost of defending potential intellectual property disputes, including patent infringement actions brought by third parties against us or any of our drug candidates;

• the extent to which we in-license or acquire rights to other products, drug candidates or technologies;

• the extent to which the impact of COVID-19 or other pandemics may delay the development of our drug candidates;

• our headcount growth and associated costs as we expand our research and development, increase our office space, and establish a commercial infrastructure; and

• the ongoing costs of operating as a public company.

Until such time, if ever, as we can generate substantial product revenue to support our cost structure, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations and other similar arrangements. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our shareholders could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common shareholders. Debt financing and equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise funds through collaborations or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or drug candidates or grant licenses on terms that may not be favorable to us and/or may reduce the value of our common stock. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market our drug candidates even if we would otherwise prefer to develop and market such drug candidates ourselves.

Cash flows

The following table summarizes our cash flows for each of the periods presented:

	Years ended December 31,
(in thousands)	2020			2019
Net cash used in operating activities	$	(18,539	)	$	(17,557	)
Net cash used in investing activities		(850	)		(133	)
Net cash provided by financing activities		1,427			36,890
Net (decrease) increase in cash, cash equivalents and restricted cash	$	(17,962	)	$	19,200

Operating activities

Net cash used in operating activities for the year ended December 31, 2020 was $18.5 million, primarily due to our net loss of $20.8 million, partially offset by non-cash charges of depreciation expense of $0.4 million, stock-

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based compensation expense of $0.5 million and changes in operating assets and liabilities, including a $1.0 million increase in our accounts payable, $0.1 million increase in accrued expenses, a $0.1 million increase in deferred rent and $0.2 million decrease in prepaid expenses and other current assets.

Net cash used in operating activities for the year ended December 31, 2019 was $17.6 million, primarily due to our net loss of $15.0 million and changes in our working capital of $2.2 million, including a $1.3 million increase in our prepaid expenses and other current assets and a $0.9 million decrease in accounts payable, as well as the decrease in the preferred stock tranche obligation of $0.8 million. These amounts were partially offset by non-cash charges of depreciation expense of $0.2 million and stock-based compensation expense of $0.2 million.

Investing activities

Net cash used in investing activities was $0.9 million and $0.1 million for the years ended December 31, 2020 and 2019, respectively, and resulted from our purchases of property and equipment.

Financing activities

Net cash provided by financing activities was $1.4 million for the year ended December 31, 2020, relating to stock option exercises, including $0.8 million from early exercises of stock options.

Net cash provided by financing activities was $36.9 million for the year ended December 31, 2019, consisting of $36.6 million of net proceeds from the issuances of Series B Preferred Stock in July 2019 and September 2019, and $0.3 million from stock option exercises.

Contractual obligations and commitments

The following table summarizes our commitments to settle contractual obligations as of December 31, 2020 (in thousands):

	Payments due by period
	Total		Less than 1 year		1-3 years		3-5 years		More than 5 years
Operating lease obligations	$	2,077	$	715	$	1,362	$	—	$	—
Total	$	2,077	$	715	$	1,362	$	—	$	—

Lease commitments

We have entered into an operating lease for rental space in Lexington, Massachusetts. The table above includes future minimum lease payments under the non-cancelable lease arrangement, which extends through October 2023.

Purchase and other obligations

We enter into contracts in the normal course of business with CROs and other third-party vendors for clinical trials and testing and manufacturing services. Most contracts do not contain minimum purchase commitments and are cancellable by us upon written notice. Payments due upon cancellation consist of payments for services provided or expenses incurred, including non-cancelable obligations of our service provided up to one year after the date of cancellation. These payments are not included in the table above as the amount and timing of such payments are not known.

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Critical accounting policies and estimates

Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States. The preparation of our consolidated financial statements and related disclosures requires us to make judgments, estimates and assumptions that affect the reported amounts of assets and liabilities, costs and expenses and the disclosure of contingent assets and liabilities in our financial statements. We base our estimates on historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions or conditions.

While our significant accounting policies are described in greater detail in Note 2 to our consolidated financial statements appearing at the end of this prospectus, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements.

Accrued research and development expenses

As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued research and development expenses as of each balance sheet date. This process involves reviewing open contracts and purchase orders, communicating with our personnel and vendors to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost. The majority of our service providers invoice us monthly in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers and make adjustments if necessary.

We base our expenses related to research and development activities on our estimates of the services received and efforts expended pursuant to quotes and contracts with vendors that conduct research and development on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the research and development expense. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid balance accordingly. Non-refundable advance payments for goods and services that will be used in future research and development activities are expensed when the activity has been performed or when the goods have been received rather than when the payment is made.

Although we do not expect our estimates to be materially different from amounts incurred, if our estimates of the status and timing of services performed differ from the actual status and timing of services performed, it could result in us reporting amounts that are too high or too low in any particular period.

Stock-Based compensation

We account for all share-based compensation awards granted as stock-based compensation expense at fair value. Our share-based payments include stock options and grants of common stock, restricted for vesting conditions. The measurement date for awards is the date of grant, and stock-based compensation costs are

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recognized as expense over the requisite service period, which is generally the vesting period, on a straight-line basis. Stock-based compensation expense is classified in the accompanying statements of operations based on the function to which the related services are provided. We recognize stock-based compensation expense for the portion of awards that have vested. Forfeitures are recorded as they occur.

The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option-pricing model, which requires inputs based on certain subjective assumptions, including the expected share price volatility, the expected term of the option, the risk-free interest rate for a period that approximates the expected term of the option, and our expected dividend yield. As there is currently no public market for our common shares, we determined the volatility for awards granted based on an analysis of reported data for a group of guideline companies that issued options with substantially similar terms. The expected term of our stock options granted to employees has been determined utilizing the “simplified” method for awards that qualify as “plain-vanilla” options. The expected volatility has been determined using a weighted-average of the historical volatility measures of this group of guideline companies.

The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant of the award for time periods approximately equal to the expected term of the award. We have not paid, and do not anticipate paying, dividends on our common shares; therefore, the expected dividend yield is assumed to be zero.

Determination of the fair value of common stock

As there has been no public market for our common stock to date, the estimated fair value of our common stock has been determined by our board of directors utilizing the valuation of our company’s enterprise value determined by a third-party valuation expert, and in accordance with the guidance outlined in the American Institute of Certified Public Accountants Technical Practice Aid, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (the Practice Aid).

In addition to considering the results of the third-party valuations, our board of directors considered various objective and subjective factors to determine the fair value of our common stock as of each grant date, which may be a date later than the most recent third-party valuation date, including:

• the prices at which we sold preferred stock and the superior rights and preferences of the preferred stock relative to our common stock at the time of each grant;

• the progress of our research and development efforts, including the status of preclinical studies and ongoing and planned clinical trials for our RAD51-mediated HR inhibitor programs;

• the lack of liquidity of our equity as a private company;

• our stage of development and business strategy and the material risks related to our business and industry;

• the achievement of enterprise milestones;

• the valuation of publicly traded companies in the life sciences and biotechnology sectors, as well as recently completed mergers and acquisitions of peer companies;

• any external market conditions affecting the biotechnology industry, and trends within the biotechnology industry;

• the likelihood of achieving a liquidity event for the holders of our preferred stock and common stock, such as an IPO, or a sale of our company, given prevailing market conditions; and

• the analysis of IPOs and the market performance of similar companies in the biopharmaceutical industry.

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There are significant judgments and estimates inherent in these valuations. These judgments and estimates include assumptions regarding our future operating performance, the stage of development of our drug candidates, the timing of a potential IPO or other liquidity event and the determination of the appropriate valuation methodology at each valuation date. The assumptions underlying these valuations represent management’s best estimates, which involve inherent uncertainties and the application of management judgment. As a result, if factors or expected outcomes change and we use significantly different assumptions or estimates, our stock-based compensation expense could be materially different. Following the completion of this offering, the fair value of our common stock will be determined based on the quoted market price of our common stock.

Options granted

The following table sets forth, by grant date, the number of shares underlying options granted from January 1, 2020 through the date of this prospectus, the per share exercise price of the options, the fair value per share of common stock on each grant date and the estimated per share fair value of the options granted during the period:

Grant date	Number of common shares subject to options granted		Exercise price per common share(1)		Fair value per common share at grant date(1)		Weighted average estimated per-share options(2)
February 25, 2020		990,000	$	0.35	$	0.35	$	0.26
March 24, 2020		1,481,000	$	0.35	$	0.35	$	0.26
June 13, 2020		563,500	$	0.35	$	0.35	$	0.26
July 22, 2020		1,265,000	$	0.35	$	0.35	$	0.26
September 23, 2020		15,000	$	0.35	$	0.35	$	0.26
December 10, 2020		605,000	$	0.49	$	0.49	$	0.37
December 22, 2020		145,000	$	0.49	$	0.49	$	0.37
February 22, 2021		4,149,782	$	2.08	$	2.08	$	1.58

(1) The exercise price per share of common stock and the fair value of our common stock represents the fair value of our common stock on the date of grant, as determined by our board of directors, after taking into account our most recently available contemporaneous valuation of our common stock as well as additional factors that may have changed since the date of such contemporaneous valuation through the date of grant.

(2) The estimated per share fair value of options reflects the weighted average fair value of options granted on each grant date, determined using the Black-Scholes option-pricing model.

Off-balance sheet arrangements

We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under applicable SEC rules and regulations.

Recent accounting pronouncements

See Note 2 to our annual consolidated financial statements financial statements appearing elsewhere in this prospectus for a description of recent accounting pronouncements applicable to our financial statements.

Quantitative and qualitative disclosures about market risks

Interest rate risk

Our primary exposure to market risk is interest rate sensitivity, which is impacted by changes to the general level of U.S. interest rates, particularly because our cash equivalents are in the form of money market funds

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that are invested in U.S. Treasury securities. As of December 31, 2020, we had cash and cash equivalents of $10.9 million. Interest income is sensitive to changes in the general level of interest rates; however, due to the nature of these investments, an immediate 10% change in interest rates would not have a material effect on the fair market value of our investment portfolio.

As of December 31, 2020, and 2019, we had no debt outstanding, and therefore we are not subject to interest rate risk related to debt.

Foreign currency exchange risk

We are not currently exposed to significant market risk related to changes in foreign currency exchange rates.

Emerging growth company status

We are an “emerging growth company”, or EGC, under the Jumpstart Our Business Startups Act of 2012, or the JOBS Act. Section 107 of the JOBS Act provides that an EGC can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act of 1933, as amended, for complying with new or revised accounting standards. Thus, an EGC can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have elected to avail ourselves of delayed adoption of new or revised accounting standards and, therefore, we will be subject to the same requirements to adopt new or revised accounting standards as private entities.

As an EGC, we may, and intend to, take advantage of certain exemptions and reduced reporting requirements under the JOBS Act. Subject to certain conditions, as an EGC:

• we may present only two years of audited financial statements and only two years of related Management’s Discussion and Analysis of Financial Condition and Results of Operations;

• we may avail ourselves of the exemption from providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act;

• we may avail ourselves of the exemption from complying with any requirement that may be adopted by the Public Company Accounting Oversight Board, or PCAOB, regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, known as the auditor discussion and analysis;

• we may provide reduced disclosure about our executive compensation arrangements; and

• we may not require nonbinding advisory votes on executive compensation or stockholder approval of any golden parachute payments.

We will remain an EGC until the earliest of (i) the last day of the fiscal year following the fifth anniversary of the completion of this offering, (ii) the last day of the fiscal year in which we have total annual gross revenues of $1.07 billion or more, (iii) the date on which we have issued more than $1.0 billion in non-convertible debt during the previous rolling three-year period or (iv) the date on which we are deemed to be a large accelerated filer under the Securities Exchange Act of 1934, as amended, or the Exchange Act.

We are also a “smaller reporting company,” meaning that the market value of our stock held by non-affiliates plus the proposed aggregate amount of gross proceeds to us as a result of this offering is less than $700 million and our annual revenue was less than $100 million during the most recently completed fiscal year. We may continue to be a smaller reporting company after this offering if either (i) the market value of our stock held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100 million during the most

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recently completed fiscal year and the market value of our stock held by non-affiliates is less than $700 million. If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies. Specifically, as a smaller reporting company we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Report on Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation.

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Business

Overview

We are a clinical-stage biotechnology company focused on developing and commercializing the next-generation of precision oncology medicines that inhibit DNA damage repair and cause cancer cell death through a therapeutic strategy known as synthetic lethality. Synthetic lethality represents a clinically validated approach to drug development and arises when there is a deficiency in either of two conditions that are tolerable alone in cells but lethal together. Our lead program, CYT-0851, as well as our next generation drug candidate CYT-1853, exploits a novel gain-of-function synthetically lethal relationship between overexpression of a family of DNA damaging genes called cytidine deaminases, or CDs, and functional inhibition of homologous recombination, or HR, a DNA repair pathway critical for the survival of some cancers. CYT-0851 is a novel, potentially first-in-class, oral small molecule inhibitor of RAD51-mediated HR. We are investigating CYT-0851 in a phase 1/2 trial in adult patients with hematologic malignancies and solid tumors, and have observed encouraging preliminary single agent activity in the dose escalation portion of the trial. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors. We also plan to develop CYT-0851 in additional tumor settings as both a monotherapy and in combination with approved cancer therapeutics and plan to initiate dosing in a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021.

Cells have complex, coordinated DNA damage repair pathways to ensure genome integrity. Several DNA repair pathways have been identified as essential for repairing the myriad forms of DNA damage our cells experience, such as non-homologous end joining, or NHEJ, and HR. NHEJ repairs double stranded DNA, or dsDNA, breaks by directly rejoining the two broken ends, an error-prone pathway that can introduce DNA mutations. HR is critical for the error-free repair of dsDNA breaks by using the sister DNA strand as a template to restore the broken DNA strand to its original sequence. HR is thereby able to preserve the normal function of damaged genes by preventing the introduction of DNA mutations. Activity of this highly coordinated network of DNA damage sensing and repairing pathways is collectively called the DNA Damage Response, or DDR.

A hallmark feature of cancer cells is the accumulation of DNA mutations, many of which drive the aggressive characteristics of cancer cells, such as uncontrolled cell proliferation, invasion of surrounding tissues and, importantly, resistance to standard therapies. DNA damage, while a driver of normal cells becoming cancer cells, can trigger cell death when it accumulates to lethal levels. To survive, cancer cells become dependent on error-free DNA repair pathways, preventing them from reaching lethal levels of DNA damage. Consequently, they often become more vulnerable than normal cells to therapeutic inhibition of those same DNA repair pathways, which are made up of hundreds of individual proteins and potential drug targets. We initially focused on cancers that overexpress a DNA damaging enzyme, Activation-Induced Cytidine Deaminase, or AID, a member of the CD family, rendering them dependent on HR for their survival.

The physiological role of AID, expressed primarily in activated B cells of the immune system, is to augment our immune response to pathogens by enabling diverse antibody production. However, when AID is overexpressed, as it often is in certain forms of cancer, such as B-cell lymphomas, it leads to genome-wide DNA damage and collateral mutations. To avoid cell death, cancer cells frequently activate DNA damage repair pathways, including HR, to properly repair the harmful damage to genes that are vital for the cancer’s survival. This increased dependency on HR presents a therapeutic opportunity in those cancers overexpressing AID, including B cell lymphomas. Like AID, the Apolipoprotein B mRNA Editing Catalytic Enzymes, or APOBEC, genes, which are also members of the CD family, have been shown to induce cancer causing mutations when constitutively overexpressed and functionally dysregulated. The APOBEC3 genes are normally involved in anti-viral response mechanism and are induced downstream of interferon signaling in response to viral infections. They are also

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often highly expressed in cancers and are thought to play a major role in driving cancer progression in subsets of solid tumors, such as head and neck, breast and lung cancers.

Capitalizing on this therapeutic opportunity, we developed a platform to discover small molecule HR inhibitors, without regard to molecular target, based on the observation that AID-overexpressing B cells are dependent on HR for their survival. CYT-0851 is the result of extensive medicinal chemistry efforts optimizing early hits from this novel drug screening platform.

Our approach to drug discovery and development

We are using our expertise in DDR biology and a disciplined approach to select targets for other novel, differentiated drug discovery and development programs. Our approach includes:

• systematically prioritizing DDR targets based on our deep understanding of DDR biology, coupled with the mining of mutational information collected on diseased tissues and the analysis of results from both internal and external CRISPR-based genetic, chemical and cellular phenotypic synthetic lethality screens;

• elucidating synthetic lethality dependencies of our drug targets and using that information to molecularly define patient populations most likely to benefit from our therapies as a monotherapy, and maximizing tumor selectivity that limits side effects and allows our drugs to be used in combination with other standard anti-cancer therapies;

• developing potent, highly selective, well tolerated, small molecule therapies against these targets and evaluating them in biomarker-selected in vitro and in vivo model systems; and

• expeditiously progressing lead candidates through preclinical studies and into focused clinical trials in defined patient populations using a biomarker-guided approach.

Our core capabilities in discovery biology focusing on DNA damage repair has enabled us to move rapidly and efficiently from drug discovery to clinical development. We have the management team with the successful global registration experience to potentially advance our drug candidates to registration. In only three years, we progressed CYT-0851 from discovery to clinical proof of concept. In 2021, we intend to define the optimal development plan for potentially achieving accelerated approval of CYT-0851 initially as monotherapy in late lines of treatment for certain lymphomas and/or solid tumors. In addition, we may broaden the target patient population in both hematologic malignancies and solid tumors and move to earlier lines of treatment, either alone and/or in combination with standard-of-care therapies.

Our pipeline

The following chart summarizes our clinical product pipeline. We hold worldwide development and commercialization rights to our drug candidates.

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Our programs

Our lead program, CYT-0851, is a novel, oral, once-daily, potential first-in-class, small molecule inhibitor of RAD51-mediated HR with a potentially high therapeutic index. In the dose escalation portion of our ongoing phase 1/2 trial of CYT-0851, we have enrolled 37 patients as of March 16, 2021, and have an aggregated analysis on 23 of these patients from December 8, 2020. At this analysis, ten patients were considered response-evaluable, and we observed preliminary evidence of clinical benefit with four patients achieving stable disease, and two patients with diffuse large B-cell lymphoma, or DLBCL, and soft tissue sarcoma achieving a partial response. Of these 23 patients, 26% reported relatively mild (primarily grade 1 and 2) treatment-related adverse events and 74% did not report any treatment-related adverse events. This tolerable safety profile reported to date distinguishes CYT-0851 from most other approved cancer drugs and those in development that employ similar synthetically lethal strategies to treat cancer. We plan to advance CYT-0851 into monotherapy phase 2 expansion in seven tumor-specific patient groups beginning in the second half of 2021. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors.

To expand the potential of CYT-0851 beyond monotherapy use, we have conducted preclinical studies to explore combinations with a variety of standard-of-care anti-cancer drugs and have observed synergistic treatment effects. We believe the encouraging preclinical results in conjunction with the favorable monotherapy clinical activity and tolerability of CYT-0851 to date provide a strong rationale for the development of a combination therapy in the future. Many of these therapies work by exacerbating DNA damage in cancer cells, which puts stress on DDR pathways and potentially creates a synergistic opportunity with CYT-0851 treatment. We anticipate dosing the first patient in combination with other approved anti-cancer therapies in the second half of 2021.

To complement CYT-0851, we are developing CYT-1853 as a next generation inhibitor of RAD51-mediated HR. Importantly, in preclinical models, CYT-1853 is also synthetically lethal in CD-overexpressing cancer cells, is active across a range of cancer cell lines, and exhibits improved potency compared to CYT-0851. We are planning to complete IND-enabling studies in 2021 and to file an IND in 2022.

Furthermore, we have identified an undisclosed second target, a protein in one of the DNA repair pathways other than HR, as well as subsets of cancers that depend on this protein for their survival. We have identified a potential biomarker for use in candidate development and, ultimately, patient selection. Importantly, expression of this protein is prognostic, meaning patients whose cancer cells overexpress this protein generally have shorter survival compared to patients whose cancer cells do not. We are in the discovery stage of this program, and we anticipate reaching the drug candidate nomination stage and initiating IND-enabling studies in 2022.

Our management team

We have assembled a management team of biopharmaceutical industry veterans with extensive experience in developing novel oncology therapies, including advancing drug candidates from preclinical research through clinical development and ultimately regulatory approval and commercialization. Our team is led by our President and Chief Executive Officer, Markus Renschler, M.D., who has over 25 years’ experience at Celgene Corporation, Pharmion Corporation and Pharmacyclics in building successful biopharmaceutical companies, with direct involvement in developing and commercializing drugs such as Imbruvica^® (ibrutinib), REVLIMID^® (lenalidomide), POMALYST^® (pomalidomide), ABRAXANE^® (nab-paclitaxel) and VIDAZA^® (azacytidine). Paul Secrist, Ph.D., our Chief Scientific Officer, has over 25 years’ experience in drug discovery and pre-clinical development at OSI Pharmaceuticals, Aton Pharma, Merck Inc., and AstraZeneca, with direct involvement in the development of Zolinza^® (vorinostat) and Tarceva^® (erlotinib). Andrew Gengos, our Chief Business Officer, has

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over 25 years’ experience in strategic, operational, and financial roles at both emerging and established companies in the biopharmaceutical sector, including McKinsey & Company, Chiron, ImmunoCellular Therapeutics and Amgen Inc., where he led business development activities and closed multiple billions of dollars of M&A, licensing, and corporate venture capital transactions. Thomas O’Shea, Ph.D., our Senior Vice President of Clinical Pharmacology and Preclinical Development has over 25 years’ experience at Sanofi, Genzyme, AstraZeneca, Pharmacia and Searle & Co. Inc., with a proven track record of successfully driving preclinical research and development across diverse therapeutic areas, contributing to the successful global registration of several drugs including Cerdelga^® (eliglustat), Kynamro^® (mipomersen) and Mozobil^® (plerixafor).

We have raised more than $140 million of capital from a group of leading life sciences investors, including Novo Holdings, Droia Ventures, Venrock, Osage University Partners, Lightstone Ventures, RA Capital Management and Janus Henderson Investors, as well as Celgene Corporation, or Celgene, a global biotechnology company that merged with Bristol-Myers Squibb Company.

Strategy

Our goal is to be the leading biopharmaceutical company developing and commercializing next generation precision oncology medicines that inhibit DDR and cause cancer cell death through synthetic lethality. We employ an integrated drug discovery approach with a streamlined drug development process that leverages our team’s distinguished success bringing medicines to the market with the aim to build a patient-centric portfolio of effective cancer therapies.

The key elements of our strategy are to:

• Build upon the differentiated profile and encouraging preliminary single-agent activity of our lead drug candidate, CYT-0851, to rapidly advance it through clinical development and regulatory approval.    We designed CYT-0851 to have a highly selective and potent profile that may enable it to be a leading inhibitor of RAD51-mediated HR, if approved. We are currently in a phase 1/2 trial for both hematologic malignancies and solid tumors that overexpress CD/AID and, depending on the cancer type, we may develop a biomarker for patient enrichment. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors.

• Leverage CYT-0851’s favorable monotherapy clinical activity and tolerability to develop it in combination with DNA damaging drugs, such as chemotherapy or poly-ADP ribose polymerase, or PARP, inhibitors. In parallel with monotherapy development, we intend to evaluate CYT-0851 in combination with standard-of-care DNA damaging cancer drugs, such as chemotherapy and PARP inhibitors. Our preclinical data support such combinations and may expand our market opportunities not only into additional cancer types but also into earlier lines of therapy where chemotherapy continues to be a treatment standard. We plan to initiate dosing in a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021.

• Advance our next generation inhibitor of RAD51-mediated HR, CYT-1853, through clinical development and regulatory approval to complement CYT-0851.    We intend to leverage our experience with CYT-0851 to develop CYT-1853 as a monotherapy for various cancers. CYT-1853 is more than 10-fold more potent than CYT-0851 in cell-based assays, potentially allowing CYT-1853 to treat tumor types either where CYT-0851 lacks sufficient potency or where resistance to CYT-0851 has developed. CYT-1853 has demonstrated reduced potential for drug-drug interactions, or DDIs, and therefore may broaden its potential for combination therapy.

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We believe the ability of CYT-1853 to inhibit HR and promote synthetic lethality has the potential to deliver potent anti-tumor effects across a wide range of cancers and expect to complete IND-enabling studies in 2021 and file an IND in 2022.

• Utilize our deep understanding of DDR and tumor biology to identify novel drug candidates and expand our pipeline.    We will continue to build and direct our discovery platform of DDR biology and chemistry expertise to generate additional therapeutic programs. We have identified an undisclosed second target, a protein in one of the DNA repair pathways other than HR. This protein often is overexpressed in cancers and, when overexpressed, it is associated with shorter survival. We have also identified a potential biomarker for patient selection and anticipate reaching the drug candidate nomination stage to initiate IND-enabling studies in 2022. In addition to advancing this program, we will continue to focus our drug discovery effort on other potential DDR targets to exploit synthetic lethality in cancers.

• Maximize the value of our drug candidates and pipeline while selectively evaluating strategic collaborations.    We own all worldwide rights to our pipeline of precision-oncology programs, and we intend to commercialize our drug candidates, if approved, in key geographies. In the future, we may selectively enter into strategic collaborations around certain targets, drug candidates, disease areas or geographies if we believe these collaborations could maximize the value of our drug candidates.

Cancer treatments moving toward targeted therapeutics but unmet need remains

Advances in the molecular and genetic understanding of cancer have driven a fundamental shift away from cytotoxic chemotherapy treatments toward more targeted therapies that address aberrations in the cellular pathways and proteins necessary for cancer cell growth, proliferation and survival. These targeted therapies provide a precise method for treating the patients who are most likely to clinically benefit from them. For example, certain patients with lung cancer express mutated forms of epidermal growth factor receptor, or EGFR, which have been validated targets for EGFR-directed therapies. Other targeted therapies address dysregulated pathways that are shared among an entire disease specific population, such as the use of vascular endothelial growth factor inhibitors in renal cell carcinoma. Despite their successes, targeted therapies have had limited utility in those cancers that (1) have no identifiable therapeutic targets, (2) have an identifiable target, but it is not “druggable” given the limitations of current technologies, or (3) ultimately develop resistance through mutations, the use of alternative pathways or the loss of the target. Combining therapies and treating cancer through orthogonal pathways with multiple agents can limit the development of resistance to targeted therapies; however, the overlapping toxicity profile of many targeted agents has prevented their use in combination with chemotherapy, immunotherapy and/or radiation. We believe that DNA damage repair, essential for the survival of many cancer cells and for the progression of tumors, provides a unique opportunity to improve patient outcomes by expanding the number of addressable targets and allowing for combination with current standard-of-care therapies.

The importance of DNA damage repair

Deoxyribonucleic acid, or DNA, the often-called “blueprint of life” biomolecule found in chromosomes of all living organisms, is made up of two strands of deoxyribonucleic acids. DNA is constantly under barrage by DNA damaging radiation, including ultraviolet radiation in sunlight, carcinogens in tobacco smoke and even naturally occurring substances produced inside our cells during the normal processes of cell growth and division. This damage can occur on single or both strands of DNA, and it has been estimated that every cell in our body endures tens of thousands of DNA damaging events per day.

Cells have complex, coordinated DNA damage repair pathways to ensure genome integrity. Several DNA repair pathways have been identified as essential for repairing the myriad forms of DNA damage our cells experience,

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such as non-homologous end joining, or NHEJ, and homologous recombination, or HR. NHEJ repairs double stranded DNA, or dsDNA, breaks by directly rejoining the two broken ends, an error-prone pathway that can introduce DNA mutations. HR is critical for the error-free repair of dsDNA breaks by using the sister DNA strand as a template to restore the broken DNA strand to its original sequence. HR is thereby able to preserve the normal function of damaged genes by preventing the introduction of DNA mutations. Activity of this highly coordinated network of DNA damage sensing and repairing pathways is collectively called the DNA Damage Response, or DDR.

Multiple DNA repair pathways exist to sense and repair damaged DNA

Different DNA repair pathways sense and repair the myriad types of DNA damage that all cells incur daily. Some of the most well characterized DNA repair pathways shown above include HR, NHEJ, Micro-Homology Mediated End Joining, or MMEJ, Single Strand Annealing, or SSA, Base Excision Repair, or BER, Nucleotide Excision Repair, or NER, Translesion Synthesis, or TLS, as well as Mismatch Repair, or MMR, which proofreads and corrects DNA errors introduced during DNA replication.

Dependence on DNA damage repair creates a therapeutic opportunity in cancer

A hallmark feature of cancer cells is the accumulation of DNA mutations, many of which drive the aggressive characteristics of cancer cells, such as uncontrolled cell proliferation, invasion of surrounding tissues and, importantly, resistance to standard therapies. Although a driver of normal cells becoming cancer cells, unrepaired DNA damage can accumulate to lethal levels that trigger cell death. To survive, cancer cells become dependent on error-free DNA repair pathways, preventing them from reaching lethal levels of DNA damage. Consequently, they often become more vulnerable than normal cells to therapeutic inhibition of those same DNA repair pathways, which are made up of hundreds of individual proteins and potential drug targets. We initially focused on cancers that overexpress a DNA damaging enzyme, Activation-Induced Cytidine Deaminase, or AID, a member of the cytidine deaminase, or CD, family, rendering them dependent on HR for their survival. The figure below depicts how cells utilize DDR pathways to repair damaged DNA, and how the increased levels of DNA damage that cancer cells incur can make them more dependent on DNA damage repair and more sensitive to DDR-targeted therapy.

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Cancer cells become dependent on DNA damage repair pathways

By their nature, cancer cells suffer excessive DNA damage compared to normal cells, and this increases their dependence on DNA repair processes, such as HR, to prevent the accumulation of genome-wide, catastrophic levels of DNA damage that would otherwise trigger cell death. This dynamic creates the opportunity for a unique strategy to therapeutically target the cancer’s Achilles’ heel, the specific DDR pathway crucial for the cancer cell’s survival. By selectively inhibiting DNA repair, DDR-targeted cancer therapies can cause the massive accumulation of unrepaired DNA breaks in cancer cells, ultimately inducing cell death through a process known as mitotic catastrophe. Normal cells are often spared from cell death because they express a full complement of overlapping DNA repair pathways as well as fully functional cell cycle checkpoint safeguards—these pathways, sensing DNA damage, direct the cell to stop dividing until its DNA is properly repaired, thereby avoiding mitotic catastrophe.

Harnessing the therapeutic potential of synthetic lethality in DDR

Leveraging synthetic lethality is a potentially powerful approach in cancer drug discovery because it may lead to better tolerated therapies that preferentially kill cancer cells and it facilitates the identification of patient subpopulations most likely to respond to therapy. Synthetic lethality represents a clinically validated approach to drug development and arises when there is a deficiency in either of two conditions that are tolerable alone in cells but lethal together. As it relates to cancer therapeutics, a pre-existing, cancer-specific gene mutation might be a condition that is synthetically lethal with the therapeutic inhibition of a second target protein. The existence of the cancer-specific gene mutation makes the therapeutic intervention lethal to the cancer cells, but relatively innocuous to the normal cells that do not express the sensitizing mutation. Because DDR defects are common in nearly all cancers, DNA repair pathways are fertile areas to discover novel synthetic lethal targets for the development of effective targeted cancer therapies. Gene mutations are generally classified as either loss-of-function (inactivation of a tumor suppressor gene) or gain-of-function (activation of an oncogene) defects. While synthetic lethality is most frequently associated with loss-of-function conditions, it also can be applied to gain-of-function conditions.

A clinically validated example of loss-of-function synthetic lethality is the use of PARP inhibitors to treat a subset of tumors that harbor certain HR deficiencies. For example, in subsets of ovarian, breast, prostate, and pancreatic cancers, pre-existing mutations in the Breast Cancer Genes, or BRCA, functionally impair HR and render those cancer cells sensitive to treatment with PARP inhibitors. The co-existence of both conditions—the pre-existing loss-of-function BRCA mutation and the therapeutic targeting of PARP—creates synthetic lethality that leads to cancer specific cell death. The FDA and foreign regulatory authorities have approved four PARP inhibitors for the treatment of patients, including those with BRCA-mutant

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ovarian cancer, breast cancer, pancreatic cancer and metastatic castration-resistant prostate cancer. Global sales of PARP inhibitors in 2020 totaled more than $2.5 billion.

The success of PARP inhibitors has provided proof of concept for the therapeutic potential of using synthetic lethality as an approach to identify and develop clinically effective cancer therapies. It confirms that pre-existing defects in cancers (HR deficiencies) render cells sensitive to therapeutic inhibition of a DDR target (PARP) and at the same time provide the basis for a clinical biomarker to identify patients poised to respond to the therapy (e.g., BRCA gene mutations). The pivotal clinical trial of olaparib as maintenance therapy for patients with BRCA-mutant ovarian cancer demonstrated a 70% lower risk of disease progression or death when treated with olaparib compared to placebo. While the magnitude of this treatment effect represents substantial benefit for the subset of patients harboring BRCA mutations, only a small minority of patients with these cancers harbors such mutations. For example, only 10-15% of all ovarian cancer patients are estimated to harbor them. An unmet need remains for most patients without the BRCA mutation and for patients with cancers other than these four approved indications. In addition, patients with hematologic malignancies typically do not harbor BRCA mutations, and therefore PARP inhibitors are not approved for this use.

Discovery of a novel gain-of-function synthetically lethal relationship

Our lead program, CYT-0851, as well as our next generation drug candidate CYT-1853, exploits a novel gain-of-function synthetically lethal relationship between overexpression of CDs and functional inhibition of HR, a DNA repair pathway critical for the survival of some cancers.

AID is a member of a larger family of enzymes referred to as CDs. CDs are tightly regulated nucleic acid damaging enzymes that convert cytidine into uridine by removing an amine group, a process known as deamination. The deamination of cytidine to uridine in DNA creates base pair mismatching that fosters DNA mutations and dsDNA breaks that can lead to chromosomal translocations, known drivers of cancer, as depicted in the figure below.

Activation-induced cytidine deaminase induces DNA damage

The physiological role of AID, expressed primarily in activated B cells of the immune system, is to augment our adaptive immune response to pathogens by enabling diverse antibody production. AID and the DNA damage it induces at specific sites in our genome where antibody genes reside is critical to establishing a normal antibody response to infections. In normal B cells, AID is transiently expressed and tightly regulated to concentrate its

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mutagenic action on the DNA encoding our antibody genes, a beneficial effect that ultimately improves our immunity. When AID becomes constitutively overexpressed and dysregulated, as it often does in certain forms of cancer, such as B cell lymphomas, it leads to genome-wide DNA damage and collateral mutations beyond our antibody genes. To avoid mitotic catastrophe, cancer cells frequently rely on DNA damage repair pathways, including HR, to properly repair the harmful damage incurred to genes vital for the cancer’s survival. This increased dependency on HR presents a therapeutic opportunity in those cancers overexpressing AID, including B cell lymphomas.

AID induces physiological (beneficial) and pathological (harmful) DNA damage

Recognizing this therapeutic opportunity, we developed a platform to discover small molecule HR inhibitors, without regard to molecular targets, based on the observation that AID-overexpressing B cells were more sensitive to HR inhibition than B cells not expressing AID. We applied extensive medicinal chemistry efforts optimizing early hits from this novel drug screening platform to discover CYT-0851. CYT-0851 and its analogs are proprietary small molecules that have been claimed in two issued U.S. patents.

Synthetic lethality opportunities for CYT-0851 beyond AID and B cell lymphomas

Like AID, the other Apolipoprotein B mRNA Editing Catalytic Enzymes, or APOBEC, genes, which are also members of the CD family, have been shown to induce cancer causing mutations when constitutively overexpressed and functionally dysregulated. The APOBEC3 genes are normally involved in viral immunity and are induced downstream of interferon signaling in response to viral infections. They are also often highly expressed in cancers and are thought to play a major role in driving cancer progression in subsets of solid tumors, such as head and neck, breast and lung cancers. As expected, B cell lymphomas and leukemias generally express high levels of many of the CD genes, but importantly, several solid tumor types also express high levels of AID or individual APOBEC3 genes. This observation supports our belief that therapies targeting HR and exploiting the synthetic lethality relationship created by AID/APOBEC3 overexpression might have broad utility across both hematologic malignancies and solid tumor cancers.

Beyond CD gene overexpression, it is plausible that additional cellular conditions exist in subsets of cancers, such as specific defects in alternative DNA damage repair pathways or cell cycle checkpoint genes that create synthetic lethality with HR inhibition. Such conditions may provide additional therapeutic opportunities for our lead program and are being explored.

Synthetic lethality opportunities for CYT-0851 in combination therapy

Monotherapy treatment relying on the synthetic lethality described above requires pre-existing, intrinsic defects in the cancer cells. Combination therapy can create the synthetic lethality, without any pre-existing

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defects in DDR in the cancer, through the exogenous induction of DNA damage by chemotherapy or radiation therapy combined with therapeutic inhibition of HR. Such combination therapy potentially could be used broadly across cancer types and with multiple classes of chemotherapy drugs and other DDR agents such as PARP inhibitors.

Strong rationale to explore multiple drug combinations in a broad range of cancers

The clinical utility of such a combination approach in the past has been limited by the overlapping toxicities of DDR inhibitors, such as PARP inhibitors or other experimental agents, and chemotherapy, particularly with respect to myelosuppression. We believe that the observed safety profile of CYT-0851, particularly the lack of myelosuppression observed to date both preclinically and clinically, may allow such combinations to be tolerable. Finally, synthetic lethality may also be achieved through inhibition of PARP and inhibition of HR with a drug such as CYT-0851. Each drug inhibits different DNA repair pathways, that when simultaneously inhibited, could create synthetic lethality in cancer cells that have high levels of endogenous DNA damage.

CYT-0851: A drug candidate with broad therapeutic potential in HR-dependent cancers

Program overview

Our lead drug candidate, CYT-0851, is a potent and selective oral small molecule inhibitor of RAD51-mediated HR that we are developing for the treatment of hematologic malignancies and solid tumors. Cancer cells require HR for the error-free repair of dsDNA breaks, the most harmful and difficult type of DNA damage to repair. Inhibiting this non-redundant DNA repair pathway drives synthetic lethality in cancer cells that are dependent on HR for survival.

In preclinical studies, CYT-0851 has demonstrated potent anti-tumor activity, cancer cell selectivity, and favorable safety and pharmacokinetic profiles that support its potential as a novel therapy that could address the serious unmet need in multiple cancers. We efficiently and expeditiously advanced CYT-0851 into the clinic with a development strategy designed to support the potential regulatory approval for treatment of patients with certain hematologic malignancies or solid tumors.

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We are currently conducting a phase 1/2 trial, which we refer to as Study CYT-0851-01, enrolling patients with either hematologic malignancies or solid tumors for monotherapy treatment. The first portion of the trial will establish the dose and schedule of CYT-0851 administration as a monotherapy. The second part of the trial will evaluate the preliminary anti-tumor activity in various hematologic malignancies and solid tumors including diffuse large B-cell lymphoma, or DLBCL, mantle cell lymphoma, or MCL, multiple myeloma, or MM, triple negative breast cancer, ovarian cancer, soft tissue sarcoma and pancreatic cancer. This study is intended to provide these necessary insights to support our broad development program of CYT-0851.

In the dose-escalation portion of our trial to date, CYT-0851 has demonstrated the potential for achieving anti-tumor effects in a variety of advanced solid tumors or hematologic malignancies and maintained a favorable safety profile. CYT-0851 has the potential to be the first DDR-targeting drug to be approved in the United States for hematologic malignancies. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors.

In the second half of 2021, we also intend to initiate the evaluation of CYT-0851 in combination with standard-of-care cancer drugs, which may include chemotherapy or PARP inhibitors, for the treatment of either hematologic malignancies or solid tumors.

Hematologic malignancies and the current standard of care

Hematologic malignancies are a heterogeneous group of disorders, characterized as cancers arising from cells originating in the bone marrow or lymphoid tissues. Given their cell of origin, these cancers readily spread throughout the body through the cardiovascular and lymphatic systems and typically require a systemic approach for treatment and cannot be cured by surgery or localized radiation therapy in most cases. Certain diseases such as DLBCL, the most common type of non-Hodgkin lymphoma, or NHL, are potentially curable with aggressive therapies even in the most advanced setting, while other disorders such as MCL, follicular lymphoma, or FL, and MM are treated with the goal of long-term disease and symptom control because cure typically has not been possible. The first line of treatment for the majority of these disorders consists of combination therapy comprised of chemotherapy, targeted agents and/or radiation. When the disease progresses, commonly referred to as relapsed or refractory disease, alternative regimens and combinations are employed, but typically with reduced rates of success and shorter duration of benefit at each progression until the patient exhausts their therapeutic options, is no longer in a physical condition to receive treatment or elects to discontinue active treatment of their disease.

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Hematologic malignancies market opportunity

In 2021, according to the American Cancer Society, 186,000 newly diagnosed hematologic malignancy cases and more than 57,000 deaths are expected in the United States. MM and NHL are expected to account for 35,000 and more than 81,000 of these new cases, respectively. Within NHL, DLBCL, FL and MCL are expected to account for about 59%, or 48,000, of new cases. These four indications are expected to account for more than an estimated 20,000 deaths in 2021, indicative of the large ongoing unmet need.

Malignancy	2021 estimated incidence		2021 estimated mortality
All Hematologic		186,400		57,800
MM		35,000		12,400
NHL		81,560		20,720
DLBCL		25,000		5,300
FL		18,000		1,650
MCL		4,900		NA

Hematologic malignancies: CYT-0851 development plan

In the phase 2 expansion portion of Study CYT-0851-01, we are planning to include cohorts of patients with DLBCL, MCL and MM. In addition, we will have a biomarker selected basket of patients with hematologic malignancies, including FL. CYT-0851 has the potential to be the first DDR-targeting drug to be approved in the United States for hematologic malignancies. If warranted by the phase 1/2 data, and subject to FDA agreement, we intend to initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma.

In the second half of 2021, we also intend to initiate the evaluation of CYT-0851 in combination with standard-of-care cancer drugs for the treatment of hematologic malignancies.

Solid tumors and the current standard of care

Solid tumors are cancers originating from an organ or tissue outside the blood and lymphatic systems. These tumors are further classified, named and ultimately treated based on their tissue of origin, such as breast, ovarian or pancreatic cancer. Solid tumors are responsible for the vast majority of cancers and account for more than 1.5 million new diagnoses in the United States annually. Unlike hematologic malignancies, some solid tumors are identified early through screening procedures or symptomatic presentation prior to spreading throughout the body. In these instances, the cancer can often be removed by surgical excision to ultimately cure the patient’s disease. Outcomes for early-stage disease are highly variable across tumor types, with most early-stage colorectal and breast cancers being cured and almost all pancreatic cancers recurring and metastasizing even despite early intervention. Once solid tumors metastasize, or spread to other sites in the body, the goal of therapy often shifts to long-term control and palliation since cures are typically unattainable. In this incurable setting, the most effective therapies are typically used in combination with the first lines of treatment, and subsequent lines of treatment typically become progressively less effective. The number of available lines of therapy is disease type-specific and generally ranges from as low as one to two lines of therapy in pancreatic cancer and soft tissue sarcoma to more than five lines of therapy in hormone-receptor positive breast cancer. Patients remain on treatment until they have exhausted all therapeutic options, develop symptoms that preclude further treatment or elect to stop further treatment of their cancer.

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Solid tumor market opportunity

According to the American Cancer Society, the 2021 estimated United States annual incidence and mortality of these four types of malignancies included in Study CYT-0851-01 are expected to exceed 125,000 and 66,000, respectively, indicative of the large unmet need.

Tumor Type	2021 estimated incidence		2021 estimated mortality
Pancreatic Cancer		60,000		48,000
Ovarian Cancer		21,000		13,800
Triple Negative Breast Cancer		35,000		NA
Soft Tissue Sarcoma		10,700		4,300
Totals:		126,700		66,100

Solid tumors: CYT-0851 development plan

Several solid tumors express high levels of CDs and have been included in our ongoing Study CYT-0851-01. The phase 2 expansion cohorts will include patients with pancreatic, ovarian, and triple negative breast cancers and soft tissue sarcomas. If warranted by the phase 1/2 data, and subject to FDA agreement, we could initiate a potentially registrational trial in 2022 for the treatment of relapsed and/or refractory lymphoma and/or solid tumors.

In the second half of 2021, we also intend to evaluate CYT-0851 in combination with standard-of-care cancer drugs, which may include chemotherapy or PARP inhibitors, for the treatment of solid tumors.

Mechanism of action

DNA damage is a hallmark of cancer. CYT-0851 works by preventing the repair of the excessive DNA damage present in cancer cells by inhibiting the non-redundant, error-free, dsDNA break repair pathway known as HR. This results in an accumulation of DNA damage sufficient to induce cancer cell death via mitotic catastrophe. Cells overexpressing AID become dependent on HR for their survival because the excessive DNA damage caused by high levels of AID activity requires HR for error-free repair. CYT-0851 was developed to functionally inhibit RAD51-mediated HR and therapeutically exploit such HR dependencies in cancer cells.

CYT-0851 inhibits RAD51-mediated HR and increases DNA damage

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The focal recruitment of the recombinase protein RAD51 to sites of DNA damage within the nuclei of cells undergoing DNA repair is a critical event during HR and is used as a measure of ongoing HR. In the above figure, ongoing HR in the nuclei of an AID-overexpressing lymphoma cell was visualized by staining the RAD51 foci green (panels A and B) and staining the unrepaired DNA red (panels C and D) using gamma H2AX, an endogenous DDR protein that localizes to dsDNA breaks. In these lymphoma cells, ongoing HR was apparent by the abundance of green RAD51 foci (panel A) and productive DNA repair was apparent by the paucity of red gamma H2AX foci (panel C). Upon treatment of the cells with CYT-0851, inhibition of HR-mediated DNA repair was evident by a reduction of green RAD51 foci (panel B versus panel A) and an amplification of red gamma H2AX foci (panel D versus panel C). The bar graphs on the right summarize the effects of CYT-0851 on RAD51 and gamma H2AX foci from approximately 120 lymphoma cells, demonstrating that CYT-0851 significantly inhibits HR-mediated DNA repair.

Preclinical data: monotherapy

CYT-0851 is being developed as a targeted anti-cancer therapy to treat cancers dependent on HR for their survival, irrespective of their tissue of origin. In preclinical studies, CYT-0851 has demonstrated broad-spectrum anti-cancer activity across a large panel of diverse cancer cell lines. In the graph below, each cancer cell line tested is represented by a circle drawn at half the maximal inhibitory concentration, or IC₅₀. CYT-0851 was generally more potent in hematologic malignancies and inhibited the proliferation of a subset of both hematologic- and solid tumor-derived cancer cell lines at IC₅₀s at or below plasma concentrations achieved in patients.

CYT-0851: Efficacious in a broad range of hematologic and solid tumor cell lines

We have observed CYT-0851 to have a favorable tolerability and pharmacokinetic profile across multiple preclinical studies and animal models. In the preclinical in vivo study below, we evaluated once daily (QD), oral (PO) dosing of CYT-0851 in an AID-overexpressing Burkitt’s lymphoma tumor xenograft study. In this study, mice implanted with the lymphoma cells were dosed orally, once daily, over a period of 27 days with vehicle or CYT-0851 at its maximum tolerated dose of 80 mg/kg/day (n=10 mice per group). CYT-0851 was well tolerated and demonstrated complete tumor growth inhibition over the 27-day dosing period. Data points (and error bars) represent mean (+/- standard error) tumor volume of each dosing cohort for each time point.

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CYT-0851: Complete tumor growth inhibition in AID-overexpressing lymphoma model

Beyond hematologic indications, we have tested CYT-0851 in several patient derived xenograft, or PDX, models of solid tumors. In the preclinical study below, we evaluated once daily, oral dosing of CYT-0851 in a pancreatic PDX study. In this study, mice implanted with human-derived pancreatic tumor cells were dosed orally, once daily, over a period of 45 days with vehicle or CYT-0851 at 80 mg/kg/day (n=10 mice per group). CYT-0851 was well tolerated and again demonstrated complete tumor growth inhibition over the 45-day dosing period. Data points (and error bars) represent mean (+/- standard error) tumor volume of each dosing cohort for each time point.

CYT-0851: Complete tumor growth inhibition in patient-derived pancreatic tumor mouse model

Preclinical data: combination therapy

To expand the potential utility of CYT-0851 beyond monotherapy use, we have initiated preclinical studies to explore combinations with a variety of standard-of-care anti-cancer drugs. Analogous to how overexpression of AID induces endogenous DNA damage that creates synthetic lethality with HR inhibition, radiation therapy and certain chemotherapies induce exogenous DNA damage that we believe may also create synthetic lethality with HR inhibition. A documented mechanism of acquired resistance to these therapies is the reliance on DNA repair pathways. By preventing the repair of the DNA damage caused by radiation and chemotherapy, we believe CYT-0851 may improve their effectiveness and delay the development of resistance to therapy.

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Some of the most widely used chemotherapies work by damaging DNA in rapidly dividing cancer cells. Alkylating agents (e.g., platinum-containing drugs and bendamustine), antimetabolites (e.g., gemcitabine) and topoisomerase inhibitors (e.g., topotecan) work through DNA damaging mechanisms that could potentially synergize with CYT-0851 to further enhance their anti-cancer activities. We have begun preclinical testing in cell lines, and we have seen encouraging results with CYT-0851 in combination with chemotherapies that are used to treat many of the same cancers we are exploring in the CYT-0851 monotherapy setting.

CYT-0851: Synergy in combination with DNA damaging chemotherapy

The figure above shows the results from an in vitro experiment performed in a solid tumor cell line using a chemotherapy commonly used in that indication, both with and without the combination of CYT-0851. While the magnitude of the synergy varied across the cell lines studied, in this tumor cell line the addition of 0.75 micromolar CYT-0851 improved the potency of the chemotherapy 40-fold. Based on emerging preclinical combination data such as this, we believe CYT-0851 may be an attractive agent to use in combination with radiation or chemotherapy across multiple cancers.

Beyond radiation and chemotherapy, scientific rationale also exists for combining CYT-0851 with more targeted agents, such as PARP inhibitors. PARP inhibitors work, at least in part, by trapping the PARP protein onto the DNA, ultimately leading to increased DNA damage and dsDNA breaks. By disabling HR-mediated dsDNA break repair, CYT-0851 might be synthetically lethal with PARP inhibitors. We have initiated preclinical experiments to evaluate the potential of combining CYT-0851 with PARP inhibitors in certain tumor types.

A common limitation of many drug combinations is the lack of tolerability. For many of the DDR-targeting agents in development, severe myelosuppression has been particularly limiting to the development of chemotherapy combinations. To date, CYT-0851 has not been associated with any significant myelosuppression as a single agent in patients, nor has it shown adverse pharmacodynamic effects in vitro on human bone marrow cells. We believe this could enable a unique opportunity among DDR-targeted therapies to combine CYT-0851 with either chemotherapies or PARP inhibitors.

Preclinical toxicology studies

Based on the activity observed in cell lines and tumor growth inhibition achieved in animal models, we advanced CYT-0851 toward clinical testing and embarked on IND-enabling toxicology studies in rodents and non-rodents.

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In these toxicology studies we identified the doses and associated systemic exposures that caused toxicity. From these studies we determined the starting dose level in patients and identified potential toxicities that would define the maximum tolerated dose in the phase 1/2 clinical trial. Importantly, in these toxicology studies we observed no significant hematologic toxicity (e.g., myelosuppression) at any doses tested in rodents and non-rodents. If achieved, lack of myelosuppression in patients treated with CYT-0851 would present a significant advantage for CYT-0851 to be used in combination therapy with other cancer drugs that have dose limiting hematologic toxicities.

Biomarker development

Overexpression of CD genes, such as AID and APOBEC3, in cancer cells can cause lethal levels of DNA damage to accumulate. Those cancer cells survive this increased DNA damage by relying on HR to repair the damage and avoid mitotic catastrophe. This increased reliance on HR in the cellular context of CD overexpression presents a therapeutic opportunity for inhibitors of HR, such as CYT-0851.

To verify whether CD gene expression is correlated with sensitivity to CYT-0851 in B cell lymphomas, we compared the level of AID and APOBEC3 gene expression across a panel of 23 Burkitt’s lymphomas (red circles) and DLBCL cell lines (blue squares) that exhibited a range of sensitivities to CYT-0851. We plotted increasing AID/APOBEC3 gene expression from left to right horizontally on the X axis and sensitivity to CYT-0851 on the vertical Y axis with lower IC₅₀ values representing greater sensitivity to CYT-0851. A strong correlation was observed between AID/APOBEC3 gene expression and sensitivity to CYT-0851, consistent with our belief that CD overexpression is synthetically lethal with inhibition of RAD51-mediated HR by CYT-0851.

CYT-0851: Strong correlation between AID/APOBEC3 gene expression and responsiveness

To evaluate whether AID overexpression influenced the sensitivity of cancer cells to CYT-0851, we genetically modified an AID-overexpressing B cell leukemic cell line sensitive to CYT-0851 using CRISPR technology to remove the AID gene. As shown in the figure below, the AID-null cells were approximately 30-fold less sensitive to CYT-0851 (open red squares) than the AID-overexpressing wild-type, or WT, cell line (solid red squares). Importantly, both cell lines were equally sensitive to the topoisomerase inhibitor, topotecan, as reflected by the

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overlapping blue curves. Topotecan is an approved chemotherapeutic agent used as an experimental control in this study to confirm that the AID-null cells are not simply more sensitive to all anti-cancer drugs. This observation further supports our belief that AID overexpression creates synthetic lethality with inhibition of RAD51-mediataed HR that can be therapeutically exploited with CYT-0851.

CYT-0851 preferentially kills AID-Overexpressing over AID-null B cell leukemia cells

For patients with DLBCL, and potentially other non-Hodgkin lymphomas such as Burkitt’s lymphoma, we do not expect patient selection to be necessary, as most patients express high levels of AID and APOBEC3. For patients with other B-cell malignancies and those with solid tumors, if CYT-0851 is approved, we may seek to develop a companion diagnostic to select patients who overexpress CD genes and therefore may be more likely to respond to CYT-0851 therapy.

We have developed a proprietary assay that measures expression levels of AID and several APOBEC3 genes and received an Investigational Device Exemption, or IDE, for this assay. The test can be performed on fresh or archival tumor specimens and is being further evaluated in Study CYT-0851-01. Throughout development, we plan to evaluate the predictive nature of each gene and its respective expression thresholds, which may lead to further refinements in the assay for patient selection.

Beyond CD overexpression, we are exploring additional potential biomarkers that may predict sensitivity to CYT-0851. The observations that not all preclinical tumor models that respond to CYT-0851 express high levels of CD genes suggest there are additional cellular contexts in cancer cells that lead to increased dependency on HR and may be sensitive to CYT-0851. Developing additional biomarkers that identify such cellular contexts and predict sensitivity to CYT-0851 continues to be a focus of our translational biology team. These additional biomarker hypotheses primarily focus on identifying cancer cells dependent on HR and include: (1) evaluating RAD51 expression levels, (2) DNA sequencing of tumor tissue and circulating tumor cell DNA to identify mutations in alternative DNA repair pathways and (3) RNA sequencing to identify predictive gene expression signatures.

CYT-0851 monotherapy clinical trial design (Study CYT-0851-01)

CYT-0851 is being tested in patients in Study CYT-0851-01, a phase 1/2 clinical trial of both hematologic malignancies and solid cancers. We are currently enrolling the phase 1 dose-escalation portion of the study,

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utilizing a standard 3+3 design to establish a single monotherapy dose for all malignancies. Thirty-seven patients have been enrolled in eight dose levels as of March 18, 2021. The primary endpoint is dose-limiting toxicities, or DLTs, to identify the maximally tolerated dose, or MTD. Secondary endpoints are pharmacokinetics, safety, and preliminary anti-tumor activity. Our design also includes pharmacodynamic backfill cohorts that allow us to enroll up to 12 patients in total at any dose level to further characterize the safety, pharmacokinetic, or PK, and pharmacodynamic profiles for dose selection, as well as collect additional tumor biopsies for biomarker development.

Trial design for the phase 1 portion of the trial

When we identify the MTD, we will select a recommended phase 2 dose and proceed into the phase 2 portion of the study. The primary endpoint for this phase is the objective response rate to characterize the anti-tumor activity of CYT-0851 in eight cohorts. The secondary endpoints for this portion include further assessment of the clinical activity in terms of duration of response, progression-free survival, and overall survival, as well as safety and pharmacokinetics.

To assess the primary endpoint, each phase 2 cohort will proceed with a Simon two-stage design. This approach minimizes the number of patients to be enrolled. This design enrolls and evaluates the response in a set number of patients in the first-stage. The proportion of responding patients is assessed and, if sufficient, enrollment into the second stage proceeds to further evaluate the response rate. Our target response rates for each indication are based on historical benchmarks for standard of care. Each cohort will independently guide future development for each disease indication and may include further expansion of the cohort in the current trial, commencement of randomized trials, pursuit of an accelerated approval registration pathway, therapeutic combination strategies or some permutation thereof.

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Trial design for the phase 2 expansion cohorts

Current phase 1/2 trial (Study CYT-0851-01) interim results

As of March 18, 2021, we have enrolled 37 patients across all cohorts and are enrolling at the 300 mg daily dose level. We performed an aggregated analysis for the safety and clinical activity that includes the 23 enrolled patients as of December 8, 2020.

Safety assessment

No patient has reported a DLT or treatment-related serious adverse event, or SAE. Only 24% of patients have reported any treatment-related adverse events, or TRAEs, the majority of which were low-grade (grade 1-2) and manageable.

Treatment related adverse events experienced by patients on trial

Efficacy assessment

As of December 8, 2020, ten patients were considered response-evaluable per protocol (treated with CYT-0851 and had at least one post-baseline disease assessment). Three of these patients (15, 20 and 30 mg twice daily, or BID) received doses considered to be subtherapeutic based upon preclinical modeling. Two of these patients experienced a partial response, or PR, four of these patients had stable disease, or SD, and four of these patients experienced progressive disease, or PD, as their best overall response according to disease specific criteria (RECIST v1.1 or modified Lugano response criteria).

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Response evaluable patients and their best overall change in tumor size and disease specific response

Pharmacokinetic assessment

Preliminary pharmacokinetic analyses of CYT-0851 demonstrated dose proportional systemic exposure. A plasma half-life of approximately three days supported transition from twice daily to once daily administration. Furthermore, the minimum exposure projected to be clinically active, based on preclinical studies, was reached at 45 mg twice daily.

Pharmacodynamic assessment

To assess target engagement, we evaluated the downstream effects (pharmacodynamics) of CYT-0851 by analyzing the accumulation of unrepaired DNA damage/double-strand breaks as measured by gamma H2AX. This was assessed from blood samples containing both circulating tumor cells, or CTCs, and normal blood cells at baseline and on-treatment. Our hypothesis is that if CYT-0851 is inhibiting HR-mediated DNA repair and is specific for tumor cells, then treatment would increase gamma H2AX in CTCs (CK/EpCAM+) while sparing effects in normal blood cells (CD45+). In the three patients with CTCs both at baseline and on treatment, we observed an overall increase in gamma H2AX in two of these patients’ CTCs with no increased DNA damage in normal blood cells (representative image below). In this patient, a 16-fold increase from 59.8 to 939.2 in relative fluorescent intensity of gamma H2AX was observed after treatment.

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Pharmacodynamic effects of CYT-0851 in circulating tumor cells from a patient with pancreatic cancer

CYT-0851 initial patient targeting

Hematologic malignancies

We are initially targeting patients with DLBCL and FL. CYT-0851 has several features that may differentiate it from other drugs on the market and in development for these indications. CYT-0851 is oral and can be dosed as an outpatient treatment. Many of the currently approved therapies require hospitalization or specialized centers for administration, are intravenous, have limited durations of treatment due to the cumulative treatment side effects, and may not be feasibly administered in the community setting. The lack of myelosuppression and the overall safety observed to date in CYT-0851 may allow prolonged dosing strategies and treatment of patients who are elderly or frail or have limited bone marrow and end organ reserve from prior therapies. We have not identified cumulative toxicities in humans treated up to 11 months at current dose levels. CYT-0851 is also potentially combinable with other therapies to both delay the onset of resistance and improve efficacy.

CYT-0851 could be positioned initially as a third or later line of treatment in DLBCL patients whose disease has progressed after two lines of standard therapy, or patients who cannot tolerate standard first- or second-line therapies due to age, frailty or other factors. As most patients with DLBCL have very high levels of CD expression, we do not believe biomarker selection is required.

In FL, CYT-0851 could be positioned initially for CD positive refractory patients as a third or later line of treatment. In preclinical experiments, we have observed a high correlation between CD expression and sensitivity to CYT-0851. Consistent with this preclinical observation, the patient with FL that is experiencing tumor shrinkage is CD positive as measured by our AID/APOBEC3 biomarker assay. If CYT-0851 proves tolerable in FL patients, enabling a long duration of treatment, then we believe the addressable FL market could be substantial.

We plan on including cohorts of MCL and MM patients in the phase 2 expansion portion of Study CYT-0851-01. If results are positive in these cohorts, we anticipate targeting relapsed and/or refractory third line or later MCL

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patients and MM patients previously treated with three prior therapies including a proteasome inhibitor, an immunomodulatory agent, or IMiD, and an anti-CD38 antibody.

Malignancy	Initial treatment opportunity
DLBCL	•   3rd Line+ •   1st/2nd Line+ for elderly/frail patients
FL	•   3rd Line+ •   1st/2nd Line+ for elderly/frail patients
MCL	•   3rd Line+ previously treated with chemotherapy and a Bruton’s tyrosine kinase inhibitor
MM	•   Treated with three prior therapies including a proteosome inhibitor, IMiD and anti-CD38 antibody

Solid tumors

To date in Study CYT-0851-01, we have observed decreases in tumor burden in a pancreatic cancer patient (-19%) and a partial response in a patient with soft tissue sarcoma (-30%). These observations are consistent with our preclinical data indicating that a subset of solid tumor cancer models, including pancreatic and breast cancer PDX models, is sensitive to CYT-0851. Our phase 2 expansion will further evaluate the activity of CYT-0851 in patients with pancreatic, ovarian and triple negative breast cancers, as well as soft tissue sarcomas.

We currently define the initial target patient population in pancreatic cancer to be second and later line treatments. Similarly, the initial target patient populations for triple negative breast cancers are third and later line treatments.

In ovarian cancer, we could initially target CD positive patients that are progressing after platinum-based chemotherapy and PARP inhibitors for patients that are HR deficient. As the majority of patients are receiving both of these agents as part of a first-line regimen, we believe we could target second and later lines as an initial target population.

Soft tissue sarcomas are a heterogeneous collection of tumors from both a cell-of-origin and genetic standpoint. Our analysis of the TCGA database indicates that a high percentage of sarcoma patients have high levels of CD expression. In the phase 1 dose escalation portion of Study CYT-0851-01, we have two sarcoma patients who have been on treatment for at least 136 and 195 days, respectively, without progression, one of whom experienced a partial response by RECIST criteria. Notably, both patients have tolerated the treatment well without any treatment-related adverse events. Based on these observations, and the large unmet need, we believe a path toward accelerated approval of CYT-0851 may be possible. Based on these initial clinical results, we anticipate the initial target population in soft tissue sarcomas will be second or later line treatment.

Tumor type	Initial treatment opportunity
Metastatic or recurrent pancreatic cancer	•  2nd Line+
Advanced ovarian cancer	•  2nd Line+
Metastatic triple negative breast cancer	•  3rd Line+
Soft tissue sarcoma	•  2nd Line+

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CYT-0851 as a combination therapy

Rationale

Cancer treatments are effective at killing the majority of cancer cells, but in doing so create a selective pressure that leads to the outgrowth of resistant clones. One approach that has been successful in addressing this phenomenon is to combine therapies targeting non-redundant pathways. We believe that CYT-0851 provides a rational combination partner for other anti-cancer therapies such as chemotherapy and radiation. These combinations may create synthetic lethality with inhibition of RAD51-meditated HR since one mechanism of resistance is the reliance on DNA repair pathways. Thus, we plan to evaluate the safety and efficacy of CYT-0851 in combination with anti-cancer drugs.

If approved, combination regimens would substantially expand our market opportunities not only into a broader range of indications, but also into earlier lines of therapy where chemotherapy remains a mainstay. These standard-of-care regimens remain highly effective and are otherwise difficult to displace with a monotherapy agent. Based on synergies observed in preclinical experiments combining CYT-0851 with other cancer therapies, we believe CYT-0851 may be safely combined and found to be synergistic with other cancer therapies.

Combination trial plans

CYT-0851 is being developed as a monotherapy in patients who have tumors with high levels of endogenous DNA damage requiring HR for repair and survival. To broaden their potential application, we plan to investigate combinations of CYT-0851 with other standard-of-care cancer therapies that both induce DNA damage (e.g., chemotherapy) and create further reliance on intact HR (e.g., PARP inhibitors). We plan to initiate dosing in a phase 1/2 trial that explores tolerability and preliminary activity of combinations with standard-of-care therapies in the second half of 2021.

CYT-1853: Next generation HR inhibitor program

Program overview

To complement CYT-0851, we are developing CYT-1853 as a next generation inhibitor of RAD51-mediated HR. Importantly, in preclinical models, CYT-1853 is also synthetically lethal in CD-overexpressing cancer cells, is active across a range of cancer cell lines, and exhibits improved potency compared to CYT-0851. We are planning to complete IND-enabling studies in 2021 and to file an IND in 2022.

We believe the following attributes of CYT-1853 allow for the complementary development of both drug candidates:

1. CYT-1853 is more than 10-fold more potent than CYT-0851 in cell-based assays, potentially allowing CYT-1853 to treat tumor types either where CYT-0851 lacks sufficient potency or where resistance to CYT-0851 has developed.

2. CYT-1853 has demonstrated reduced potential for drug-drug interactions, or DDIs, and therefore may broaden its potential for combination therapy.

3. CYT-1853 exhibits more desirable physicochemical properties compared to CYT-0851, such as improved aqueous solubility that enables broader formulation options that may prove beneficial as a development candidate.

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Preclinical data

CYT-1853 is also being developed as a targeted therapy to treat cancers dependent on HR for their survival. Since HR inhibition is synthetically lethal with AID overexpression in B cell malignancies, it was important to evaluate whether AID overexpression led to increased sensitivity to CYT-1853.

To evaluate whether AID overexpression influenced the sensitivity of cancer cells to CYT-1853, we genetically modified an AID-overexpressing B cell leukemic cell line sensitive to CYT-1853 using CRISPR technology to remove the AID gene. As shown in the figure below, the AID-null cells were approximately 100-fold less sensitive to CYT-1853 (open red squares) than the AID-overexpressing WT cell line (solid red squares). Importantly, both cell lines were equally sensitive to the topoisomerase inhibitor, topotecan, as reflected by the overlapping blue curves. This observation further supports our belief that HR inhibitors like CYT-0851 and CYT-1853 are synthetically lethal in CD-overexpressing cancer cells.

CYT-1853 preferentially kills AID-overexpressing compared to AID-null B cell leukemia cells

One of the primary objectives of our next generation program was to identify proprietary compounds at least 10-fold more potent than CYT-0851. As shown below, CYT-1853 was 34-fold more potent than CYT-0851 at inducing cell death in the AID-overexpressing Daudi Burkitt’s lymphoma cell line.

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CYT-1853 is more potent than CYT-0851 at inducing cancer cell death

Beyond Burkitt’s lymphoma, CYT-1853 has demonstrated broad-spectrum anti-cancer activity across a panel of diverse cancer cell lines. As shown below, CYT-1853 is active across multiple hematologic and solid tumor cell lines and is generally more than 10-fold more potent than CYT-0851 at inhibiting cancer cell proliferation, as measured by the IC₅₀. The dots represent individual cancer cell lines across multiple tumor types as indicated by the colored legend. The black diagonal dotted line represents equipotency between CYT-1853 and CYT-0851 so cell lines that lie below the diagonal were more sensitive to CYT-1853. The observation that most of the cell lines were more sensitive to CYT-1853 than CYT-0851 supports the possibility that CYT-1853 may be able to treat tumor types where CYT-0851 lacks sufficient efficacy. Specifically, cell lines that fall in the shaded box may represent cancers that, due to their increased sensitivity, might be more effectively treated with CYT-1853 than CYT-0851.

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CYT-1853 exhibits potent and broad activity across multiple cancer cell lines

We also evaluated CYT-1853 in in vivo tumor models. In the preclinical study below, we evaluated twice daily oral dosing of CYT-1853 in an AID-overexpressing Daudi Burkitt’s lymphoma tumor xenograft model. In this study, mice implanted with tumor cells were dosed twice daily over a period of 17 days with vehicle or CYT-1853 at tolerated doses of 10, 25 or 50 mg/kg BID (n=6 mice per group). CYT-1853 was well-tolerated and demonstrated complete tumor growth inhibition at 50 mg/kg BID over the 17-day dosing period. Data points (and error bars) represent mean (+/- standard error) tumor volume of each dosing cohort for each time point.

CYT-1853: Significant tumor growth inhibition in AID-overexpressing lymphoma model

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Our discovery approach and pipeline

We are using our expertise in DDR biology and a disciplined approach to select targets for other novel, differentiated drug discovery and development programs. Our approach includes:

• systematically prioritizing DDR targets based on our deep understanding of DDR biology, coupled with the mining of mutational information collected on diseased tissues and the analysis of results from both internal and external CRISPR-based genetic, chemical and cellular phenotypic synthetic lethality screens;

• elucidating synthetic lethality dependencies of our drug targets and using that information to molecularly define patient populations most likely to benefit from our therapies as a monotherapy, and assuring tumor selectivity that limits side effects and allows our drugs to be used in combination with other standard anti-cancer therapies;

• developing potent, highly selective, well tolerated, small molecule therapies against these targets and evaluating them in biomarker-selected in vitro and in vivo model systems; and

• expeditiously progressing lead candidates through preclinical studies and into focused clinical trials in defined patient populations using a biomarker-guided approach.

Our core capabilities in discovery biology focusing on DNA damage repair have enabled us to move rapidly and efficiently from drug discovery to clinical development. We have the management team with the successful global registration experience to potentially advance our drug candidates to registration. In only three years, we progressed CYT-0851 from discovery to clinical proof of concept. In 2021, we intend to define the optimal development plan for potentially achieving accelerated approval of CYT-0851 initially as monotherapy in late lines of treatment for certain lymphomas and/or solid tumors. In addition, we may broaden the target patient population in both hematologic malignancies and solid tumors and move to earlier lines of treatment, either alone and/or in combination with standard-of-care therapies.

Furthermore, we have identified an undisclosed second target, a protein in one of the DNA repair pathways other than HR, as well as subsets of cancers that depend on this protein for their survival. We have identified a potential biomarker for use in candidate development and, ultimately, patient selection. Importantly, expression of this protein is prognostic, meaning patients whose cancer cells overexpress this protein generally have shorter survival compared to patients whose cancer cells do not. We are in the discovery stage of this program, and we anticipate reaching the drug candidate nomination stage and initiating IND-enabling studies in 2022.

In addition to advancing this second target, we continue to evaluate other DDR drug targets internally. We will continue to invest in our capacity to identify novel DDR targets and advance additional drug development programs.

Competition

While we believe that our technology, drug development expertise and deep understanding of DDR biology provide us with certain competitive advantages, we face competition from many pharmaceutical and biotechnology companies, as well as academic institutions that are involved in the discovery, development, and commercialization of oncology therapeutics. To our knowledge, we are the only company with a drug candidate in clinical development targeting RAD51-mediated HR, and we believe that we could potentially have the first approval of a DDR targeting therapy in hematologic malignancies.

Many other companies are advancing oncology therapeutics that target DNA repair, including AbbVie, Artios Pharma, AstraZeneca, BeiGene, Breakpoint Therapeutics, Bristol Myers Squibb, Clovis Oncology, EMD Serono, Foghorn Therapeutics, Genentech, GlaxoSmithKline, IDEAYA Biosciences, Merck & Co, Pfizer, Repare

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Therapeutics and Tango Therapeutics. In addition, academic and other non-profit organizations have early-stage ongoing drug discovery efforts that target DNA repair, such as Cancer Research UK, University of Chicago, and Dana Farber Cancer Institute. In addition, to gain market acceptance for our drug candidates, if they are approved for commercial sale, we will face competition from numerous companies that are developing novel cancer therapeutics using a variety of modalities other than targeting DNA repair.

Our success will be based upon our ability to advance CYT-0851 and our portfolio of DDR drug candidates through clinical development to regulatory approval and successful commercialization. We believe our therapeutics have the potential to be more tolerable and more effective than competing products in our target indications both as a monotherapy and in combination with standard-of-care chemotherapy. Our competitive position will also depend on our ability to attract and retain qualified personnel relative to peer companies and in light of the highly competitive market for talent in the biopharmaceutical industry, to obtain and maintain patent protection or otherwise to develop proprietary products and protect and enforce our intellectual property, and to secure sufficient capital to support our research and development efforts in a way that allows us achieve our preclinical and clinical development goals relative to our competitors.

We could see a reduction or elimination in our commercial opportunity if our competitors develop and commercialize drugs that are safer, more effective, have fewer or less severe side effects, are more convenient to administer, or are less expensive than our drug candidates. Our competitors also may obtain FDA or other regulatory approval for their drugs more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. The key competitive factors affecting the success of all of our drug candidates, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

Intellectual property

We strive to obtain, maintain, protect, enforce and enhance the proprietary technology, inventions and improvements that we believe are commercially important to the development of our business, including by seeking, maintaining, enforcing and defending patent rights, whether developed internally or licensed from third parties. We also rely on trade secrets, know-how, and continuing technological innovation to develop, strengthen and maintain our proprietary position in our field.

Our future commercial success depends, in part, on our ability to: obtain and maintain patent and other intellectual property and proprietary protection for commercially important technology, inventions and know-how related to our business; defend and enforce our intellectual property and proprietary rights, in particular our patents rights; preserve the confidentiality of our trade secrets; operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and other intellectual property and proprietary rights of third parties; and prevent others from infringing, misappropriating or otherwise violating our intellectual property and proprietary rights. Our ability to stop unauthorized third parties from making, using, selling, offering to sell or importing our products may depend on the extent to which we have rights under valid and enforceable patents, trade secrets or other intellectual property or proprietary rights that cover these activities.

As of March 23, 2021, we owned two issued U.S. patents, six pending U.S. non-provisional patent applications, one pending U.S. provisional patent application, 28 pending foreign patent applications, and four pending Patent Cooperation Treaty, or PCT, applications.

A subset of our patent portfolio relates to CYT-0851, and includes patents and patent applications directed to CYT-0851 and certain methods of use. As of March 23, 2021, we owned two issued U.S. patents, four pending

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U.S. non-provisional patent applications, one pending U.S. provisional patent application, 21 pending foreign patent applications, and three pending PCT applications related to CYT-0851. As of March 23, 2021, we owned one pending U.S. non-provisional patent application, one pending foreign patent application and one pending PCT application related to CYT-1853. We do not currently own or in-license any issued patents related to CYT-1853. The foregoing patents and patent applications will, if issued, have statutory expiration dates between 2038 and 2041, excluding any patent term adjustments or patent term extensions that may be available.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file patent applications, including the U.S., the patent term is 20 years from the earliest date of filing a non-provisional patent application. In addition, in the U.S., in certain instances, a patent term can be extended by a patent term adjustment to recapture a portion of the U.S. Patent and Trademark Office, or the USPTO, review period in issuing the patent and/or by patent term extension to account for a portion of the term effectively lost as a result of the FDA regulatory review period, and a patent term may be shortened if a patent is terminally disclaimed over an earlier filed patent. As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our drug candidates will depend on our success in obtaining effective patent claims and enforcing those claims if granted. However, our owned and licensed pending patent applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents. We also cannot predict the breadth of claims that may be allowed or enforced in our owned or licensed patents or whether such claims, if issued, will cover our drug candidates, provide sufficient protection from competitors or otherwise provide any competitive advantage. Any issued patents that we may receive or in-license in the future may be challenged, invalidated, narrowed, held unenforceable, infringed or circumvented. In addition, because of the extensive time required for clinical development and regulatory review of a drug candidate we may develop, it is possible that, before any of our drug candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby limiting the protection such patent would afford the respective product and any competitive advantage such patent may provide.

We cannot be certain of the priority of inventions covered by our owned or licensed patents and pending patent applications, in part because patent applications in the United States and certain other jurisdictions are maintained in secrecy for 18 months or potentially even longer, and because publication of discoveries in the scientific or patent literature often lags behind actual discoveries and patent application filings. Accordingly, we may not have been the first to invent the subject matter disclosed in some of our patents and patent applications or the first to file patent applications covering such subject matter.

In addition to patent protection, we rely upon unpatented trade secrets and confidential know-how and continuing technological innovation to develop and maintain our competitive position. However, trade secrets and confidential know-how are difficult to protect. We seek to protect our proprietary information, in part, using confidentiality agreements with any collaborators, scientific advisors, employees and consultants and invention assignment agreements with our employees. We also have agreements requiring assignment of inventions with consultants, scientific advisors and collaborators who are involved in the creation of our technology. These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, grant us ownership of technologies that are developed through our relationship with the counterparty. However, these agreements may not provide meaningful protection, and we cannot guarantee that we have executed such agreements with all applicable counterparties. These agreements may also be breached, and we may not have an adequate remedy for any such breach. In addition, our trade secrets and/or confidential know-how may become known or be independently developed by a third party, or misused by any collaborator to whom we disclose such information. Despite any measures taken to protect our intellectual property, unauthorized parties may attempt to copy aspects of our products or to obtain or use

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information that we regard as proprietary. Although we take steps to protect our proprietary information, third parties may independently develop the same or similar proprietary information or may otherwise gain access to our proprietary information. To the extent that our collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. As a result, we may be unable to meaningfully protect our trade secrets and proprietary information.

See “Risk Factors—Risks Related to our Intellectual Property” for a more comprehensive description of risks related to our intellectual property.

Manufacturing

We currently rely and expect to continue relying on contract development and manufacturing organizations, or CDMOs, to manufacture our drug substances and drug products for preclinical and clinical testing and for future commercial manufacturing of our products. We require the CDMOs manufacturing our drug substances and drug products for clinical testing to comply with current good manufacturing practices, or cGMP, requirements. We have assembled a team of experienced employees and consultants to provide the required technical, quality, and regulatory oversight over our CDMOs. The development of our analytical methods to control and analyze our products is maintain at a phase appropriate level corresponding to the clinical development.

Our drug substances are small molecules and our CDMOs manufacture them by synthetic processes from available starting materials. We expect to continue the development of the manufacturing processes of our drug substances at CDMOs and to produce them in a cost-effective manner and meeting all regulatory requirements.

Commercialization

We currently employ no staff dedicated to commercialization activities. If we receive regulatory approval for CYT-0851, we anticipate building an internal staff to undertake commercial activities in the United States such as reimbursement, marketing, and sales, as well as medical affairs and pharmacovigilance. For our first approved product, we may partner with one or more biopharmaceutical companies to access commercialization capabilities for support in the United States and for all activities in ex-U.S. global markets where we receive regulatory approvals. If we have multiple approved products over time, we anticipate internalizing all commercial activities for the United States and potentially other major markets.

Government regulation

The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, recordkeeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs. We, along with our vendors, contract research organizations and contract manufacturers, will be required to navigate the various preclinical, clinical, manufacturing and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our drug candidates. The process of obtaining regulatory approvals of drugs and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

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In the United States, where we are initially focusing our drug development, the FDA regulates drug products under the Federal Food, Drug, and Cosmetic Act, or FD&C Act, as amended, its implementing regulations and other laws. If we fail to comply with applicable FDA or other requirements at any time with respect to product development, clinical testing, approval or any other legal requirements relating to product manufacture, processing, handling, storage, quality control, safety, marketing, advertising, promotion, packaging, labeling, export, import, distribution, or sale, we may become subject to administrative or judicial sanctions or other legal consequences. These sanctions or consequences could include, among other things, the FDA’s refusal to approve pending applications, issuance of clinical holds for ongoing studies, suspension or revocation of approved applications, warning or untitled letters, product withdrawals or recalls, product seizures, relabeling or repackaging, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution.

The process required by the FDA before our drug candidates are approved as drugs for therapeutic indications and may be marketed in the United States generally involves the following:

• completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with good laboratory practice, or GLP, requirements;

• completion of the manufacture, under current good manufacturing practices, or cGMP, conditions, of the drug substance and drug product that the sponsor intends to use in human clinical trials along with required analytical and stability testing;

• submission to the FDA of an investigational new drug application, or IND, which must become effective before clinical trials may begin;

• approval by an institutional review board, or IRB, or independent ethics committee at each clinical trial site before each trial may be initiated;

• performance of adequate and well-controlled clinical trials in accordance with applicable IND regulations, good clinical practice, or GCP, requirements and other clinical trial-related regulations to establish the safety and efficacy of the investigational product for each proposed indication;

• submission to the FDA of a new drug application, or NDA;

• a determination by the FDA within 60 days of its receipt of an NDA, to accept the filing for review;

• satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the drug will be produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

• potentially, satisfactory completion of FDA audit of the clinical trial sites that generated the data in support of the NDA;

• payment of user fees for FDA review of the NDA; and

• FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the drug in the United States.

Preclinical studies and clinical trials for drugs

Before testing any drug in humans, the drug candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluations of drug chemistry, formulation and stability, as well as in vitro and animal studies to assess safety and in some cases to establish the rationale for therapeutic use. The conduct of

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preclinical studies is subject to federal and state regulation, including GLP requirements for safety/toxicology studies. The results of the preclinical studies, together with manufacturing information and analytical data, must be submitted to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before clinical trials may begin. Some long-term preclinical testing may continue after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial, including concerns that human research subjects will be exposed to unreasonable health risks, and imposes a full or partial clinical hold. FDA must notify the sponsor of the grounds for the hold and any identified deficiencies must be resolved before the clinical trial can begin. Submission of an IND may result in the FDA not allowing clinical trials to commence or not allowing clinical trials to commence on the terms originally specified in the IND. A clinical hold can also be imposed once a trial has already begun, thereby halting the trial until the deficiencies articulated by FDA are corrected.

The clinical stage of development involves the administration of the drug candidate to healthy volunteers or patients under the supervision of qualified investigators, who generally are physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirements that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND. Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable compared to the anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may recommend to the sponsor to halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as a lack of observed efficacy. There also are requirements governing the reporting of ongoing clinical trials and completed clinical trials to public registries. For example, information about clinical trials, including results for clinical trials other than Phase 1 investigations, must be submitted within specific timeframes for publication on www.ClinicalTrials.gov, a clinical trials database maintained by the National Institutes of Health.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. If a foreign clinical trial is not conducted under an IND, FDA will nevertheless accept the results of the study in support of an NDA if the study was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials to evaluate therapeutic indications to support NDAs for marketing approval are typically conducted in three sequential phases, which may overlap.

• Phase 1—Phase 1 clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition. These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism, distribution, and excretion of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.

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• Phase 2—Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the drug’s potential efficacy, to determine the optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks. It is common to combine Phase 1 and Phase 2 studies in oncology drug development.

• Phase 3—Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval and physician labeling.

Post-approval trials, sometimes referred to as Phase 4 clinical trials or post-marketing studies, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to generate additional safety data regarding use of the product in a clinical setting. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of NDA approval.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA. Written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines the information qualifies for reporting for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human volunteers and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must also notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than seven calendar days after the sponsor’s initial receipt of the information.

During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points. These points may be prior to submission of an IND, at the end of Phase 2, and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug candidate and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration over its shelf life.

U.S. marketing approval for drugs

Assuming successful completion of the required clinical testing, the results of the preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA package requesting approval to market the product for one or more indications. An NDA is a request for approval to market a new drug for one or more specified indications and must contain proof of the drug’s safety and efficacy for the requested indications. The marketing application is required to include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company-sponsored

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clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA must approve an NDA before a drug may be marketed in the United States.

The FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA for filing. The FDA must make a decision on accepting an NDA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA. Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the NDA. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective for the indications sought and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity. Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA targets ten months, from the filing date, in which to complete its initial review of a new molecular entity NDA and respond to the applicant, and six months from the filing date of a new molecular entity NDA for priority review. The FDA does not always meet its PDUFA goal dates for standard or priority NDAs, and the review process is often extended by FDA requests for additional information or clarification.

Further, under PDUFA, as amended, each NDA must be accompanied by a substantial user fee. The FDA adjusts the PDUFA user fees on an annual basis. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The FDA also may require submission of a Risk Evaluation and Mitigation Strategy, or REMS, if it believes that a risk evaluation and mitigation strategy is necessary to ensure that the benefits of the drug outweigh its risks. A REMS can include use of risk evaluation and mitigation strategies like medication guides, physician communication plans, assessment plans, and/or elements to assure safe use, such as restricted distribution methods, patient registries, or other risk-minimization tools.

The FDA may refer an application for a novel drug to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, which reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and are adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter. A complete response letter generally contains a statement of specific conditions that must be met in order to secure final approval of the NDA and may require additional clinical or preclinical testing in order for the FDA to reconsider the application. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

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Even if the FDA approves a product, depending on the specific risk(s) to be addressed it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Orphan drug designation and exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making the product available in the United States for the disease or condition will be recovered from sales of the product. Orphan designation must be requested before submitting an NDA. Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process, though companies developing orphan products are eligible for certain incentives, including tax credits for qualified clinical testing and waiver of application fees.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to a seven-year period of marketing exclusivity during which the FDA may not approve any other applications to market the same therapeutic agent for the same indication, except in limited circumstances, such as a subsequent product’s showing of clinical superiority over the product with orphan exclusivity or where the original applicant cannot produce sufficient quantities of product. Competitors, however, may receive approval of different therapeutic agents for the indication for which the orphan product has exclusivity or obtain approval for the same therapeutic agent for a different indication than that for which the orphan product has exclusivity. Orphan product exclusivity could block the approval of one of our products for seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do, unless we are able to demonstrate that our product is clinically superior. If an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity. Further, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Expedited development and review programs for drugs

The FDA maintains several programs intended to facilitate and expedite development and review of new drugs to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions. These programs include Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval, and the purpose of these programs is to either expedite the development or review of important new drugs to get them to patients more quickly than standard FDA review timelines typically permit.

A new drug is eligible for Fast Track designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition. Fast Track designation provides increased opportunities for sponsor interactions with the FDA during preclinical and

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clinical development, in addition to the potential for rolling review once a marketing application is filed. Rolling review means that the agency may review portions of the marketing application before the sponsor submits the complete application. In addition, a new drug may be eligible for Breakthrough Therapy designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Breakthrough Therapy designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient drug development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy designation, may also be eligible for additional FDA programs intended to expedite the review and approval process, including Priority Review designation and Accelerated Approval. A product is eligible for Priority Review, once an NDA is submitted, if the drug that is the subject of the marketing application has the potential to provide a significant improvement in safety or effectiveness in the treatment, diagnosis or prevention of a serious disease or condition. Under priority review, the FDA’s goal date to take action on the marketing application is six months compared to ten months for a standard review. Products are eligible for Accelerated Approval if they can be shown to have an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Accelerated Approval is usually contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the product’s clinical benefit. The FDA may withdraw approval of a drug or an indication approved under Accelerated Approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product. In addition, the FDA generally requires, as a condition for Accelerated Approval, that all advertising and promotional materials intended for dissemination or publication within 120 days of marketing approval be submitted to the agency for review during the pre-approval review period. After the 120-day period has passed, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or the time period for FDA review or approval may not be shortened. Furthermore, Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval, though they may expedite the development or review process.

Pediatric information and pediatric exclusivity

The Pediatric Research Equity Act, or PREA, requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, as amended, certain NDAs and NDA supplements must contain data that can be used to assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. The FD&C Act requires that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of

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administration submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

A drug can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing marketing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

U.S. post-approval requirements for drugs

Drugs manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, reporting of adverse experiences with the product, complying with promotion and advertising requirements, which include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry-sponsored scientific and educational activities. Although physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including investigation by federal and state authorities. Prescription drug promotional materials must be submitted to the FDA in conjunction with their first use or first publication. Further, if there are any modifications to the drug, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new NDA or NDA supplement, which may require the generation of additional data or the conduct of additional preclinical studies and clinical trials.

The FDA may impose a number of post-approval requirements as a condition of approval of an NDA. For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements. Failure to comply with statutory and regulatory requirements may subject a manufacturer to legal or regulatory action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution. There is also a continuing, annual prescription drug product program user fee.

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Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS. Other potential consequences include, among other things:

• restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

• the issuance of safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product;

• fines, warning letters or holds on post-approval clinical trials;

• refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of product approvals;

• product seizure or detention, or refusal to permit the import or export of products;

• injunctions or the imposition of civil or criminal penalties; and

• consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; or mandated modification of promotional materials and labeling and issuance of corrective information.

Patent term restoration and extension

Depending upon the timing, duration and specifics of FDA approval of our drug candidates, some of a sponsor’s U.S. patents may be eligible for limited patent term extension, or PTE, under the Hatch-Waxman Amendments. As compensation for patent term lost during product development and the FDA regulatory review process, the Hatch-Waxman Amendments permit a patent restoration term, which is limited to a maximum of five years, or less if the extended patent term would exceed 14 years after the date of the regulatory approval of the product. The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of an NDA plus the time between the submission date of an NDA, less any time the sponsor did not act with due diligence during the period and the approval of that application less any time the sponsor did not act with due diligence during the period. Only one patent applicable to an approved drug or drug product is eligible for the extension, only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended, and the application for the extension must be submitted prior to the expiration of the patent. Moreover, a given patent may only extended once based on a single product. The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug. In the future, we may intend to apply for restoration of a patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant NDA. However, we may not receive an extension if we fail to exercise due diligence during the testing phase or regulatory review process, fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements. Moreover, the length of the extension could be less than we request. There can be no assurance that we will benefit from any PTE or favorable adjustment to the term of any of our patents. For more information regarding the risks related to our intellectual property, see “Risk Factors—Risks Related to Our Intellectual Property.”

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Marketing exclusivity

Market exclusivity provisions authorized under the FD&C Act can delay the submission or the approval of certain marketing applications. The FD&C Act provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application, or ANDA, or an NDA submitted under Section 505(b)(2), or 505(b)(2) NDA, submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The FD&C Act alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to any preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

In addition, pediatric exclusivity and orphan drug exclusivity, as described above, may offer a six-month or seven-year period of exclusivity, respectively, except in certain circumstances.

Regulation of companion diagnostics

Companion diagnostics are diagnostic tests designed to identify patients who may be most likely to benefit from a particular therapeutic product, identify patients likely to be at increased risk for serious side effects as a result of treatment with a particular therapeutic product, or monitor response to treatment with a particular therapeutic product. On August 6, 2014, the FDA issued a final guidance document addressing the development and approval process for “In Vitro Companion Diagnostic Devices.” According to the guidance document, for novel therapeutic products that depend on the use of a diagnostic test and where the diagnostic device could be essential for the safe and effective use of the corresponding therapeutic product, the companion diagnostic device should be developed and approved or cleared contemporaneously with the therapeutic, although the FDA recognizes that there may be cases when contemporaneous development may not be possible. However, in cases where a drug cannot be used safely or effectively without the companion diagnostic, the FDA’s guidance indicates it will generally not approve the drug without the approval or clearance of the diagnostic device. The FDA also issued a draft guidance in July 2016 setting forth the principles for co-development of an in vitro companion diagnostic device with a therapeutic product. The draft guidance describes principles to guide the development and contemporaneous marketing authorization for the therapeutic product and its corresponding in vitro companion diagnostic.

Companion diagnostics are regulated as medical devices by the FDA. In the United States, the FD&C Act, and its implementing regulations, and other federal and state statutes and regulations govern, among other things, medical device design and development, preclinical and clinical testing, premarket clearance or approval,

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registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance. Unless an exemption or FDA exercise of enforcement discretion applies, diagnostic tests generally require marketing clearance or approval from the FDA prior to commercialization. The two primary types of FDA marketing authorization applicable to a medical device are clearance of a premarket notification, or 510(k), and approval of a premarket approval application, or PMA.

To obtain 510(k) clearance for a medical device, or for certain modifications to devices that have received 510(k) clearance, a manufacturer must submit a premarket notification demonstrating that the proposed device is substantially equivalent to a previously cleared 510(k) device or to a pre-amendment device that was in commercial distribution before May 28, 1976, or a predicate device, for which the FDA has not yet called for the submission of a PMA. In making a determination that the device is substantially equivalent to a predicate device, the FDA compares the proposed device to the predicate device and assesses whether the subject device is comparable to the predicate device with respect to intended use, technology, design and other features which could affect safety and effectiveness. If the FDA determines that the subject device is substantially equivalent to the predicate device, the subject device may be cleared for marketing. The 510(k) premarket notification pathway generally takes from three to twelve months from the date the application is completed, but can take significantly longer.

A PMA must be supported by valid scientific evidence, which typically requires extensive data, including technical, preclinical, clinical and manufacturing data, to demonstrate to the FDA’s satisfaction the safety and effectiveness of the device. For diagnostic tests, a PMA typically includes data regarding analytical and clinical validation studies. As part of its review of the PMA, the FDA will conduct a pre-approval inspection of the manufacturing facility or facilities to ensure compliance with the quality system regulation, or QSR, which requires manufacturers to follow design, testing, control, documentation and other quality assurance procedures. The FDA’s review of an initial PMA is required by statute to take between six to ten months, although the process typically takes longer, and may require several years to complete. If the FDA evaluations of both the PMA and the manufacturing facilities are favorable, the FDA will either issue an approval letter or an approvable letter, which usually contains a number of conditions that must be met in order to secure the final approval of the PMA. If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny the approval of the PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable. Once granted, PMA approval may be withdrawn by the FDA if compliance with post-approval requirements, conditions of approval or other regulatory standards is not maintained or problems are identified following initial marketing.

Once cleared or approved, the companion diagnostic device must adhere to post-marketing requirements including the requirements of the FDA’s QSR, adverse event reporting, recalls and corrections along with product marketing requirements and limitations. Like drug makers, companion diagnostic makers are subject to unannounced FDA inspections at any time during which the FDA will conduct an audit of the product(s) and the company’s facilities for compliance with its authorities.

Other regulatory matters

Manufacturing, sales, promotion and other activities of drug candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the United States in addition to the FDA, which may include the Centers for Medicare & Medicaid Services, or CMS, other divisions of the U.S. Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.

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Other healthcare laws

Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of any products for which we obtain marketing approval. Our business operations and any current or future arrangements with third-party payors, healthcare providers and physicians may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we develop, market, sell and distribute any drugs for which we obtain marketing approval. In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician transparency, and patient data privacy and security laws and regulations, including but not limited to those described below.

• The federal Anti-Kickback Statute prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid; a person or entity need not have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it in order to have committed a violation. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs. In addition, the government may assert that a claim that includes items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act.

• The federal civil and criminal false claims laws, including the civil False Claims Act, or FCA, prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false, fictitious or fraudulent; knowingly making, using, or causing to be made or used, a false statement or record material to a false or fraudulent claim or obligation to pay or transmit money or property to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery. When an entity is determined to have violated the federal civil False Claims Act, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs.

• The federal civil monetary penalties laws impose civil fines for, among other things, the offering or transfer or remuneration to a Medicare or state healthcare program beneficiary, if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state health care program, unless an exception applies.

• The Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for knowingly and willfully executing a scheme, or attempting to execute a scheme, to defraud any healthcare benefit program, including private payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, or falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services.

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose, among other things, specified requirements

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on covered entities and their business associates relating to the privacy and security of individually identifiable health information including mandatory contractual terms and required implementation of technical safeguards of such information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates in some cases, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

• The Physician Payments Sunshine Act, which imposes annual reporting requirements for certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, for certain payments and “transfers of value” provided to physicians (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Effective January 1, 2022, these reporting obligations will extend to include transfers of value made in the previous year to certain non-physician providers such as physician assistants and nurse practitioners.

• Federal consumer protection and unfair competition laws broadly regulate marketplace activities and activities that potentially harm consumers.

• Analogous state and foreign laws and regulations may be broader in scope than the provisions described above and may apply regardless of payor. Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and relevant federal government compliance guidance; require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers; restrict marketing practices or require disclosure of marketing expenditures and pricing information. State and foreign laws may govern the privacy and security of health information in some circumstances. These data privacy and security laws may differ from each other in significant ways and often are not pre-empted by HIPAA, which may complicate compliance efforts.

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations. Federal and state enforcement bodies have recently increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other related governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, disgorgement, exclusion from government funded healthcare programs, such as Medicare and Medicaid, reputational harm, additional oversight and reporting obligations if we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found not to be in compliance with applicable laws, they may be subject to similar actions, penalties and sanctions. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert a company’s attention from its business.

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Coverage and reimbursement by third-party payors

In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Thus, even if a drug candidate is approved, sales of the product will depend, in part, on the extent to which third-party payors, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage, and establish adequate reimbursement levels for, the product. In the United States, the Medicare and Medicaid programs are increasingly used as models for how private and other governmental payors develop their coverage and reimbursement policies for drugs. No uniform policy of coverage and reimbursement for drug products exists, however, among third-party payors. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical necessity, reviewing the cost-effectiveness of medical products and services and imposing controls to manage costs. Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the approved products for a particular indication.

In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, which will require additional expenditure above and beyond the costs required to obtain FDA or other comparable regulatory approvals. Additionally, companies may also need to provide discounts to purchasers, private health plans or government healthcare programs. Nonetheless, drug candidates may not be considered medically necessary or cost effective. A decision by a third-party payor not to cover a product could reduce physician utilization once the product is approved and have a material adverse effect on sales, our operations and financial condition. Additionally, a third-party payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage and reimbursement for the product, and the level of coverage and reimbursement can differ significantly from payor to payor.

The containment of healthcare costs has become a priority of federal, state and foreign governments, and the prices of products have been a focus in this effort. Governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any approved products. Coverage policies and third-party payor reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which a company or its collaborators receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Current and future healthcare reform legislation

In the United States and some foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes regarding the healthcare system directed at broadening the availability of healthcare, improving the quality of healthcare, and containing or lowering the cost of healthcare. For example, in March 2010, the United States Congress enacted the Affordable Care Act, which, among other things, includes changes to the coverage and payment for products under government health care programs.

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Since its enactment, there have been numerous judicial, administrative, executive, and legislative challenges to certain aspects of the Affordable Care Act, and we expect there will be additional challenges and amendments to the Affordable Care Act in the future. For example, various portions of the Affordable Care Act are currently facing legal and constitutional challenges in the Fifth Circuit Court of Appeals and the United States Supreme Court. Additionally, the current administration has issued various Executive Orders which eliminated cost sharing subsidies and various provisions that would impose a fiscal burden on states or a cost, fee, tax, penalty or regulatory burden on individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices, and Congress has introduced several pieces of legislation aimed at significantly revising or repealing the Affordable Care Act. It is unclear whether the Affordable Care Act will be overturned, repealed, replaced, or further amended. We cannot predict what effect further changes to the Affordable Care Act would have on our business.

Other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted. In August 2011, the Budget Control Act of 2011, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2030, with a temporary suspension from May 1, 2020 through December 31, 2020, unless additional Congressional action is taken. In addition, in January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, including bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their commercial products, which has resulted in several Congressional inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products. Although a number of these measures may require additional authorization to become effective, Congress and the current administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.

On July 24, 2020, President Trump announced a number of executive orders related to prescription drug pricing that attempt to implement several of the Administration’s proposals, including a policy that would tie Medicare Part B drug prices to international drug prices; one that directs HHS to finalize the Canadian drug importation proposed rule previously issued by HHS and makes other changes allowing for personal importation of drugs from Canada; and one that directs HHS to finalize the rulemaking process on modifying the anti-kickback law safe harbors for plans, pharmacies, and pharmaceutical benefit managers after HHS confirms that the action is not projected to increase federal spending, Medicare beneficiary premiums, or patients’ total out-of-pocket costs. The probability of success of these newly announced policies and their impact on the U.S. prescription drug marketplace is unknown. There are likely to be political and legal challenges associated with implementing these reforms as they are currently envisioned.

Individual states in the United States have also increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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Outside the United States, ensuring coverage and adequate payment for a product also involves challenges. Pricing of prescription pharmaceuticals is subject to government control in many countries. Pricing negotiations with government authorities can extend well beyond the receipt of regulatory approval for a product and may require a clinical trial that compares the cost-effectiveness of a product to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in commercialization. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries.

Other U.S. environmental, health and safety laws and regulations

We may be subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and may also produce hazardous waste products. Even if we contract with third parties for the disposal of these materials and waste products, we cannot completely eliminate the risk of contamination or injury resulting from these materials. In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

We maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees, but this insurance may not provide adequate coverage against potential liabilities. However, we do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. Current or future environmental laws and regulations may impair our research, development or production efforts. In addition, failure to comply with these laws and regulations may result in substantial fines, penalties or other sanctions.

Government regulation of drugs outside of the United States

To market any product outside of the United States, we would need to comply with numerous and varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of drug products. Whether or not we obtain FDA approval for a product, we would need to obtain the necessary approvals by the comparable foreign regulatory authorities before we can commence clinical trials or marketing of the product in those countries or jurisdictions. The approval process ultimately varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others. As in the United States, post-approval regulatory requirements, such as those regarding product manufacture, marketing, or distribution would apply to any product that is approved outside the United States.

Facilities

Our corporate headquarters is located at 128 Spring St, Building A, Suite 510, Lexington, MA 02421, where we lease and occupy approximately 14,636 square feet of office and laboratory space. The current term of our 128 Spring St. lease expires in 2023.

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To meet the future needs of our business, we may lease additional or alternate space, and we believe suitable additional or alternative space will be available in the future on commercially reasonable terms.

Employees

As of December 31, 2020, we had 22 full-time employees. Thirteen of our employees have M.D. or Ph.D. degrees. Within our workforce, 15 employees are engaged in research and development and seven are engaged in business development, finance, legal, and general management and administration. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.

Legal proceedings

From time to time, we may become involved in litigation or other legal proceedings. We are not currently a party to any litigation or legal proceedings that, in the opinion of our management, are probable to have a material adverse effect on our business. Regardless of outcome, litigation can have an adverse impact on our business, financial condition, results of operations and prospects because of defense and settlement costs, diversion of management resources and other factors.

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Management

Executive officers and directors

Our executive officers and directors, and their ages and positions as of February 28, 2021, are as set forth below:

Name	Age		Position(s)
Executive Officers
Markus Renschler, M.D.		59	President, Chief Executive Officer, Director
Andrew Gengos		56	Chief Business Officer
Paul Secrist, Ph.D.		55	Chief Scientific Officer
David Gaiero		42	Vice President, Finance
Non-Employee Directors
Racquel Bracken		38	Director
Jean George, M.B.A		62	Director
Karen Hong, Ph.D.		49	Director
Susan Molineaux, Ph.D.		67	Director
Janwillem Naesens, M.Sc., M.B.A		38	Director
Timothy Romberger		48	Director
Joseph S. Zakrzewski		58	Director

Executive officers

Markus Renschler, M.D. has served as a member of our board of directors since May 2016, and as President & Chief Executive Officer since January 2018. Previously, Dr. Renschler was an executive at Celgene from 2008 to 2017, serving as Senior VP and Chief Medical Officer of Celgene Cellular Therapeutics, Senior VP and Global Head of Hematology Oncology Medical Affairs, VP of Business Development and VP of Clinical Research & Development. Prior to that, from 2007 to 2008, Dr. Renschler was VP of Clinical Development at Pharmion Corporation. Prior to that from 1996 to 2007, Dr. Renschler served in different clinical development roles at Pharmacyclics, last as Senior VP, Oncology Clinical Development. Dr. Renschler has over 25 years’ experience in building successful biopharmaceutical companies and in cancer research from basic laboratory research to drug approval and drug launches. Dr. Renschler had responsibility for successful global registrations and launches in breast cancer, non-small cell lung cancer and pancreatic cancer as well as the medical strategy for drug launches in hematologic malignancies and solid tumors for drugs such as REVLIMID^® (lenalidomide), POMALYST^® (pomalidomide), ABRAXANE^® (nab-paclitaxel), and VIDAZA^® (azacytidine). Dr. Renschler was a post-doctoral fellow with Dr. Ronald Levy at Stanford University. Dr. Renschler is a board-certified medical oncologist with an MD from Stanford University and BA from Princeton University. Dr. Renschler was an Adjunct Clinical Associate Professor of Medicine (Oncology) at Stanford University until 2015, where he was teaching and treating patients in the lymphoma program. Over his career, Dr. Renschler has authored or co-authored over 40 scientific papers and has been named as an inventor on numerous issued and pending patents. We believe Dr. Renschler is qualified to serve on our board of directors due to his extensive experience in the

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biotechnology industry, cancer drug discovery and development, corporate governance, business development and executive leadership.

Andrew Gengos has served as our Chief Business Officer since February 2020. Prior to joining Cyteir, Mr. Gengos served as Chief Business Officer and Chief Financial Officer of AOBiome Therapeutics from January 2019 to December 2019. Prior to that, from October 2017 to December 2018, Mr. Gengos served as Chief Operating Officer and Head of Corporate Development at Synlogic Inc. Before joining Synlogic, Mr. Gengos served as Chief Executive Officer, President, and Director of ImmunoCellular Therapeutics from December 2012 to December 2016. Prior to that, Mr. Gengos served as Vice President of Strategy and Corporate Development at Amgen from 2002 to 2010. Prior to Amgen, Mr. Gengos was Senior Engagement Manager at McKinsey & Company from 1991 to 1998, focusing in their healthcare practice. Mr. Gengos received his B.S. in Chemical Engineering from the Massachusetts Institute of Technology and an M.B.A. from the UCLA Anderson School of Management.

Paul Secrist, Ph.D. has served as our Chief Scientific Officer since June 2020. Prior to joining Cyteir, Dr. Secrist was the Senior Vice President of Discovery Research at Lifemine Therapeutics from January 2018 until June 2020. Prior to that, Dr. Secrist served as Sr. Principal Scientist and Director at AstraZeneca Pharmaceuticals from September 2011 to December 2017. Prior to that, Dr. Secrist has served in various scientific leadership roles at drug discovery and development companies including OSI Pharmaceuticals, Aton Pharma, and Merck & Company since beginning his pharmaceutical and biotechnology career in 1996. In these organizations, Dr. Secrist led multiple preclinical drug discovery, drug development and translational biology programs, focusing primarily in oncology. Dr. Secrist received a bachelor’s degree in Biology from Wartburg College and a Ph.D. in Pharmacology from Mayo Graduate School. He received his post-doctoral training at National Jewish Hospital in Denver, CO.

David Gaiero has served as our Vice President of Finance since December 2020. Prior to joining Cyteir, Mr. Gaiero served in various roles at Wave Life Sciences from 2017 to 2020, most recently serving as Interim Chief Financial Officer and prior to that, serving as Vice President and Corporate Controller. Prior to joining Wave, from 2015 to 2017, Mr. Gaiero served as Vice President and Corporate Controller of OvaScience, Inc. Prior to that, Mr. Gaiero held various positions of increasing responsibility and scope in finance and accounting at iRobot Corporation. Mr. Gaiero began his career in public accounting at PricewaterhouseCoopers LLP. Mr. Gaiero received a B.B.A. in Accounting from the University of Massachusetts, Amherst, and is a Certified Public Accountant in Massachusetts.

Non-employee directors

Racquel Bracken has served as a member of our board of directors since 2018. Ms. Bracken currently serves as a Partner at Venrock, where she has worked since May 2016, and focuses on pharmaceutical and biotech investments. Prior to Venrock, Ms. Bracken was a founding early employee of Clovis Oncology, a biopharmaceutical company focused on acquiring, developing and commercializing targeted small molecule therapies in combination with companion diagnostics. Earlier in her career, Ms. Bracken was on the investment team at Domain Associates, where she focused on early-stage healthcare investing. Prior to joining Domain, Ms. Bracken was a consultant at Easton Associates, a management consultancy dedicated to the medical industry. Ms. Bracken is also a co-founder and member of the board of directors of Federation Bio, where she has served since January 2019, and Prothelia Therapeutics, where she has served since May 2020. Ms. Bracken received an A.B. in molecular and cellular biology from Harvard University and is a member of the Kaufman Fellows. We believe Ms. Bracken is qualified to serve on our board of directors due to her knowledge and experience in the venture capital and biopharmaceutical industries.

Jean George, M.B.A. has served as a member of our board of directors since 2018. Ms. George is currently a General Partner of Lightstone Ventures, where she focuses on biopharmaceutical and medical device

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investments, which position she has held since April 2013. Ms. George is also a General Partner of Advanced Technology Ventures, which position she has held since February 2002. Ms. George has been featured on the Forbes Midas List and was previously a member of the Scientific Advisory Board for the Massachusetts Life Sciences Center. Ms. George has been in the biopharmaceutical industry for over 20 years, including 10 years with Genzyme Corporation, where she held a variety of operation roles in marketing, product development, and business development, including Vice President of Global Sales and Marketing. Ms. George was also Vice President and Founder of Genzyme’s Tissue Repair Division. Ms. George currently serves on the board of directors of Calithera Biosciences, Inc. since 2010, Gemini Therapeutics since 2016, and a number of private companies. Ms. George previously served on the board of directors of Acceleron Pharma, Inc. from 2005 to April 2020, Zeltiq Aesthetics from October 2013 to June 2015 and Catabasis Pharmaceuticals, Inc. from 2010 to June 2019. Ms. George received a B.S. in Biology from the University of Maine and an M.B.A. from Simmons College Graduate School of Management. We believe Ms. George is qualified to serve on our board of directors due to her knowledge and experience in the venture capital and biopharmaceutical industries.

Karen Hong, Ph.D. has served as a member of our board of directors since October 2019. Since April 2019, Dr. Hong has been employed as a partner at Novo Ventures (US), Inc., which provides consulting services to Novo Holdings A/S, an investment firm focused on life sciences and finance. Prior to Novo, Dr. Hong was a Partner at Takeda Ventures, Inc from May 2017 to April 2019, and, before that, held roles including Associate, Principal and Partner at ProQuest Investments from June 2001 to March 2016. Prior to joining ProQuest, Dr. Hong led numerous research projects in the area of mammalian cancer genetics and genomics in the laboratory of Dr. Eric Lander at the Whitehead Institute for Biomedical Research. Dr. Hong served on the board of Agile Therapeutics from May 2006 to July 2016. Dr. Hong has also served on the board of directors of Obsidian Therapeutics, Palleon Pharmaceuticals and Clarus Therapeutics. In addition, she was an observer on the board of directors of BioRexis Pharmaceutical Corp., Gloucester Pharmaceuticals and LEAD Therapeutics, among others. Dr. Hong received a B.A. in Molecular Biology and B.S. in Chemistry from the University of California at Berkeley, where she graduated with honors and as a member of Phi Beta Kappa, and a Ph.D. in Molecular Biology from the Massachusetts Institute of Technology. We believe Dr. Hong is qualified to serve on our board of directors due to her substantial experience in life science investing and biomedical research as well as her experience serving on the board of directors of multiple public and private biopharmaceutical companies.

Susan Molineaux, Ph.D. has served as a member of our board of directors since 2020. Dr. Molineaux has also served as a member of the board of directors of Theravance Biopharma Inc. since 2015 and Geron Corporation since 2012. Dr. Molineaux also has been Chief Executive Officer, President and a member of the board of directors of Calithera Biosciences, Inc., a biotechnology company developing oncology therapeutics, since co-founding the company in June 2010. Prior to starting Calithera, Dr. Molineaux was a co-founder of Proteolix and served as Chief Scientific Officer for two years before becoming Proteolix’s President and Chief Executive Officer. Proteolix was acquired by Onyx Pharmaceuticals in November 2009. Prior to co-founding Proteolix, Dr. Molineaux was Vice President of Biology at Rigel Pharmaceuticals from 2000 to 2003. Before that, she was Vice President of Biology at Praelux, and from 1994 to 1999, Dr. Molineaux served as Vice President of Drug Development at Praecis Pharmaceuticals. From 1989 to 1994, Dr. Molineaux was a scientist in the immunology group at Merck. Dr. Molineaux received a B.S. in Biology from Smith College and a Ph.D. in Molecular Biology from Johns Hopkins University. Dr. Molineaux completed a postdoctoral fellowship at Columbia University. We believe Dr. Molineaux is qualified to serve on our board of directors due to her extensive experience as an executive officer at biopharmaceutical companies, as well as her scientific background.

Janwillem Naesens, M.Sc., M.B.A. has served as a member of our board of directors since 2019. Mr. Naesens currently serves as Managing Director of Droia Ventures, a specialist investor in early-stage drug development companies, which position he has held since September 2013. Prior to joining Droia in 2013, Mr. Naesens was an

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Investment Manager at Waterland Private Equity, a European investment group providing growth capital to small and mid-sized companies. Mr. Naesens started his career at McKinsey & Company in New York, working as a strategy consultant in life sciences and finance. Mr. Naesens currently serves on the board of directors of Frontier Medicines, Ambagon Therapeutics, Ananke Therapeutics, Highlight Therapeutics, Octimet Oncology and Black Belt Therapeutics. Mr. Naesens is also a board observer at PACT Pharmaceuticals and Accent Therapeutics, and was formerly a board member of Tusk Therapeutics. Mr. Naesens holds a M.Sc. in Engineering from the University of Leuven and an M.B.A. from INSEAD, Fontainebleau. We believe Mr. Naesens is qualified to serve on our board of directors due to his knowledge and experience in the venture capital and oncology drug development industries.

Timothy Romberger our co-founder, has served as a member of our board of directors since 2015. Mr. Romberger served as our acting Chief Executive and Head of Business Development from 2012 to the fall of 2015. Mr. Romberger played an instrumental role in the engagement of Celgene as an early strategic partner and the closing of both the Series A and Series B investment rounds. Mr. Romberger is currently Managing Director of TRC Advisory, LLC, a business strategy consulting firm that he founded in July 2014. Before founding Cyteir and TRC, Mr. Romberger served as Managing Director at Marakon Associates, a global strategy consultancy. Mr. Romberger is an experienced business strategist and entrepreneur with more than 25 years of experience advising CEOs and their leadership teams in the areas of strategy, commercial effectiveness and organizational development. Mr. Romberger holds a degree in Economics and Corporate Finance from the University of Pennsylvania—Wharton School of Business. We believe Mr. Romberger is qualified to serve on our board of directors due to his expertise and experience as our co-founder and his extensive experience as a business strategist.

Joseph S. Zakrzewski has served as a member of our board of directors since 2018 and chairman since 2020. Mr. Zakrzewski has also served as a member of the board of directors of Amarin Corporation since 2010, Acceleron Pharma Inc. since 2011 and Sangamo Therapeutics, Inc. since June 2017. Mr. Zakrzewski also served as chairman of the board of directors of Onxeo S.A. from 2015 to 2019. From 2008 through 2017, Mr. Zakrzewski served as a member of the board of directors of Insulet Corporation. From 2010 through 2013, Mr. Zakrzewski served as Chairman and Chief Executive Officer of Amarin. From 2007 to 2010, Mr. Zakrzewski served as President and Chief Executive Officer of Xcellerex. From 2005 to 2007, Mr. Zakrzewski served as the Chief Operating Officer of Reliant Pharmaceuticals. From 1988 to 2004, Mr. Zakrzewski served in a variety of positions at Eli Lilly and Company including as Senior Vice President, Corporate Business Development from 2003 through 2004. In addition, Mr. Zakrzewski served as a Venture Partner with OrbiMed in 2010 and 2011. He also currently serves and has previously served on the board of directors of a number of privately held companies. Mr. Zakrzewski received a BS in Chemical Engineering and an MS in Biochemical Engineering from Drexel University as well as an MBA in Finance from Indiana University. We believe that Mr. Zakrzewski’s substantial experience as an executive officer of other pharmaceutical companies, as well as Mr. Zakrzewski’s service on boards of directors of other pharmaceutical companies qualify him to serve as a member of our Board of Directors.

Board composition and election of directors

Classified board of directors

In accordance with our amended and restated certificate of incorporation, which will be in effect upon the closing of this offering, our board of directors will be divided into three classes of directors. At each annual meeting of stockholders, a class of directors will be elected for a three-year term to succeed the class whose terms are then expiring, to serve from the time of election and qualification until the third annual meeting

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following their election or until their earlier death, resignation or removal. Upon the closing of this offering, our directors will be divided among the three classes as follows:

The Class I directors will be                , and their terms will expire at our first annual meeting of stockholders following this offering.

The Class II directors will be                 , and their terms will expire at our second annual meeting of stockholders following this offering.

The Class III directors will be                , and their terms will expire at our third annual meeting of stockholders following this offering.

Our amended and restated certificate of incorporation will provide that the authorized number of directors may be changed only by resolution of our board of directors. Any additional directorships resulting from an increase in the number of directors will be distributed among the three classes so that, as nearly as possible, each class will consist of one-third of the directors. The division of our board of directors into three classes with staggered three-year terms may delay or prevent a change of our management or a change in control. See the section of this prospectus captioned “Description of Capital Stock—Anti-takeover Effects of Our Certificate of Incorporation and Our By-laws” for a discussion of these and other anti-takeover provisions found in our amended and restated certificate of incorporation and amended and restated by-laws, which will become effective immediately prior to the closing of this offering.

Director independence

Under the rules of the                 , independent directors must comprise a majority of a listed company’s board of directors within one year of the completion of its initial public offering. In addition, the                 rules of the require that, subject to specified exceptions, each member of a listed company’s audit and compensation committees be independent and that director nominees be selected or recommended for the board’s selection by independent directors constituting a majority of the independent directors or by a nominating and corporate governance committee comprised solely of independent directors. Under the rules of the                 , a director will only qualify as “independent” if, in the opinion of that company’s board of directors, that person does not have a relationship that would interfere with the exercise of independent judgment in carrying out the responsibilities of a director and that such person is “independent” as defined under                 and the Exchange Act rules.

Audit committee members must also satisfy the independence criteria set forth in Rule 10A-3 under the Exchange Act. In order to be considered independent for purposes of Rule 10A-3, a member of an audit committee of a listed company may not, other than in his or her capacity as a member of the audit committee, the board of directors or any other board committee: (1) accept, directly or indirectly, any consulting, advisory or other compensatory fee from the listed company or any of its subsidiaries or (2) be an affiliated person of the listed company or any of its subsidiaries.

Based upon information requested from and provided by each director concerning his or her background, employment and affiliations, including family relationships, our board of directors has determined that each of our directors, with the exception of Dr. Renschler, is an “independent director” as defined under applicable rules of the                 , including, in the case of all the members of our audit committee, the independence criteria set forth in Rule 10A-3 under the Exchange Act, and in the case of all the members of our compensation committee, the independence criteria set forth in Rule 10C-1 under the Exchange Act and are “non-employee directors” as defined in Section 16b-3 of the Exchange Act. In making such determination, our board of directors considered the relationships that each such non-employee director has with our Company and all other facts

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and circumstances that our board of directors deemed relevant in determining his or her independence, including the beneficial ownership of our capital stock by each non-employee director. Dr. Renschler is not an independent director under these rules because he is our President and Chief Executive Officer.

Board committees

Our board of directors has established an audit committee, a compensation committee and a nominating and corporate governance committee, each of which will operate pursuant to a charter adopted by our board of directors and which will be effective prior to the consummation of this offering. The board of directors may also establish other committees from time to time to assist us and the board of directors in their duties. Upon the effectiveness of the registration statement of which this prospectus forms a part, the composition and functioning of all of our committees will comply with all applicable requirements of the Sarbanes-Oxley Act, the                 and the Exchange Act. Upon our listing on the                , each committee’s charter will be available on the corporate governance section of our website at www.cyteir.com. Information contained on our website is not incorporated by reference into this prospectus, and you should not consider information contained on our website to be part of this prospectus or in deciding whether to purchase shares of our common stock.

Audit committee

The audit committee’s responsibilities upon completion of this offering will include:

• appointing, approving the compensation of, and evaluating the qualifications, performance and independence of our independent registered public accounting firm;

• overseeing the work of our independent registered public accounting firm, including through the receipt and consideration of reports from such firm, and pre-approving all audit and permitted non-audit services to be performed by our independent registered public accounting firm;

• reviewing and discussing with management and our independent registered public accounting firm our annual and quarterly financial statements and related disclosures, including earnings releases;

• reviewing and discussing with management and our independent registered public accounting firm any material issues regarding accounting principles and financial statement presentations;

• coordinating our board of directors’ oversight of our internal control over financial reporting, disclosure controls and procedures, code of business conduct and ethics, procedures for complaints and legal and regulatory matters;

• discussing our risk management policies with management;

• establishing policies regarding hiring employees from our independent registered public accounting firm and procedures for the receipt and retention of accounting related complaints and concerns;

• meeting independently with our independent registered public accounting firm and management;

• reviewing and approving any related person transactions;

• overseeing our guidelines and policies governing risk assessment and risk management;

• overseeing the integrity of our information technology systems, process and data;

• preparing the audit committee report required by SEC rules;

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• reviewing and assessing, at least annually, the adequacy of the audit committee’s charter; and

• performing, at least annually, an evaluation of the performance of the audit committee.

All audit services and all non-audit services, other than de minimis non-audit services, to be provided to us by our independent registered public accounting firm must be approved in advance by our audit committee.

The members of our audit committee are                .                chairs the audit committee. Our board of directors has determined that each member of our audit committee has sufficient knowledge in financial and auditing matters to serve on the audit committee. Our board of directors has also determined that                 is an “audit committee financial expert,” as defined under Item 407 of Regulation S-K.

Compensation committee

Our compensation committee’s responsibilities upon completion of this offering will include:

• assisting our board of directors in developing and reviewing potential candidates for executive positions;

• reviewing our overall compensation strategy, including base salary, incentive compensation and equity-based grants;

• reviewing and approving corporate goals and objectives relevant to compensation of our chief executive officer and our other executive officers;

• recommending to our board of directors the compensation of our chief executive officer and other executive officers;

• reviewing and making recommendations to the board of directors with respect to director compensation;

• overseeing and administering our cash and equity incentive plans;

• reviewing, considering and selecting, to the extent determined to be advisable, a peer group of appropriate companies for purposing of benchmarking and analysis of compensation for our executive officers and directors;

• reviewing and approving all employment contract and other compensation, severance and change-in- control arrangements for our executive officers;

• recommending to our board of directors any stock ownership guidelines for our executive officers and non-employee directors;

• retaining, appointing or obtaining advice of a compensation consultant, legal counsel or other advisor, and determining the compensation and independence of such consultant or advisor;

• preparing, if required, the compensation committee report on executive compensation for inclusion in our annual proxy statement in accordance with the proxy rules;

• monitoring our compliance with the requirements of Sarbanes-Oxley relating to loans to directors and officers;

• overseeing our compliance with applicable SEC rules regarding shareholder approval of certain executive compensation matters;

• reviewing the risks associated with our compensation policies and practices;

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• reviewing and assessing, at least annually, the adequacy of the compensation committee’s charter; and

• performing, on an annual basis, an evaluation of the performance of the compensation committee.

The members of our compensation committee are                .                chairs the compensation committee. Prior to establishing a compensation committee, our board of directors made decisions relating to the compensation of our executive officers.

Nominating and governance committee

Our nominating and corporate governance committee’s responsibilities upon completion of this offering will include:

• identifying individuals qualified to become members of our board of directors consistent with criteria approved by the board and receiving nominations for such qualified individuals;

• recommending to our board of directors the persons to be nominated for election as directors and to each committee of the board;

• establishing a policy under which our shareholders may recommend a candidate to the nominating and corporate governance committee for consideration for nomination as a director;

• reviewing and recommending committee slates on an annual basis;

• recommending to our board of directors qualified candidates to fill vacancies on our board of directors;

• developing and recommending to our board of directors a set of corporate governance principals applicable to us and reviewing the principles on at least an annual basis;

• reviewing and making recommendations to our board with respect to our board leadership structure and board committee structure;

• reviewing, in concert with our board of directors, our policies with respect to significant issues of corporate public responsibility;

• making recommendations to our board of directors processes for annual evaluations of the performance of our board of directors, our chief executive officer and committees of our board of directors;

• overseeing the process for annual evaluations of our board of directors, chief executive officer and committees of our board of directors and certifying that performance of our chief executive officer and other members of executive management is being properly evaluated;

• considering and reporting to our board of directors any questions of possible conflicts of interest of members of our board of directors;

• providing new director orientation and continuing education for existing directors on a periodic basis;

• overseeing the maintenance and presentation to our board of directors of management’s plans for succession to senior management positions in the Company;

• reviewing and assessing, at least annually, the adequacy of the nominating and corporate governance committee’s charter; and

• performing, on an annual basis, an evaluation of the performance of the nominating and corporate governance committee.

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The members of our nominating and corporate governance committee are                .                chairs the nominating and corporate governance committee. Our board of directors has determined that each member of the nominating and corporate governance committee satisfies the independence standards of the applicable rules of the                 .

Our board of directors may establish other committees from time to time.

Role of the board in risk oversight

Our board of directors has an active role, as a whole and also at the committee level, in overseeing the management of our risks. Our board of directors is responsible for general oversight of risks and regular review of information regarding our risks, including liquidity risks and operational risks. The compensation committee is responsible for overseeing the management of risks relating to our executive compensation plans and arrangements. The audit committee is responsible for overseeing the management of risks relating to accounting matters and financial reporting. The nominating and governance committee is responsible for overseeing the management of risks associated with the independence of our board of directors and potential conflicts of interest. Although each committee is responsible for evaluating certain risks and overseeing the management of such risks, the entire board of directors is regularly informed through discussions from committee members about such risks. Our board of directors believes its administration of its risk oversight function has not negatively affected our board of directors’ leadership structure.

Code of business conduct and ethics

Prior to the closing of this offering, we will adopt a written code of business conduct and ethics that applies to our directors, officers and employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions, which will become effective upon the effectiveness of the registration statement of which this prospectus forms a part. Following this offering, a current copy of the code will be posted on the investor section of our website. In addition, we intend to post on our website all disclosures that are required by law or listing rules concerning any amendments to, or waivers from, any provision of the code.

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Executive and director compensation

The following discussion and analysis of compensation arrangements should be read with the compensation tables and related disclosures set forth below. This discussion contains forward looking statements that are based on our current plans and expectations regarding future compensation programs. The actual compensation programs that we adopt may differ materially from the programs summarized in this discussion.

Introduction

This section provides an overview of the compensation awarded to, earned by or paid to our principal executive officer and our next two most highly compensated executive officers listed below in respect of their service to us for the fiscal year ended December 31, 2020. We refer to these individuals as our named executive officers. Our named executive officers are:

• Markus Renschler, M.D., our President and Chief Executive Officer;

• Andrew Gengos, our Chief Business Officer; and

• Paul Secrist, Ph.D., our Chief Scientific Officer.

The compensation committee of our board of directors is responsible for determining the compensation of our executive officers. Our Chief Executive Officer made recommendations to the compensation committee about the compensation of his direct reports, including Mr. Gengos and Dr. Secrist, in respect of fiscal year 2020.

Summary compensation table

The following table sets forth the compensation awarded to, earned by or paid to our named executive officers in respect of their service to us for the fiscal year ended December 31, 2020:

Name and principal position	Year		Salary ($)		Bonus ($)(1)		Option awards ($)(2)		Nonequity incentive plan compensation ($)(3)		Total ($)
Markus Renschler, M.D.		2020		450,000		—		106,116		180,000		736,116
President and Chief Executive Officer
Andrew Gengos(4)		2020		299,674		25,000		246,205		111,832		682,711
Chief Business Officer
Paul Secrist, Ph.D.(5)		2020		172,769		25,000		248,104		67,456		513,329
Chief Scientific Officer

(1) The amounts reported in this column reflect a $25,000 signing bonus paid to each of Mr. Gengos and Dr. Secrist in connection with the commencement of his employment with us.

(2) The amounts reported in this column represent the aggregate grant date fair value of stock options granted to each of our named executive officers during fiscal 2020 determined in accordance with ASC Topic 718. The underlying valuation assumptions for these stock option awards are discussed in Note 9 to our consolidated financial statements included elsewhere in this prospectus.

(3) The amounts reported in this column represent annual bonuses earned by our named executive officers in respect of fiscal 2020 based on the attainment of corporate performance goals as described below under “Annual bonuses”.

(4) Mr. Gengos commenced employment with us on February 24, 2020.

(5) Dr. Secrist commenced employment with us on June 15, 2020.

Narrative disclosure to summary compensation table

Annual base salary

The letter agreement with each named executive officer, described below, establishes an annual base salary for the officer, which was determined at the time that the named executive officer commenced employment with us and is subject to periodic review.

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Annual bonuses

With respect to fiscal year 2020, each of Drs. Renschler and Secrist and Mr. Gengos was eligible to receive an annual bonus, with the target amount of such bonus for each named executive officer set forth in his letter agreement with us, described below. For fiscal year 2020, the target bonus amount, expressed as a percentage of annual base salary, for Dr. Renschler was 40% and for each of Mr. Gengos and Dr. Secrist was 35%. Annual bonuses for fiscal year 2020 for our named executive officers were based on the attainment of corporate objectives relating to building the leadership team, driving key research and development and pipeline objectives and managing cash preservation, as determined by the compensation committee. For 2020, each of Dr. Renschler, Mr. Gengos and Dr. Secrist received 100% of his target bonus, pro-rated as applicable for any partial year of service, or $180,000, $111,832 and $67,456, respectively.

Agreements with our named executive officers

Drs. Renschler and Secrist and Mr. Gengos are each party to an employment agreement with us that sets forth the terms and conditions of his respective employment. The material terms of the agreements are described below. The terms “cause,” “good reason” and “change in control” referred to below are defined in the respective named executive officer’s agreement.

Dr. Renschler.    We entered into an employment agreement with Dr. Renschler, effective November 10, 2017, which has since been amended. Dr. Renschler’s employment agreement, as amended, provides for an initial annual base salary of $400,000 per year, which has subsequently been increased, and a target bonus equal to 35% of his annual base salary, which has subsequently been increased. The actual amount of the bonus is payable based upon the achievement of quantitative and qualitative performance objectives established by our board of directors. Dr. Renschler’s employment agreement also provides that, for so long as Dr. Renschler serves as our President and Chief Executive Officer, he will also serve as a member of our board of directors.

Dr. Renschler’s employment agreement contains a perpetual non-disparagement covenant. Dr. Renschler is also party to a Non-Competition Agreement pursuant to which he has agreed not to compete with us during his employment and for one year following the termination of his employment other than due to a layoff or a termination by us without cause. He is also party to a Nondisclosure, Inventions and Nonsolicitation Agreement under which he has agreed to a perpetual confidentiality covenant and an assignment of intellectual property covenant, and has agreed not to solicit our business partners and employees during his employment and for one year following the termination of his employment for any reason.

Mr. Gengos.    We entered into an employment agreement with Mr. Gengos, effective February 24, 2020, that provides for an annual base salary of $375,000 per year, and a target bonus equal to 35% of his annual base salary. The actual amount of the bonus is payable based on achievement of performance goals established by our board of directors. The employment agreement provides for the grant of an option to purchase 940,000 shares of our common stock, described below under “Equity compensation,” and for a one-time signing bonus of $25,000, which is repayable by Mr. Gengos if his employment is terminated by us for cause or by him without good reason, in either case before February 24, 2022.

Under his employment agreement, Mr. Gengos has agreed not to compete with us during his employment and for one year following the termination of his employment other than due to a layoff or a termination by us without cause, and not to solicit our business partners, employees and independent contractors during his employment and for one year following the termination of his employment for any reason. In addition, he has agreed to a perpetual confidentiality covenant, a perpetual non-disparagement covenant and an assignment of intellectual property covenant. Mr. Gengos is also party to a Nondisclosure, Inventions and Nonsolicitation Agreement under which he has agreed to a perpetual confidentiality covenant and an assignment of intellectual

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property covenant, and has agreed not to solicit our business partners and employees during his employment and for one year following the termination of his employment for any reason.

Dr. Secrist.    We entered into an employment agreement with Dr. Secrist, effective June 15, 2020, that provides for an annual base salary of $350,000 per year and a target bonus equal to 35% of his annual base salary. The actual amount of the bonus is payable based on achievement of performance goals established by our board of directors. The employment agreement provides for the grant of an option to purchase 940,000 shares of our common stock, described below under “Equity compensation,” and for a one-time signing bonus of $25,000, which is repayable by Dr. Secrist if his employment is terminated by us for cause or by him without good reason, in either case before June 15, 2022.

Under his employment agreement, Dr. Secrist has agreed not to compete with us during his employment and for one year following the termination of his employment other than due to a layoff or a termination by us without cause, and not to solicit our business partners, employees and independent contractors during his employment and for one year following the termination of his employment for any reason. In addition, he has agreed to a perpetual confidentiality covenant, a perpetual non-disparagement covenant and an assignment of intellectual property covenant. Dr. Secrist is also party to a Nondisclosure, Inventions and Nonsolicitation Agreement under which he has agreed to a perpetual confidentiality covenant and an assignment of intellectual property covenant, and has agreed not to solicit our business partners and employees during his employment and for one year following the termination of his employment for any reason.

Severance upon termination of employment; change in control

Dr. Renschler.    Under his employment agreement, as amended, if Dr. Renschler’s employment is terminated by us without cause or by him for good reason, he will be entitled to continued payment of his base salary for a period of six months following such termination. Dr. Renschler and our board of directors have agreed to negotiate in good faith within six months following an initial public offering whether an increase to his severance entitlement is appropriate.

If Dr. Renschler’s employment is terminated by us without cause or by him for good reason, in either case within 24 months following a change in control, Dr. Renschler will be entitled to (i) continued payment of his base salary for a period of 12 months following such termination, (ii) accelerated vesting of all outstanding stock options and other equity-based awards and (iii) extended exercisability of each outstanding stock option through the original term of the stock option.

Mr. Gengos.    Under his employment agreement, if Mr. Gengos’s employment is terminated by us without cause or by him for good reason, he will be entitled to (i) continued payment of his base salary for six months and (ii) subject to his timely election of COBRA coverage, payment of a monthly amount equal to the monthly health premiums paid by us on behalf of Mr. Gengos and his eligible dependents prior to such termination for six months (or, if earlier, until he ceases to be eligible for COBRA coverage or obtains health coverage from another employer).

If Mr. Gengos’s employment is terminated by us without cause or by him for good reason, in either case within 12 months following a change in control, then in addition to the severance entitlements described above, Mr. Gengos will be entitled to accelerated vesting of all outstanding stock options and other equity-based awards.

Dr. Secrist.    Under his employment agreement, if Dr. Secrist’s employment is terminated by us without cause or by Dr. Secrist for good reason, he will be entitled to continued payment of his base salary for a period of six months following such termination.

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If Dr. Secrist’s employment is terminated by us without cause or by him for good reason, in either case within 12 months following a change in control, then in addition to the severance entitlement described above, Dr. Secrist will be entitled to accelerated vesting of all outstanding stock options and other equity-based awards.

Severance Subject to Conditions.    Our obligation to provide an executive with severance payments and other benefits under the executive’s letter agreement is conditioned on the executive signing a release of claims in favor of us and complying with the restrictive covenants applicable to him.

Equity compensation

Each of our named executive officers received stock option grants in fiscal year 2020 under the Cyteir Therapeutics, Inc. 2012 Stock Incentive Plan, or the 2012 Plan.

On February 25, 2020, Dr. Renschler was granted an option to purchase 415,000 shares of our common stock, which vests in 48 equal monthly installments commencing on January 1, 2020, generally subject to Dr. Renschler’s continued employment with us through the applicable vesting date.

On March 24, 2020, Mr. Gengos was granted an option to purchase 752,000 shares of our common stock, which vests as to 25% of the shares underlying the award on February 24, 2021 and as to the remaining shares underlying the award in 36 equal monthly installments thereafter, generally subject to Mr. Gengos’s continued employment with us through the applicable vesting date. On March 24, 2020, Mr. Gengos was also granted an option to purchase 188,000 shares of our common stock, which vests as to 75% of the shares underlying the award on February 24, 2023 and as to the remaining shares underlying the award in 12 equal monthly installments thereafter, generally subject to Mr. Gengos’s continued employment with us through the applicable vesting date.

On July 22, 2020, Dr. Secrist was granted an option to purchase 752,000 shares of our common stock, which vests as to 25% of the shares underlying the award on June 15, 2021 and as to the remaining shares underlying the award in 36 equal monthly installments thereafter, generally subject to Dr. Secrist’s continued employment with us through the applicable vesting date. On July 22, 2020, Dr. Secrist was also granted an option to purchase 188,000 shares of our common stock, which vests as to 75% of the shares underlying the award on June 15, 2023 and as to the remaining shares underlying the award in 12 equal monthly installments thereafter, generally subject to Dr. Secrist’s continued employment with us through the applicable vesting date.

In December 2020, our board of directors approved an amendment to all outstanding stock option award agreements to allow for early exercise of unvested stock options in exchange for shares of restricted stock subject to the same vesting schedule as the underlying stock options. Each of Dr. Renschler and Mr. Gengos elected to early exercise a portion of the stock options granted to him and, as of December 31, 2020, held 853,750 shares of restricted stock and 250,666 shares of restricted stock, respectively.

Employee and retirement benefits

We currently provide broad-based health and welfare benefits that are available to all of our employees, including our named executive officers, including health, life and AD&D, disability, vision and dental insurance. In addition, we maintain a 401(k) retirement plan for our full-time employees. The 401(k) plan also permits us to make discretionary employer contributions. We did not make any discretionary employer contributions to the 401(k) plan in 2020. Other than the 401(k) plan, we do not provide any qualified or non-qualified retirement or deferred compensation benefits to our employees, including our named executive officers.

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Outstanding awards at fiscal year-end table

The following table sets forth information concerning outstanding equity awards held by each of our named executive officers as of December 31, 2020:

	Option awards									Stock awards
Name	Number of securities underlying unexercised options (#) exercisable		Number of securities underlying unexercised options (#) unexercisable		Option exercise price ($/share)		Option expiration date			Number of shares of stock that have not vested (#)		Market value of shares of stock that have not vested ($)(1)
Markus Renschler, M.D.		—		216,146		0.35		2/24/2030	(2)		103,750		50,838
		—		362,500		0.30		12/10/2028	(3)		750,000		367,500
Andrew Gengos		—		501,334		0.35		3/23/2030	(4)		250,666		122,826
		—		188,000		0.35		3/23/2030	(5)		—		—
Paul Secrist, Ph.D.		—		752,000		0.35		7/21/2030	(6)		—		—
		—		188,000		0.35		7/21/2030	(7)		—		—

(1) Based on the estimated market value of a share of our common stock ($0.49) as determined by our board of directors taking into account an independent valuation analysis performed in September 2020, the closest valuation date to fiscal-year end.

(2) Represents an option to purchase 415,000 shares of our common stock granted on February 25, 2020, which vests in 48 equal monthly installments commencing on January 1, 2020, generally subject to Dr. Renschler’s continued employment with us through the applicable vesting date. Dr. Renschler early exercised 103,750 shares underlying this option and held 103,750 restricted shares of our common stock as of December 31, 2020, which restricted shares vest on the same schedule as the option award.

(3) Represents an option to purchase 2,550,000 shares of our common stock granted on December 19, 2018, which vests as to 62,500 shares underlying the award per month beginning February 3, 2019, generally subject to Dr. Renschler’s continued employment with us through the applicable vesting date. Dr. Renschler early exercised 750,000 shares underlying this option and held 750,000 restricted shares of our common stock as of December 31, 2020, which restricted shares vest on the same schedule as the option award.

(4) Represents an option to purchase 752,000 shares of our common stock granted on March 24, 2020, which vests as to 25% of the shares underlying the award on February 24, 2021 and as to the remaining shares underlying the award in 36 equal monthly installments thereafter, generally subject to Mr. Gengos’s continued employment with us through the applicable vesting date. Mr. Gengos early exercised 250,666 shares underlying this option and held 250,666 restricted shares of our common stock as of December 31, 2020, which restricted shares vest on the same schedule as the option award.

(5) Represents an option to purchase 188,000 shares of our common stock granted on March 24, 2020, which vests as to 75% of the shares underlying the award on February 24, 2023 and as to the remaining shares underlying the award in 12 equal monthly installments thereafter, generally subject to Mr. Gengos’s continued employment with us through the applicable vesting date.

(6) Represents an option to purchase 752,000 shares of our common stock granted on July 22, 2020, which vests as to 25% of the shares underlying the award on June 15, 2021 and as to the remaining shares underlying the award in 36 equal monthly installments thereafter, generally subject to Dr. Secrist’s continued employment with us through the applicable vesting date.

(7) Represents an option to purchase 188,000 shares of our common stock granted on July 22, 2020, which vests as to 75% of the shares underlying the award on June 15, 2023 and as to the remaining shares underlying the award in 12 equal monthly installments thereafter, generally subject to Dr. Secrist’s continued employment with us through the applicable vesting date.

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Director compensation

The following table sets forth the compensation awarded to, earned by or paid to our non-employee directors during the fiscal year ended December 31, 2020. Dr. Renschler’s compensation for 2020 is included with that of our other named executive officers above.

Name	Fees earned or paid in cash ($)(1)		Option awards ($)(2)		Total ($)
Racquel Bracken(3)		—		—		—
Jean George(3)		—		—		—
Karen Hong, Ph.D.(3)		—		—		—
Timothy Romberger(3)		—		—		—
Janwillem Naesens(3)		—		—		—
Joseph Zakrzewski		60,055		159,945		220,000
Susan Molineaux, Ph.D.(4)		1,438		54,735		56,173

(1) Amounts represent cash fees earned in fiscal 2020, pro-rated for the director’s service during the year.

(2) Amounts represent the aggregate grant date fair value of stock options granted to Mr. Zakrzewski and Dr. Molineaux during fiscal 2020 determined in accordance with ASC Topic 718. The underlying valuation assumptions for these stock option awards are discussed in Note 9 to our consolidated financial statements included elsewhere in this prospectus. As of December 31, 2020, Mr. Zakrzewski held 520,181 restricted shares of our common stock (received upon the early exercise of stock options held by him, as described below), and Dr. Molineaux held options to purchase 150,000 shares of our common stock.

(3) Directors who are affiliated with our investors do not receive compensation in respect of their service as members of our board of directors.

(4) Dr. Molineaux joined our board of directors on December 10, 2020.

Director compensation

Mr. Zakrzewski.    On June 10, 2020, in connection with his appointment as Chair of our board of directors, we entered into a letter agreement with Mr. Zakrzewski, pursuant to which he is entitled to receive an annual retainer of $80,000 effective as of May 12, 2020 and pro-rated for the 2020 calendar year to reflect service from May 12, 2020 through December 31, 2020 (prior to May 12, 2020, he was entitled to receive an annual retainer of $25,000). In addition to the June 13, 2020 equity grant described below, under the terms of his letter agreement, Mr. Zakrzewski was also entitled to receive a grant of stock options following the completion of our next private equity financing following the signing of the letter agreement led by an investor or investors who were not stockholders as of the date of the letter agreement (which has occurred) such that the shares that could be held by Mr. Zakrzewski as a result of exercise of stock options granted to him constitute 1% of our fully diluted equity as of immediately following the financing.

On March 24, 2020, Mr. Zakrzewski was granted an option to purchase 51,000 shares of our common stock, which vests in 24 equal monthly installments beginning on March 24, 2020. Pursuant to the terms of the letter agreement, on June 13, 2020, Mr. Zakrzewski was granted an option to purchase 563,500 shares of our common stock, which vests in 36 equal monthly installments beginning on May 12, 2020, subject to his continued service on our board of directors through the applicable vesting date.

If Mr. Zakrzewski is removed as a member of our board of directors other than for cause (as defined in his letter agreement), 50% of the outstanding stock options held by him will immediately vest and become exercisable. Upon the consummation of an acquisition, as defined in the 2012 Plan, all outstanding stock options held by Mr. Zakrzewski will immediately vest and become exercisable.

Following the amendment of our outstanding stock option award agreements in December 2020 to permit the early exercise of unvested stock options, Mr. Zakrzewski elected to early exercise a portion of his outstanding stock options on December 9, 2020, and, as of December 31, 2020, held 520,181 shares of restricted stock.

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Dr. Molineaux.    On December 9, 2020, in connection with her appointment to our board of directors, we entered into a letter agreement with Dr. Molineaux, pursuant to which she is entitled to receive an annual retainer of $25,000. Pursuant to the terms of the letter agreement, on December 9, 2020, Dr. Molineaux was granted an option to purchase 150,000 shares of our common stock, which vests in 36 equal monthly installments beginning on the date of the grant, subject to her continued service on our board of directors through the applicable vesting date.

Director compensation policy

In connection with this offering, we expect to adopt a formal non-employee director compensation policy, the terms of which will be described in a subsequent filing.

Equity and cash plans

2012 Stock Incentive Plan

In November 2012, our board of directors adopted the 2012 Plan. The 2012 Plan has been amended from time to time to, among other things, increase the aggregate number of shares of our common stock reserved for issuance under the plan, and was most recently amended in February 2021. The 2012 Plan permits the grant of stock options and other equity interests in the company, including restricted stock and restricted stock units. Subject to adjustment, the maximum number of shares that may be granted under the 2012 Plan is 23,661,918. As of                , 2021,                options,                shares of restricted stock and                restricted stock units were outstanding under the 2012 Plan and                  shares remained available for future issuance. No awards may be granted under the 2012 Plan after ten years from the date the 2012 Plan was adopted by our board of directors.

This summary is not a complete description of all provisions of the 2012 Plan and is qualified in its entirety by reference to the 2012 Plan and the amendments to the 2012 Plan, which are filed as exhibits to the registration statement of which this prospectus is part.

It is anticipated that no further awards will be made under the 2012 Plan following the completion of this offering. In connection with this offering, we intend to adopt a new omnibus equity plan under which we will grant equity-based awards in connection with or following this offering.

Plan administration

Our board of directors administers the 2012 Plan. Our board of directors may delegate any or all of its powers under the 2012 Plan as it may determine to one or more committees of our board of directors and, to the extent permitted by law, may delegate to one or more executive officers the power to grant awards and to exercise such other powers as our board of directors may determine. As used in this summary, the term “Administrator” refers to our board of directors and its authorized delegates, as applicable.

The Administrator has the discretionary authority to grant and amend awards, to adopt, amend and repeal rules relating to the 2012 Plan, to interpret, reconcile inconsistencies and correct the provisions of the 2012 Plan and any award and to modify and amend any award, subject to the limitations of the 2012 Plan.

Eligibility

Our employees, officers, directors, consultants and advisors, and those of our subsidiaries, are eligible to participate in the 2012 Plan. Eligibility for stock options intended to be incentive stock options, or ISOs, is limited to our employees.

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Types of awards

The 2012 Plan provides for the grant of stock options, restricted stock, restricted stock units, and other share-based awards.

Vesting; terms of awards

The Administrator determines the terms and conditions of all awards granted under the 2012 Plan, including the time or times an award vests or becomes exercisable, the terms and conditions on which an award remains exercisable and the effect of employment termination or other change in status of a participant on an award. The Administrator may at any time accelerate the vesting or exercisability of an award.

The Administrator may, without stockholder approval, amend any outstanding stock option to reduce its exercise price, and may cancel any outstanding stock option in exchange for a new stock option covering the same or a different number of shares of our common stock and having a lower exercise price than the cancelled stock option.

Transferability of awards

Except as the Administrator may otherwise determine or provide in an award, awards may not be transferred by the person to whom they are granted except by will or by the laws of descent and distribution or, in the case of a non-statutory stock option, pursuant to a qualified domestic relations order.

Effect of certain transactions

In the event of certain transactions (including the sale of the company by merger or consolidation, the sale, lease, exchange or other disposition of all or substantially all of the assets or capital stock of the company (other than in a spin-off or similar transaction) or any other acquisition of the business, as determined by our board of directors), the Administrator will, as to outstanding awards:

• make appropriate provision for the continuation of such awards by us or the assumption of such awards by the surviving entity by substituting on an equitable basis for the shares then subject to such awards either (1) the consideration payable in connection with the transaction, (2) shares of stock of the surviving entity or (3) other consideration as the Administrator deems appropriate;

• upon written notice, provide that the outstanding awards must be exercised, in whole or in part, within a specific number of days, at the end of which period such awards will terminate; or

• provide that the outstanding awards will terminate in exchange for a cash payment equal to the excess of the fair market value of the vested shares subject to such awards over the exercise price, if any.

Adjustment provisions

In the event of any stock split, reverse stock split, stock dividend, recapitalization, combination or reclassification of shares, spin-off, or other similar change in capitalization or event, the Administrator will adjust in a manner it deems to be appropriate (i) the number and class of securities available for awards under the 2012 Plan, (ii) the number and class of securities, vesting schedule and exercise price per share of each outstanding award, (iii) the repurchase price per security subject to repurchase and (iv) the terms of each other outstanding stock-based award. Alternatively, substitute awards may be made by the Administrator.

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Amendments and termination

The Administrator may amend, modify or terminate the 2012 Plan or any portion thereof at any time. In addition, the Administrator may amend any outstanding award granted pursuant to the 2012 Plan including, but not limited to, substituting another award of the same or a different type, changing the date of exercise or realization, and converting an incentive stock option to a non-statutory stock option; provided, that, the participant’s consent to any amendment is required unless the Administrator determines that the action, taking into account any anticipated consequences, would not materially and adversely affect the participant.

2021 Compensation plans

We expect that we will adopt a new equity incentive plan and a new cash incentive plan in connection with this offering, the terms of which will be described in a subsequent filing.

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Certain relationships and related party transactions

The following is a summary of transactions since January 1, 2019 to which we have been a party in which the amount involved exceeded $120,000 and in which any of our executive officers, directors, promoters or beneficial holders of more than 5% of our capital stock had or will have a direct or indirect material interest, other than compensation arrangements which are described under the section of this prospectus captioned “Executive and Director Compensation.”

Equity financings

Series B preferred stock

In September 2019, we completed the sale of our final tranche of Series B preferred stock resulting in an aggregate of 55,200,000 shares of our Series B preferred stock at a purchase price of $1.00 per share for an aggregate purchase price of $55,200,000. Each share of our Series B preferred stock will convert into one share of our common stock upon the closing of this offering.

The following table summarizes purchases of shares of our Series B preferred stock by holders of more than 5% of our capital stock and entities affiliated with our executive officers and members of our board of directors.

Name of stockholder	Director(s)/executive officer(s)		Shares of Series B preferred stock		Approximate purchase price
Entities affiliated with Droia Ventures(1)		Janwillem Naesens		10,000,000	$	10,000,000
Entities affiliated with Lightstone Ventures(2)		Jean George		7,500,000	$	7,500,000
Osage University Partners II, LP(3)		N/A		7,592,987	$	7,592,987
Novo Holdings A/S(4)		Karen Hong		14,000,000	$	14,000,000
Z Investments, LLC(5)		Joseph S. Zakrzewski		200,000	$	200,000
Entities affiliated with Venrock(6)		Racquel Bracken		10,000,000	$	10,000,000

(1) Droia Invest II SCSp is an affiliate of DFII GP Sàrl and of Wepaven BV, and is a holder of five percent or more of our capital stock. Mr. Naesens is a Director at Wepaven BV, which is a Manager at DFII GP Sàrl, which is the General Partner of Droia Invest II SCSp, and is a member of our board of directors.

(2) Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. together are holders of five percent or more of our capital stock. Ms. George is a Managing Director of LSV Associates II, LLC, the general partner of Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. and may be deemed to have shared voting and dispositive power with respect to the shares held by Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. Ms. George is a member of our board of directors.

(3) Osage University Partners II, LP is a holder of five percent or more of our capital stock.

(4) Novo Holdings A/S is a holder of five percent or more of our capital stock. Dr. Hong is employed as a Partner at Novo Ventures (US), Inc., which provides certain consultancy services to Novo Holdings A/S, and is a member of our board of directors. Dr. Hong is not deemed to hold any beneficiary ownership or reportable pecuniary interest in the shares held by Novo Holdings A/S.

(5) Joseph S. Zakrzewski is a managing member of Z Investments, LLC and is a member of our board of directors.

(6) Venrock Associates VII, L.P. and Venrock Partners VII, L.P. are holders of five percent or more of our capital stock. Racquel Bracken is a Partner at Venrock and is a member of our board of directors.

Series C preferred stock

In February 2021, we completed the sale of an aggregate of 21,784,885 shares of our Series C preferred stock at a purchase price of $3.67 per share for an aggregate purchase price of $79,999,980. Each share of our Series C preferred stock will convert into one share of our common stock upon the closing of this offering.

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The following table summarizes purchases of shares of our Series C preferred stock by holders of more than 5% of our capital stock and entities affiliated with our executive officers and members of our board of directors.

Name of stockholder	Director(s)/executive officer(s)		Shares of series C preferred stock		Approximate purchase price
Entities affiliated with Droia Ventures(1)		Janwillem Naesens		1,109,368	$	4,073,899
Entities affiliated with Lightstone Ventures(2)		Jean George		832,026	$	3,055,424
Novo Holdings A/S(3)		Karen Hong		1,553,116	$	5,703,461
Osage University Partners II, LP(4)		N/A		842,342	$	3,093,307
Entities affiliated with RA Capital Management, L.P.(5)		N/A		6,807,778	$	24,999,999
Entities affiliated with Venrock(6)		Racquel Bracken		1,109,368	$	4,073,899

(1) Droia Invest II SCSp is an affiliate of DFII GP Sàrl and of Wepaven BV, and is a holder of five percent or more of our capital stock. Mr. Naesens is a Director at Wepaven BV, which is a Manager at DFII GP Sàrl, which is the General Partner of Droia Invest II SCSp, and is a member of our board of directors.

(2) Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. together are holders of five percent or more of our capital stock. Ms. George is a Managing Director of LSV Associates II, LLC, the general partner of Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. and may be deemed to have shared voting and dispositive power with respect to the shares held by Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. Ms. George is a member of our board of directors.

(3) Novo Holdings A/S is a holder of five percent or more of our capital stock. Dr. Hong is employed as a Partner at Novo Ventures (US), Inc., which provides certain consultancy services to Novo Holdings A/S, and is a member of our board of directors. Dr. Hong is not deemed to hold any beneficiary ownership or reportable pecuniary interest in the shares held by Novo Holdings A/S.

(4) Osage University Partners II, LP is a holder of five percent or more of our capital stock.

(5) Consists of 5,786,611 shares of common stock issuable upon conversion of shares of Series C preferred stock held by RA Capital Healthcare Fund, L.P. (RA Healthcare) and 1,021,167 shares of common stock issuable upon conversion of Series C preferred stock held by RA Capital Nexus Fund II, L.P. (Nexus Fund). RA Capital Management, L.P. is the investment manager for RA Healthcare and Nexus Fund. The general partner of RA Capital Management, L.P. is RA Capital Management GP, LLC, of which Peter Kolchinsky and Rajeev Shah are the managing members. RA Capital Management, L.P., RA Capital Management GP, LLC, Peter Kolchinsky and Rajeev Shah may be deemed to have voting and investment power over the shares held of record by RA Healthcare and Nexus Fund. RA Capital Management, L.P., RA Capital Management GP, LLC, Peter Kolchinsky and Rajeev Shah disclaim beneficial ownership of such shares, except to the extent of any pecuniary interest therein.

(6) Venrock Associates VII, L.P. and Venrock Partners VII, L.P. are holders of five percent or more of our capital stock. Racquel Bracken is a Partner at Venrock and is a member of our board of directors.

Investor rights agreement

We are party to an amended and restated investor rights agreement, or the Investor Rights Agreement, with each holder of our preferred stock, which includes each holder of more than 5% of our capital stock and certain of our directors (or, in some cases, entities affiliated therewith). The Investor Rights Agreement imposes certain affirmative obligations on us, and also grants certain rights to the holders, including certain registration rights with respect to the registrable securities held by them. See “Description of Capital Stock—Registration Rights” for additional information regarding these registration rights. Other provisions of the Investor Rights Agreement will terminate upon completion of this offering.

Director and officer indemnification and insurance

We have agreed to indemnify each of our directors and executive officers against certain liabilities, costs and expenses, and have purchased directors’ and officers’ liability insurance. We also maintain a general liability insurance policy which covers certain liabilities of directors and officers arising out of claims based on acts or omissions in their capacities as directors or officers.

Related person transaction policy

Our board of directors intends to adopt a written related person transaction policy, to be effective upon the effectiveness of the registration statement of which this prospectus forms a part, setting forth the policies and

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procedures for the review and approval or ratification of related person transactions. This policy will cover, with certain exceptions set forth in Item 404 of Regulation S-K under the Securities Act of 1933, as amended, or the Securities Act, any transaction, arrangement or relationship, or any series of similar transactions, arrangements or relationships, in which we were or are to be a participant, where the amount involved exceeds $120,000 in any fiscal year and a related person had, has or will have a direct or indirect material interest, including without limitation, purchases of goods or services by or from the related person or entities in which the related person has a material interest, indebtedness, guarantees of indebtedness and employment by us of a related person. In reviewing and approving any such transactions, our audit committee is tasked with considering all relevant facts and circumstances, including, but not limited to, whether the transaction is on terms comparable to those that could be obtained in an arm’s length transaction and the extent of the related person’s interest in the transaction. All of the transactions described in this section occurred prior to the adoption of this policy.

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Principal stockholders

The following table sets forth certain information with respect to the beneficial ownership of our common stock at February 28, 2021, as adjusted to reflect the sale of common stock offered by us in this offering, for:

• each person who we know beneficially owns more than 5% of our common stock;

• each of our directors;

• each of our named executive officers; and

• all of our directors and executive officers as a group.

The number of shares beneficially owned by each stockholder is determined under rules issued by the SEC. Under these rules, a person is deemed to be a “beneficial” owner of a security if that person has or shares voting power or investment power, which includes the power to dispose of or to direct the disposition of such security. Except as indicated in the footnotes below, we believe, based on the information furnished to us, that the individuals and entities named in the table below have sole voting and investment power with respect to all shares of common stock beneficially owned by them, subject to any applicable community property laws.

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Percentage ownership of our common stock before this offering is based on 92,101,797 shares of our common stock outstanding as of February 28, 2021, after giving effect to the automatic conversion of all outstanding shares of our redeemable convertible preferred stock into 82,802,881 shares of our common stock immediately prior to the closing of this offering, assuming an initial public offering price of $        per share, which is the midpoint of the price range set forth on the cover page of this prospectus. Percentage ownership of our common stock after this offering is based on                shares of our common stock outstanding as of February 28, 2021, after giving effect to the automatic conversion of all outstanding shares of our redeemable convertible preferred stock as described above and our issuance of                shares of our common stock in this offering. In computing the number of shares beneficially owned by an individual or entity and the percentage ownership of that person, shares of common stock subject to options or other rights held by such person that are currently exercisable or that will become exercisable within 60 days of February 28, 2021, are considered outstanding, although these shares are not considered outstanding for purposes of computing the percentage ownership of any other person. Unless noted otherwise, the address of all listed stockholders is 128 Spring St, Building A, Suite 510, Lexington, MA 02421.

			Percentage of shares beneficially owned
Name of beneficial owner	Number of shares beneficially owned		Before offering		After offering
5% or greater stockholders
Celgene Corporation(1)		5,957,013		6.5%		%
Entities affiliated with Droia Ventures(2)		11,109,368		12.1%		%
Entities affiliated with Lightstone Ventures(3)		8,332,026		9.0%		%
Novo Holdings A/S(4)		15,553,116		16.9%		%
Osage University Partners II, LP(5)		8,435,329		9.2%		%
Entities affiliated with RA Capital Management, L.P.(6)		6,807,778		7.4%		%
Entities affiliated with Venrock(7)		11,109,368		12.1%		%
Directors and Named Executive Officers
Markus Renschler, M.D.(8)		2,918,815		3.2%		%
Andrew Gengos(9)		270,158		*		%
Paul Secrist, Ph.D.		—		—		%
Racquel Bracken		—		—		%
Jean George, M.B.A		—		—		%
Karen Hong, Ph.D.		—		—		%
Susan Molineaux, Ph.D.		—		—		%
Janwillem Naesens, M.Sc., M.B.A.		—		—		%
Timothy Romberger(10)		1,259,378		1.4%		%
Joseph S. Zakrzewski(11)		971,492		1.1%		%
All executive officers and directors as a group (10 persons)(12)		5,419,843		5.9%		%

* Less than 1%

(1) Consists of 2,000,000 shares of common stock issuable upon conversion of shares of Series A preferred stock and 3,957,013 shares of common stock issuable upon conversion of shares of Series B preferred stock. Celgene has the power to vote, acquire, hold and dispose of all such shares. Celgene disclaims beneficial ownership of these shares, except to the extent of its pecuniary interest therein. The mailing address of Celgene is 86 Morris Avenue, Summit, NJ 07901.

(2) Consists of 10,000,000 shares of common stock issuable upon conversion of shares of Series B preferred stock and 1,109,368 shares of common stock issuable upon conversion of shares of Series C preferred stock held by Droia Invest II SCSp. The mailing address of Droia Invest II SCSp is Boulevard Joseph II 28, L-1840, Luxembourg.

(3) Consists of 7,500,000 shares of common stock issuable upon conversion of shares of Series B preferred stock and 832,026 shares of common stock issuable upon conversion of shares of Series C preferred stock held by Lightstone Ventures II, L.P and Lightstone Ventures II (A), L.P. LSV Associates II, LLC is the general partner of Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. Ms. George, Michael A. Carusi, Henry

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A. Plain, Jr. and Jason W. Lettmann, the individual managing directors of LSV Associates II, LLC, share voting and dispositive power with respect to the shares held of record by Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. The mailing address of Lightstone Ventures II, L.P. and Lightstone Ventures II (A), L.P. is 500 Boylston Street, Suite 1380, Boston, MA 02116.

(4) Consists of 14,000,000 shares of common stock issuable upon conversion of shares of Series B preferred stock and 1,553,116 shares of common stock issuable upon conversion of shares of Series C preferred stock held by Novo Holdings A/S. The board of directors of Novo Holdings A/S (the Novo Board) has shared voting and investment power with respect to the shares held by Novo and may exercise such control only with the support of a majority of the members of the Novo Board. As such, no individual member of the Novo Board is deemed to hold any beneficial ownership or reportable pecuniary interest in the shares held by Novo. Dr. Hong, a member of our board of directors, is employed as a Partner at Novo Ventures (US), Inc., which provides certain consulting services to Novo Holdings A/S, and Dr. Hong is not deemed to have beneficial ownership of the shares held by Novo Holdings A/S. The address for Novo Holdings A/S is Tuborg Havnevej 19, DK-2900 Hellerup, Denmark.

(5) Consists of 7,592,987 shares of common stock issuable upon conversion of shares of Series B preferred stock and 842,342 shares of common stock issuable upon conversion of shares of Series C preferred stock held by Osage University Partners II, LP. The mailing address of Osage University Partners II, LP is 50 Monument Rd., Suite 201, Bala Cynwyd, Pennsylvania, 19004.

(6) Consists of 5,786,611 shares of common stock issuable upon conversion of shares of Series C preferred stock held by RA Capital Healthcare Fund, L.P. (RA Healthcare) and 1,021,167 shares of common stock issuable upon conversion of Series C preferred stock held by RA Capital Nexus Fund II, L.P. (Nexus Fund). RA Capital Management, L.P. is the investment manager for RA Healthcare and Nexus Fund. The general partner of RA Capital Management, L.P. is RA Capital Management GP, LLC, of which Peter Kolchinsky and Rajeev Shah are the managing members. RA Capital Management, L.P., RA Capital Management GP, LLC, Peter Kolchinsky and Rajeev Shah may be deemed to have voting and investment power over the shares held of record by RA Healthcare and Nexus Fund. RA Capital Management, L.P., RA Capital Management GP, LLC, Peter Kolchinsky and Rajeev Shah disclaim beneficial ownership of such shares, except to the extent of any pecuniary interest therein. The address of the entities listed above is 200 Berkeley Street, 18th Floor, Boston, Massachusetts 02116.

(7) Consists of 9,235,000 shares of common stock issuable upon conversion of shares of Series B preferred stock and 1,024,501 shares of common stock issuable upon conversion of shares of Series C preferred stock held by Venrock Associates VII, L.P. and 765,000 shares of common stock issuable upon conversion of shares of Series B preferred stock and 84,867 share of common stock issuable upon conversion of shares of Series C preferred stock held by Venrock Partners VII, L.P. The mailing address of Venrock Associates VII, L.P. and Venrock Partners VII, L.P. is 3340 Hillview Avenue, Palo Alto, CA 94304.

(8) Consists of 2,821,354 shares of common stock and options to purchase 97,461 shares of common stock that are exercisable within 60 days of February 28, 2021.

(9) Consists of 250,666 shares of common stock and options to purchase 19,492 shares of common stock that are exercisable within 60 days of February 28, 2021.

(10) Consists of 989,875 shares of common stock, 69,503 shares of common stock issuable upon conversion of shares of Series A preferred stock and 200,000 shares of common stock issuable upon conversion of shares of Series B preferred stock.

(11) Consists of 243,904 shares of common stock and options to purchase 19,492 shares of common stock that are exercisable within 60 days of February 28, 2021 held by Mr. Zakrzewski directly. Also includes (i) 508,096 shares of common stock held by Z3 Trust, for which Mr. Zakrzewski serves as trustee and (ii) 200,000 shares of common stock issuable upon conversion of shares of Series B preferred stock held by Z Investments, LLC. Mr. Zakrzewski serves as a managing member of Z Investments, LLC, and thus exercises voting and investment control over the securities held thereby.

(12) Consists of 5,013,895 shares of common stock, 69,503 shares of common stock issuable upon conversion of Series A preferred stock, 200,000 shares of common stock issuable upon conversion of Series B preferred stock and 136,445 shares of common stock that are exercisable within 60 days of February 28, 2021.

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Description of capital stock

Capital structure

The following description of our capital stock and certain provisions of our amended and restated certificate of incorporation and amended and restated by-laws are summaries and are qualified by reference to the amended and restated certificate of incorporation and the amended and restated by-laws that will be in effect upon the closing of this offering. Copies of these documents will be filed with the SEC as exhibits to our registration statement, of which this prospectus forms a part. The descriptions of our common stock and preferred stock reflect changes to our capital structure that will occur upon the closing of this offering.

General

Upon completion of this offering, our authorized capital stock will consist of            shares, par value of $0.001 per share, of which:

•              shares are designated as common stock; and

•              shares are designated as preferred stock.

Common stock

As of February 28, 2021, we had outstanding 9,298,916 shares of common stock held of record by 33 stockholders.

Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders and do not have cumulative voting rights. An election of directors by our stockholders shall be determined by a plurality of the votes cast by the stockholders entitled to vote on the election. Holders of common stock are entitled to receive proportionately any dividends as may be declared by our board of directors, subject to any preferential dividend rights of any series of preferred stock that we may designate and issue in the future.

In the event of our liquidation or dissolution, the holders of common stock are entitled to receive proportionately our net assets available for distribution to stockholders after the payment of all debts and other liabilities and subject to the prior rights of any outstanding preferred stock. Holders of common stock have no preemptive, subscription, redemption or conversion rights. Our outstanding shares of common stock are, and the shares offered by us in this offering will be, when issued and paid for, validly issued, fully paid and nonassessable. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.

Preferred stock

As of February 28, 2021 there were 82,802,881 shares of our redeemable convertible preferred stock outstanding. Upon the closing of this offering, all outstanding shares of our redeemable convertible preferred stock will convert into 82,802,881 shares of our common stock.

Under the terms of our amended and restated certificate of incorporation that will become effective immediately prior to the closing of this offering, our board of directors is authorized to direct us to issue shares of preferred stock in one or more series without stockholder approval. Our board of directors has the discretion to determine the rights, preferences, privileges and restrictions, including voting rights, dividend rights, conversion rights, redemption privileges and liquidation preferences, of each series of preferred stock.

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The purpose of authorizing our board of directors to issue preferred stock and determine its rights and preferences is to eliminate delays associated with a stockholder vote on specific issuances. The issuance of preferred stock, while providing flexibility in connection with possible acquisitions, future financings and other corporate purposes, could have the effect of making it more difficult for a third-party to acquire, or could discourage a third-party from seeking to acquire, a majority of our outstanding voting stock. Upon the closing of this offering, there will be no shares of preferred stock outstanding, and we have no present plans to issue any shares of preferred stock.

Stock options

As of February 28, 2021, options to purchase 8,453,312 shares of our common stock were outstanding under our 2012 Plan, of which 500,831 stock options were vested as of that date.

Registration rights

The Investor Rights Agreement grants the parties thereto certain registration rights in respect of the “registrable securities” held by them, which securities include (i) the shares of our common stock issuable or issued upon conversion of our preferred stock; (ii) any common stock held by investors party to the Investor Rights Agreement at the time of this offering; (iii) any common stock issued or issuable, directly or indirectly, upon conversion and/or exercise of any of our other securities held by the investors party to the Investor Rights Agreement at the time of this offering; and (iv) any common stock issued as, or issuable upon the conversion or exercise of any warrant, right or other security that is issued as, a dividend or other distribution with respect to, or in exchange for or in replacement of, the shares referenced in clauses (i), (ii) and (iii) above. The registration of shares of our common stock pursuant to the exercise of these registration rights would enable the holders thereof to sell such shares without restriction under the Securities Act when the applicable registration statement is declared effective. Under the Investor Rights Agreement, we will pay all expenses relating to such registrations, including the fees of one counsel for the participating holders, and the holders will pay all underwriting discounts and commissions relating to the sale of their shares. The Investor Rights Agreement also includes customary indemnification and procedural terms.

Holders of             shares of our common stock (including shares issuable upon the conversion of our redeemable convertible preferred stock) are entitled to such registration rights pursuant to the Investor Rights Agreement. These registration rights will expire on the earlier of (i) immediately before the closing of a deemed liquidation event, as defined in the Investor Rights Agreement; (ii) such time after this offering as SEC Rule 144 or another similar exemption under the Securities Act is available for the sale of all of such holder’s shares without limitation during a three-month period without registration; and (iii) the fifth anniversary of this offering.

Demand registration rights

At any time beginning 180 days after the effective date of the registration statement of which this prospectus forms a part, the holders of not less than a majority of the registrable securities then outstanding may request that we file a registration statement on Form S-1 with respect to at least forty percent (40%) of the registrable securities then outstanding or a lesser percent if the anticipated aggregate offering price, net of expenses, would exceed $15.0 million.

Once we are eligible to use a registration statement on Form S-3, the holders of not less than thirty percent (30%) of the registrable securities then outstanding may request that we file a registration statement on Form S-3 with respect to such registrable securities then outstanding, if the aggregate offering price of the registrable securities requested to be registered would exceed $2.0 million, net of expenses.

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Piggyback Registration Rights

In the event that we propose to register (including, for this purpose, a registration effected by us for stockholders other than the stockholders party to the Investor Rights Agreement) any of our common stock under the Securities Act in connection with the public offering of such securities solely for cash, the stockholders party to the Investor Rights Agreement will be entitled to certain “piggyback” registration rights allowing them to include their registrable securities in such registration, subject to certain marketing and other limitations. As a result, whenever we propose to file a registration statement under the Securities Act other than with respect to a demand registration or a registration statement on Form S-4 or S-8, these holders will be entitled to notice of the registration and will have the right to include their registrable securities in the registration subject to certain limitations.

Anti-takeover effects of our certificate of incorporation and our by-laws

Our certificate of incorporation and by-laws will contain certain provisions that are intended to enhance the likelihood of continuity and stability in the composition of our board of directors but which may have the effect of delaying, deferring or preventing a future takeover or change in control of us unless such takeover or change in control is approved by our board of directors.

These provisions include:

Classified board.    Our certificate of incorporation will provide that our board of directors will be divided into three classes of directors, with the classes as nearly equal in number as possible. As a result, approximately one-third of our board of directors will be elected each year. The classification of directors will have the effect of making it more difficult for stockholders to change the composition of our board. Our certificate of incorporation will also provide that, subject to any rights of holders of preferred stock to elect additional directors under specified circumstances, the number of directors will be fixed exclusively pursuant to a resolution adopted by our board of directors. Upon completion of this offering, we expect that our board of directors will have members.

Action by written consent; special meetings of stockholders.    Our certificate of incorporation will provide that stockholder action can be taken only at an annual or special meeting of stockholders and cannot be taken by written consent in lieu of a meeting. Our certificate of incorporation and the by-laws will also provide that, except as otherwise required by law, special meetings of the stockholders can only be called pursuant to a resolution adopted by a majority of our board of directors. Except as described above, stockholders will not be permitted to call a special meeting or to require our board of directors to call a special meeting.

Removal of directors.    Our certificate of incorporation will provide that our directors may be removed only for cause by the affirmative vote of at least 75% of the voting power of our outstanding shares of capital stock, voting together as a single class. This requirement of a supermajority vote to remove directors could enable a minority of our stockholders to prevent a change in the composition of our board.

Advance notice procedures.    Our by-laws will establish an advance notice procedure for stockholder proposals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to the board of directors. Stockholders at an annual meeting will only be able to consider proposals or nominations specified in the notice of meeting or brought before the meeting by or at the direction of our board of directors or by a stockholder who was a stockholder of record on the record date for the meeting, who is entitled to vote at the meeting and who has given our Secretary timely written notice, in proper form, of the stockholder’s intention to bring that business before the meeting. Although the by-laws will not give our board of directors the power to approve or disapprove stockholder nominations of candidates or proposals regarding

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other business to be conducted at a special or annual meeting, the by-laws may have the effect of precluding the conduct of certain business at a meeting if the proper procedures are not followed or may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect its own slate of directors or otherwise attempting to obtain control of us.

Supermajority approval requirements.    The DGCL generally provides that the affirmative vote of a majority of the shares entitled to vote on any matter is required to amend a corporation’s certificate of incorporation or by-laws, unless either a corporation’s certificate of incorporation or by-laws requires a greater percentage. Our certificate of incorporation and by-laws will provide that the affirmative vote of holders of at least 75% of the total votes eligible to be cast in the election of directors will be required to amend, alter, change or repeal specified provisions. This requirement of a supermajority vote to approve amendments to our certificate of incorporation and by-laws could enable a minority of our stockholders to exercise veto power over any such amendments.

Authorized but unissued shares.    Our authorized but unissued shares of common stock and preferred stock will be available for future issuance without stockholder approval. These additional shares may be utilized for a variety of corporate purposes, including future public offerings to raise additional capital, corporate acquisitions and employee benefit plans. The existence of authorized but unissued shares of common stock and preferred stock could render more difficult or discourage an attempt to obtain control of a majority of our common stock by means of a proxy contest, tender offer, merger or otherwise.

Exclusive forum.    Our amended and restated certificate of incorporation provides that, subject to limited exceptions, the state or federal courts within the State of Delaware will be exclusive forums for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or other employees to us or our stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the DGCL, our amended and restated certificate of incorporation or our amended and restated by-laws, (4) any action to interpret, apply, enforce or determine the validity of our amended and restated certificate of incorporation or our amended and restated bylaws or (5) any other action asserting a claim against us that is governed by the internal affairs doctrine; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Exchange Act or to any claim for which the federal courts have exclusive jurisdiction. Our amended and restated certificate of incorporation also provides that, unless we consent in writing to the selection of an alternative forum, the U.S. federal district courts shall be the exclusive forum for the resolution of any claims arising under the Securities Act. Although we believe these provisions benefit us by providing increased consistency in the application of Delaware and certain federal securities law, these provisions may have the effect of discouraging lawsuits against our directors and officers. See “Risk Factors—Risks Related to This Offering and Ownership of Our Common Stock—Our amended and restated certificate of incorporation designates the state or federal courts within the State of Delaware as the exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.”

Section 203 of the DGCL

Upon completion of this offering, we will be subject to the provisions of Section 203 of the DGCL. In general, Section 203 prohibits a publicly-held Delaware corporation from engaging in a “business combination” with an “interested stockholder” for a three-year period following the time that this stockholder becomes an interested stockholder, unless the business combination is approved in a prescribed manner. A “business combination” includes, among other things, a merger, asset or stock sale or other transaction resulting in a financial benefit to the interested stockholder. An “interested stockholder” is a person who, together with affiliates and

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associates, owns, or did own within three years prior to the determination of interested stockholder status, 15% or more of the corporation’s voting stock.

Under Section 203, a business combination between a corporation and an interested stockholder is prohibited unless it satisfies one of the following conditions: before the stockholder became interested, our board of directors approved either the business combination or the transaction which resulted in the stockholder becoming an interested stockholder; upon consummation of the transaction which resulted in the stockholder becoming an interested stockholder, the interested stockholder owned at least 85% of the voting stock of the corporation outstanding at the time the transaction commenced, excluding for purposes of determining the voting stock outstanding, shares owned by persons who are directors and also officers, and employee stock plans, in some instances; or at or after the time the stockholder became interested, the business combination was approved by our board of directors of the corporation and authorized at an annual or special meeting of the stockholders by the affirmative vote of at least two-thirds of the outstanding voting stock which is not owned by the interested stockholder.

A Delaware corporation may “opt out” of these provisions with an express provision in its original certificate of incorporation or an express provision in its certificate of incorporation or by-laws resulting from a stockholders’ amendment approved by at least a majority of the outstanding voting shares. We have not opted out of these provisions. As a result, mergers or other takeover or change in control attempts of us may be discouraged or prevented.

Transfer agent and registrar

The transfer agent and registrar for our common stock is                .

Listing

We have applied to have our common stock approved for listing on the                under the symbol “CYT.”

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Shares eligible for future sale

Immediately prior to this offering, there was no public market for our common stock, and no predictions can be made about the effect, if any, that market sales of our common stock or the availability of such shares for sale will have on the market price prevailing from time to time. Nevertheless, future sales of our common stock in the public market, or the perception that such sales may occur, could adversely affect the market price of our common stock and could impair our ability to raise capital through future sales of our securities. See “Risk Factors—Risks Related to This Offering and Ownership of Our Common Stock—A significant portion of our total outstanding shares is restricted from immediate resale but may be sold into the market in the near future, which could cause the market price of our common stock to decline significantly, even if our business is doing well.” Furthermore, although we have applied to have our common stock approved for listing on the                , we cannot assure you that there will be an active public trading market for our common stock.

Upon the closing of this offering, based on the number of shares of our common stock outstanding as of February 28, 2021 and after giving effect to the automatic conversion of all outstanding shares of our redeemable convertible preferred stock into                shares of our common stock immediately prior to the closing of this offering, we will have an aggregate of                shares of our common stock outstanding (or shares of our common stock if the underwriters exercise in full their option to purchase additional shares). Of these shares of our common stock, all of the                shares sold in this offering (or                shares if the underwriters exercise in full their option to purchase additional shares) will be freely tradable without restriction or further registration under the Securities Act, except for any shares purchased by our “affiliates,” as that term is defined in Rule 144 under the Securities Act, whose sales would be subject to the Rule 144 resale restrictions described below, other than the holding period requirement.

All remaining shares of common stock held by existing stockholders immediately prior to the completion of this offering will be “restricted securities” as such term is defined in Rule 144. These restricted securities are eligible for public sale only if they are registered under the Securities Act or if they qualify for an exemption from registration under Rules 144 or 701 under the Securities Act, which are summarized below. We expect that substantially all of these shares will be subject to the 180-day lock-up period under the lock-up agreements described below. Upon expiration of the lock-up period, we estimate that approximately                 shares of our common stock will be available for sale in the public market, subject in some cases to applicable volume limitations under Rule 144.

Lock-Up agreements

We and each of our directors and executive officers and holders of substantially all of our outstanding capital stock, who will collectively own                shares of our common stock upon the closing of this offering (based on our shares outstanding as of February 28, 2021 and after giving effect to the automatic conversion of all outstanding shares of our redeemable convertible preferred stock into shares of our common stock immediately prior to the closing of this offering), have agreed not to sell or transfer any common stock or securities convertible into, exchangeable for, exercisable for, or repayable with common stock, for 180 days after the date of this prospectus without first obtaining the written consent of the representatives of the underwriters.

Upon the expiration of the lock-up period, substantially all of the shares subject to such lock-up restrictions will become eligible for sale, subject to the limitations discussed above. For a further description of these lock-up agreements, please see “Underwriting.”

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Rule 144

Affiliate resales of restricted securities

In general, beginning 90 days after the effective date of the registration statement of which this prospectus is a part, a person who is an affiliate of ours, or who was an affiliate at any time during the 90 days before a sale, who has beneficially owned shares of our common stock for at least six months would be entitled to sell in “broker’s transactions” or certain “riskless principal transactions” or to market makers, a number of shares within any three-month period that does not exceed the greater of:

• 1% of the number of shares of our common stock then outstanding, which will equal approximately                  shares (or                shares if the underwriters exercise their option to purchase additional shares in full) of our common stock immediately after this offering; or

• the average weekly trading volume in shares of our common stock on the                during the four calendar weeks preceding the filing of a notice on Form 144 with respect to such sale.

Affiliate resales under Rule 144 are also subject to the availability of current public information about us. In addition, if the number of shares being sold under Rule 144 by an affiliate during any three-month period exceeds 5,000 shares or has an aggregate sale price in excess of $50,000, the seller must file a notice on Form 144 with the SEC and the                  concurrently with either the placing of a sale order with the broker or the execution directly with a market maker.

Non-affiliate resales of restricted securities

In general, beginning 90 days after the effective date of the registration statement of which this prospectus is a part, a person who is not an affiliate of ours at the time of sale, and has not been an affiliate at any time during the three months preceding a sale, and who has beneficially owned shares of our common stock for at least six months but less than a year, is entitled to sell such shares subject only to the availability of current public information about us. If such person has held our shares for at least one year, such person can resell under Rule 144(b)(1) without regard to any Rule 144 restrictions, including the 90-day public company requirement and the current public information requirement.

Non-affiliate resales are not subject to the manner of sale, volume limitation or notice filing provisions of Rule 144.

Rule 701

In general, under Rule 701, any of an issuer’s employees, directors, officers, consultants or advisors who purchases shares from the issuer in connection with a compensatory stock or option plan or other written agreement before the effective date of a registration statement under the Securities Act is entitled to sell such shares 90 days after such effective date in reliance on Rule 144. An affiliate of the issuer can resell shares in reliance on Rule 144 without having to comply with the holding period requirement, and non-affiliates of the issuer can resell shares in reliance on Rule 144 without having to comply with the current public information and holding period requirements.

The SEC has indicated that Rule 701 will apply to typical options granted by an issuer before it becomes subject to the reporting requirements of the Securities Exchange Act of 1934, as amended, or the Exchange Act, along with the shares acquired upon exercise of such options, including exercises after an issuer becomes subject to the reporting requirements of the Exchange Act.

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Equity plans

We intend to file one or more registration statements on Form S-8 under the Securities Act to register all shares of our common stock subject to outstanding options and shares of our common stock issued or issuable under our incentive plans. We expect to file the registration statement covering shares offered pursuant to our incentive plans shortly after the date of this prospectus, permitting the resale of such shares by nonaffiliates in the public market without restriction under the Securities Act and the sale by affiliates in the public market, subject to compliance with the resale provisions of Rule 144.

Registration rights

Upon the closing of this offering, the holders of                shares of our common stock (including shares of our common stock issuable upon the conversion of all outstanding shares of our redeemable convertible preferred stock) or their transferees will be entitled to various rights with respect to the registration of these shares under the Securities Act. Registration of these shares under the Securities Act would result in these shares becoming fully tradable without restriction under the Securities Act immediately upon the effectiveness of the registration, except for shares purchased by affiliates. See “Description of Capital Stock—Registration Rights” for additional information. Shares covered by a registration statement will be eligible for sale in the public market upon the expiration or release from the terms of the lock-up agreement.

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Material U.S. federal income tax consequences to non-U.S. holders of our common stock

The following discussion is a summary of the material U.S. federal income tax consequences to Non-U.S. Holders (as defined below) of the purchase, ownership and disposition of our common stock issued pursuant to this offering, but does not purport to be a complete analysis of all potential tax effects. The effects of other U.S. federal tax laws, such as estate and gift tax laws, and any applicable state, local or non-U.S. tax laws are not discussed. This discussion is based on the U.S. Internal Revenue Code of 1986, as amended, or the Code, Treasury Regulations promulgated thereunder, judicial decisions and published rulings and administrative pronouncements of the U.S. Internal Revenue Service, or the IRS, in each case, in effect as of the date hereof. These authorities may change or be subject to differing interpretations. Any such change or differing interpretation may be applied retroactively in a manner that could adversely affect a Non-U.S. Holder of our common stock. We have not sought and will not seek any rulings from the IRS regarding the matters discussed below. There can be no assurance the IRS or a court will not take a contrary position to that discussed below regarding the tax consequences of the purchase, ownership and disposition of our common stock.

This discussion is limited to Non-U.S. Holders that hold our common stock as a “capital asset” within the meaning of Section 1221 of the Code (generally, property held for investment). This discussion does not address all U.S. federal income tax consequences relevant to a Non-U.S. Holder’s particular circumstances, including the impact of the alternative minimum tax or the Medicare contribution tax on net investment income. In addition, it does not address consequences relevant to Non-U.S. Holders subject to special rules, including, without limitation:

• U.S. expatriates and former citizens or long-term residents of the United States;

• persons holding our common stock as part of a hedge, straddle or other risk reduction strategy or as part of a conversion transaction or other integrated investment;

• banks, insurance companies and other financial institutions;

• brokers, dealers or traders in securities;

• “controlled foreign corporations,” “passive foreign investment companies,” and corporations that accumulate earnings to avoid U.S. federal income tax;

• partnerships or other entities or arrangements treated as partnerships for U.S. federal income tax purposes (and investors therein);

• tax-exempt organizations or governmental organizations;

• persons deemed to sell our common stock under the constructive sale provisions of the Code;

• persons who hold or receive our common stock pursuant to the exercise of any employee stock option or otherwise as compensation;

• tax-qualified retirement plans;

• “qualified foreign pension funds” as defined in Section 897(l)(2) of the Code and entities all of the interests of which are held by qualified foreign pension funds; and

• persons subject to special tax accounting rules as a result of any item of gross income with respect to our common stock being taken into account in an applicable financial statement.

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This discussion does not address the tax treatment of partnerships or other pass-through entities, or arrangements, or persons who hold our common stock through partnerships or other pass-through entities or arrangements, for U.S. federal income tax purposes. If an entity or arrangement treated as a partnership for U.S. federal income tax purposes holds our common stock, the tax treatment of a partner in the partnership will depend on the status of the partner, the activities of the partnership and certain determinations made at the partner level. Accordingly, partnerships holding our common stock and the partners in such partnerships should consult their tax advisors regarding the U.S. federal income tax consequences to them.

THIS DISCUSSION IS FOR INFORMATIONAL PURPOSES ONLY AND IS NOT TAX ADVICE. INVESTORS SHOULD CONSULT THEIR TAX ADVISORS WITH RESPECT TO THE APPLICATION OF THE U.S. FEDERAL INCOME TAX LAWS TO THEIR PARTICULAR SITUATIONS, AS WELL AS ANY TAX CONSEQUENCES OF THE PURCHASE, OWNERSHIP AND DISPOSITION OF OUR COMMON STOCK ARISING UNDER THE U.S. FEDERAL ESTATE OR GIFT TAX LAWS OR UNDER THE LAWS OF ANY STATE, LOCAL OR NON-U.S. TAXING JURISDICTION OR UNDER ANY APPLICABLE INCOME TAX TREATY.

Definition of a Non-U.S. Holder

For purposes of this discussion, a “Non-U.S. Holder” is any beneficial owner of our common stock that is neither a “U.S. person” nor an entity or arrangement treated as a partnership for U.S. federal income tax purposes. A U.S. person is any person that, for U.S. federal income tax purposes, is or is treated as any of the following:

• an individual who is a citizen or resident of the United States;

• a corporation created or organized under the laws of the United States, any state thereof, or the District of Columbia;

• an estate, the income of which is subject to U.S. federal income tax regardless of its source; or

• a trust that (1) is subject to the primary supervision of a U.S. court and the control of one or more “United States persons” (within the meaning of Section 7701(a)(30) of the Code) or (2) has a valid election in effect to be treated as a United States person for U.S. federal income tax purposes.

Distributions

As described in the section entitled “Dividend Policy,” we do not anticipate declaring or paying any distributions to holders of our common stock in the foreseeable future. However, if we do make distributions of cash or property on our common stock, such distributions will constitute dividends for U.S. federal income tax purposes to the extent paid from our current or accumulated earnings and profits, as determined under U.S. federal income tax principles. Amounts not treated as dividends for U.S. federal income tax purposes will constitute a return of capital and first be applied against and reduce a Non-U.S. Holder’s adjusted tax basis in its common stock, but not below zero. Any remaining excess will be treated as capital gain and will be treated as described below under “—Sale or Other Taxable Disposition.”

Subject to the discussion below on effectively connected income, FATCA, and backup withholding, dividends paid to a Non-U.S. Holder of our common stock will be subject to U.S. federal withholding tax at a rate of 30% of the gross amount of the dividends or such lower rate specified by an applicable income tax treaty, provided the Non-U.S. Holder furnishes a valid IRS Form W-8BEN or W-8BEN-E (or other applicable documentation) certifying qualification for the lower treaty rate. A Non-U.S. Holder that does not timely furnish the required documentation, but that qualifies for a reduced treaty rate, may obtain a refund of any excess amounts withheld by timely filing an appropriate claim for refund with the IRS. Non-U.S. Holders should consult their tax advisors regarding their entitlement to benefits under any applicable income tax treaty.

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If dividends paid to a Non-U.S. Holder are effectively connected with the Non-U.S. Holder’s conduct of a trade or business within the United States (and, if required by an applicable income tax treaty, the Non-U.S. Holder maintains a permanent establishment in the United States to which such dividends are attributable), the Non-U.S. Holder will be exempt from the U.S. federal withholding tax described above. To claim the exemption, the Non-U.S. Holder must furnish to the applicable withholding agent a valid IRS Form W-8ECI, certifying that the dividends are effectively connected with the Non-U.S. Holder’s conduct of a trade or business within the United States.

Any such effectively connected dividends will be subject to U.S. federal income tax on a net income basis at the regular graduated rates. A Non-U.S. Holder that is a corporation also may be subject to a branch profits tax at a rate of 30% (or such lower rate specified by an applicable income tax treaty) on its effectively connected earnings and profits attributable to such dividends, as adjusted for certain items. Non-U.S. Holders should consult their tax advisors regarding any applicable tax treaties that may provide for different rules.

Sale or other taxable disposition

Subject to the discussion below on backup withholding and FATCA, a Non-U.S. Holder will not be subject to U.S. federal income tax on any gain realized upon the sale or other taxable disposition of our common stock unless:

• the gain is effectively connected with the Non-U.S. Holder’s conduct of a trade or business within the United States (and, if required by an applicable income tax treaty, the Non-U.S. Holder maintains a permanent establishment in the United States to which such gain is attributable);

• the Non-U.S. Holder is a nonresident alien individual present in the United States for 183 days or more during the taxable year of the disposition and certain other requirements are met; or

• our common stock constitutes a U.S. real property interest, or USRPI, by reason of our status as a U.S. real property holding corporation, or USRPHC, for U.S. federal income tax purposes.

Gain described in the first bullet point above generally will be subject to U.S. federal income tax on a net income basis at the regular graduated rates. A Non-U.S. Holder that is a corporation also may be subject to a branch profits tax at a rate of 30% (or such lower rate specified by an applicable income tax treaty) on its effectively connected earnings and profits attributable to such gain, as adjusted for certain items.

Gain described in the second bullet point above will be subject to U.S. federal income tax at a rate of 30% (or such lower rate specified by an applicable income tax treaty), but may be offset by certain U.S.-source capital losses (even though the individual is not considered a resident of the United States), provided that the Non-U.S. Holder has timely filed U.S. federal income tax returns with respect to such losses.

With respect to the third bullet point above, we believe we currently are not, and we do not anticipate becoming, a USRPHC. Because the determination of whether we are a USRPHC depends on the fair market value of our USRPIs relative to the fair market value of our non-U.S. real property interests and our other business assets, there can be no assurance we are not currently a USRPHC or will not become a USRPHC in the future. Even if we are or were to become a USRPHC, gain arising from the sale or other taxable disposition by a Non-U.S. Holder of our common stock will not be subject to U.S. federal income tax if our common stock is “regularly traded” (as defined by applicable Treasury Regulations) on an established securities market, and such Non-U.S. Holder owned, actually and constructively, 5% or less of our common stock throughout the shorter of the five-year period ending on the date of the sale or other taxable disposition or the Non-U.S. Holder’s holding period.

Non-U.S. Holders should consult their tax advisors regarding any applicable income tax treaties that may provide for different rules.

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Information reporting and backup withholding

Payments of dividends on our common stock will not be subject to backup withholding, provided the applicable withholding agent does not have actual knowledge or reason to know the holder is a United States person and the holder either certifies its non-U.S. status by furnishing a valid IRS Form W-8BEN, W-8BEN-E or W-8ECI or otherwise establishes an exemption. However, information returns are required to be filed with the IRS in connection with any distributions on our common stock paid to the Non-U.S. Holder, regardless of whether any distributions constitute dividends or of whether any tax was actually withheld. In addition, proceeds of the sale or other taxable disposition of our common stock within the United States or conducted through certain U.S.-related brokers generally will not be subject to backup withholding or information reporting, if the applicable withholding agent receives the certification described above and does not have actual knowledge or reason to know that such holder is a United States person or the holder otherwise establishes an exemption. Proceeds of a disposition of our common stock conducted through a non-U.S. office of a non-U.S. broker generally will not be subject to backup withholding or information reporting.

Copies of information returns that are filed with the IRS may also be made available under the provisions of an applicable treaty or agreement to the tax authorities of the country in which the Non-U.S. Holder resides or is established.

Backup withholding is not an additional tax. Any amounts withheld under the backup withholding rules may be allowed as a refund or a credit against a Non-U.S. Holder’s U.S. federal income tax liability, provided the required information is timely furnished to the IRS.

Additional withholding tax on payments made to foreign accounts

Withholding taxes may be imposed under Sections 1471 to 1474 of the Code, or FATCA, and related Treasury Regulations and guidance on certain types of payments made to non-U.S. financial institutions and certain other non-U.S. entities. Specifically, a 30% withholding tax may be imposed on dividends on our common stock paid to a “foreign financial institution” or a “non-financial foreign entity” (each as defined in the Code), unless (1) the foreign financial institution undertakes certain diligence and reporting obligations, (2) the non-financial foreign entity either certifies it does not have any “substantial United States owners” (as defined in the Code) or furnishes identifying information regarding each substantial United States owner, or (3) the foreign financial institution or non-financial foreign entity otherwise qualifies for an exemption from these rules. If the payee is a foreign financial institution and is subject to the diligence and reporting requirements in (1) above, it must enter into an agreement with the U.S. Department of the Treasury requiring, among other things, that it undertake to identify accounts held by certain “specified United States persons” or “United States-owned foreign entities” (each as defined in the Code), annually report certain information about such accounts, and withhold 30% on certain payments to non-compliant foreign financial institutions and certain other account holders. Foreign financial institutions located in jurisdictions that have an intergovernmental agreement with the United States governing FATCA may be subject to different rules.

Under the applicable Treasury Regulations and administrative guidance, withholding under FATCA generally applies to payments of dividends on our common stock. While withholding under FATCA would have also applied to payments of gross proceeds from the sale or other disposition of stock on or after January 1, 2019, proposed Treasury Regulations eliminate FATCA withholding on payments of gross proceeds entirely. Taxpayers generally may rely on these proposed Treasury Regulations until final Treasury Regulations are issued.

Prospective investors should consult their tax advisors regarding the potential application of withholding under FATCA to their investment in our common stock.

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Underwriting

We are offering the shares of common stock described in this prospectus through a number of underwriters. J.P. Morgan Securities LLC, Morgan Stanley & Co. LLC and BofA Securities, Inc. are acting as joint book-running managers of the offering and as representatives of the underwriters. We have entered into an underwriting agreement with the underwriters. Subject to the terms and conditions of the underwriting agreement, we have agreed to sell to the underwriters, and each underwriter has severally agreed to purchase, at the public offering price less the underwriting discounts and commissions set forth on the cover page of this prospectus, the number of shares of common stock listed next to its name in the following table:

Name	Number of shares
J.P. Morgan Securities LLC
Morgan Stanley & Co. LLC
BofA Securities, Inc.
Wedbush Securities Inc.
Total

The underwriters are committed to purchase all the common shares offered by us if they purchase any shares. The underwriting agreement also provides that if an underwriter defaults, the purchase commitments of non-defaulting underwriters may also be increased or the offering may be terminated.

The underwriters propose to offer the common shares directly to the public at the initial public offering price set forth on the cover page of this prospectus and to certain dealers at that price less a concession not in excess of $                 per share. Any such dealers may resell shares to certain other brokers or dealers at a discount of up to $                 per share from the initial public offering price. After the initial offering of the shares to the public, if all of the common shares are not sold at the initial public offering price, the underwriters may change the offering price and the other selling terms. Sales of any shares made outside of the United States may be made by affiliates of the underwriters.

The underwriters have an option to buy up to                  additional shares of common stock from us to cover sales of shares by the underwriters which exceed the number of shares specified in the table above. The underwriters have 30 days from the date of this prospectus to exercise this option to purchase additional shares. If any shares are purchased with this option to purchase additional shares, the underwriters will purchase shares in approximately the same proportion as shown in the table above. If any additional shares of common stock are purchased, the underwriters will offer the additional shares on the same terms as those on which the shares are being offered.

The underwriting fee is equal to the public offering price per share of common stock less the amount paid by the underwriters to us per share of common stock. The underwriting fee is $                 per share. The following table shows the per share and total underwriting discounts and commissions to be paid to the underwriters assuming both no exercise and full exercise of the underwriters’ option to purchase additional shares.

	Without option to purchase additional shares exercise	With full option to purchase additional shares exercise
Per Share	$	$
Total	$	$

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We estimate that the total expenses of this offering, including registration, filing and listing fees, printing fees and legal and accounting expenses, but excluding the underwriting discounts and commissions, will be approximately $            .

A prospectus in electronic format may be made available on the web sites maintained by one or more underwriters, or selling group members, if any, participating in the offering. The underwriters may agree to allocate a number of shares to underwriters and selling group members for sale to their online brokerage account holders. Internet distributions will be allocated by the representatives to underwriters and selling group members that may make Internet distributions on the same basis as other allocations.

We have agreed that we will not (i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, lend or otherwise transfer or dispose of, directly or indirectly, or submit to, or file with, the Securities and Exchange Commission a registration statement under the Securities Act relating to, any shares of our common stock or securities convertible into or exercisable or exchangeable for any shares of our common stock, or publicly disclose the intention to make any offer, sale, pledge, loan, disposition or filing, or (ii) enter into any swap or other arrangement that transfers all or a portion of the economic consequences associated with the ownership of any shares of common stock or any such other securities (regardless of whether any of these transactions are to be settled by the delivery of shares of common stock or such other securities, in cash or otherwise), in each case without the prior written consent of the representatives of the underwriters for a period of 180 days after the date of this prospectus, other than the shares of our common stock to be sold in this offering.

The restrictions on our actions, as described above, do not apply to certain transactions, including (i) the issuance of shares of common stock or securities convertible into or exercisable for shares of our common stock pursuant to the conversion or exchange of convertible or exchangeable securities or the exercise of warrants or options (including net exercise) or the settlement of RSUs (including net settlement), in each case outstanding on the date of the underwriting agreement and described in this prospectus; (ii) grants of stock options, stock awards, restricted stock, RSUs, or other equity awards and the issuance of shares of our common stock or securities convertible into or exercisable or exchangeable for shares of our common stock (whether upon the exercise of stock options or otherwise) to our employees, officers, directors, advisors, or consultants pursuant to the terms of an equity compensation plan in effect as of the closing of this offering and described in this prospectus, (iii) our filing of any registration statement on Form S-8 relating to securities granted or to be granted pursuant to any plan in effect on the date of the underwriting agreement and described in this prospectus or any assumed benefit plan pursuant to an acquisition or similar strategic transaction, (iv) facilitating of the establishment of a trading plan pursuant to Rule 10b5-1 under the Exchange Act for the transfer of shares of common stock by a shareholder, director or officer, provided that (a) such plan does not provide for the transfer of common stock during the restricted period and (b) to the extent a public announcement or filing under the Exchange Act, if any, is required of or voluntarily made by the Company regarding the establishment of such plan, such announcement or filing shall include a statement to the effect that no transfer of common stock may be made under such plan during the restricted period, or (v) our issuance of common stock or any securities convertible into, or exercisable or exchangeable for, common stock, or the entrance into an agreement to issue common stock or any securities convertible into, or exercisable or exchangeable for, common stock, in connection with any merger, joint venture, strategic alliances, commercial or other collaborative transaction or the acquisition or license of the business, property, technology or other assets of another individual or entity or the assumption of an employee benefit plan in connection with a merger or acquisition; provided that (x) the aggregate number of shares of common stock issued or issuable pursuant to this clause (v) shall not exceed ten percent (10%) of the total number of shares of common stock issued and outstanding immediately following the offering and (y) the recipient of any such shares of our

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common stock or securities issued pursuant this clause (v) during the lock-up period shall enter into (if it has not previously entered into) a lock-up agreement.

Our directors and executive officers, and our shareholders holding in the aggregate approximately    % of the outstanding shares of our common stock (such persons, the “lock-up parties”) have entered into lock-up agreements with the underwriters prior to the commencement of this offering pursuant to which each lock-up party, with limited exceptions, for a period of 180 days after the date of this prospectus (such period, the “restricted period”), may not (and may not cause any of their direct or indirect affiliates to), without the prior written consent of the representatives of the underwriters, (1) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, lend or otherwise transfer or dispose of, directly or indirectly, any shares of our common stock or any securities convertible into or exercisable or exchangeable for our common stock (including, without limitation, common stock or such other securities which may be deemed to be beneficially owned by such lock-up parties in accordance with the rules and regulations of the SEC and securities which may be issued upon exercise of a stock option or warrant (collectively with the common stock, the “lock-up securities”)), (2) enter into any hedging, swap or other agreement or transaction that transfers, in whole or in part, any of the economic consequences of ownership of the lock-up securities, whether any such transaction described in clause (1) or (2) above is to be settled by delivery of lock-up securities, in cash or otherwise, (3) make any demand for, or exercise any right with respect to, the registration of any lock-up securities, or (4) publicly disclose the intention to do any of the foregoing. Such persons or entities have further acknowledged that these undertakings preclude them from engaging in any hedging or other transactions or arrangements (including, without limitation, any short sale or the purchase or sale of, or entry into, any put or call option, or combination thereof, forward, swap or any other derivative transaction or instrument, however described or defined) designed or intended, or which could reasonably be expected to lead to or result in, a sale or disposition or transfer (by any person or entity, whether or not a signatory to such agreement) of any economic consequences of ownership, in whole or in part, directly or indirectly, of any lock-up securities, whether any such transaction or arrangement (or instrument provided for thereunder) would be settled by delivery of lock-up securities, in cash or otherwise.

The restrictions described in the immediately preceding paragraph and contained in the lock-up agreements between the underwriters and the lock-up parties do not apply, subject in certain cases to various conditions, to certain transactions, including (a) transfers of lock-up securities: (i) as a bona fide gift or gifts, or to a charitable organization or educational institution, or for bona fide estate planning purposes, (ii) by will or other testamentary document, or by intestacy, (iii) to any trust for the direct or indirect benefit of the lock-up party or any immediate family member, (iv) to a partnership, limited liability company or other entity of which the lock-up party and its immediate family members control or manage, (v) to a nominee or custodian of a person or entity to whom a disposition or transfer would be permissible under clauses (i) through (iv), (vi) in the case of a corporation, partnership, limited liability company, trust or other business entity, (A) to another corporation, partnership, limited liability company, trust or other business entity that is an affiliate of the lock-up party, or to any investment fund or other entity controlling, controlled by, managing or managed by or under common control with the lock-up party or its affiliates or (B) as part of a distribution to members, limited partners or stockholders of the lock-up party; (vii) by operation of law or pursuant to an order of a court or regulatory agency, (viii) to us from an employee or service provider upon death, disability, termination of service or termination of employment of such employee or service provider, (ix) as part of a sale of lock-up securities acquired in this offering or in open market transactions after the pricing of this offering, (x) to us in connection with the vesting, settlement or exercise of restricted stock units, options, warrants or other rights to purchase shares of our common stock (including “net” or “cashless” exercise), including for the payment of exercise price and tax and remittance payments, or (xi) pursuant to a bona fide third-party tender offer, merger, consolidation or other similar transaction approved by our board of directors and made to all shareholders involving a

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change in control, provided that if such transaction is not completed, all such lock-up securities would remain subject to the restrictions in the immediately preceding paragraph; provided further (A) that in the case of any transfer or distribution pursuant to clauses (a)(i), (ii), (iii), (iv), (v) and (vi), each donee, devisee, transferee or distributee shall be subject to the lock-up restrictions, (B) in the case of any transfer or distribution pursuant to clause (a)(i), (ii), (iii), (iv), (v), (vi), (vii), (ix) and (x), no filing by any party under the Exchange Act or other public announcement shall be required or shall be made voluntarily in connection with such transfer or distribution reporting a reduction in beneficial ownership of shares of common stock (other than a filing on a Form 5 or Schedule 13 made after the expiration of the restricted period) and (C) in the case of any transfer or distribution pursuant to clause (a)(vii) and (viii) it shall be a condition to such transfer that no public filing, report or announcement shall be voluntarily made and if any filing under Section 16(a) of the Exchange Act, or other public filing, report or announcement reporting a reduction in beneficial ownership of shares of common stock in connection with such transfer or distribution shall be legally required during the restricted period, such filing, report or announcement shall clearly indicate in the footnotes thereto the nature and conditions of such transfer; (b) exercise of the options, settlement of RSUs or other equity awards, or the exercise of warrants granted pursuant to plans described in this prospectus, provided that any lock-up securities received upon such exercise, vesting or settlement would be subject to restrictions similar to those in the immediately preceding paragraph; (c) the conversion of outstanding preferred stock, warrants to acquire preferred stock, or convertible securities into shares of our common stock or warrants to acquire shares of our common stock, provided that any common stock or warrant received upon such conversion would be subject to restrictions similar to those in the immediately preceding paragraph; and (d) the establishment by lock-up parties of trading plans under Rule 10b5-1 under the Exchange Act, provided that such plan does not provide for the transfer of lock-up securities during the restricted period.

The representatives of the underwriters, in their sole discretion, may release the securities subject to any of the lock-up agreements with the underwriters described above, in whole or in part at any time.

Record holders of our securities are typically the parties to the lock-up agreements with the underwriters and the market standoff agreements with us referred to above, while holders of beneficial interests in our shares who are not also record holders in respect of such shares are not typically subject to any such agreements or other similar restrictions. Accordingly, we believe that certain holders of beneficial interests who are not record holders and are not bound by market standoff or lock-up agreements could enter into transactions with respect to those beneficial interests that negatively impact our stock price. In addition, an shareholder who is neither subject to a market standoff agreement with us nor a lock-up agreement with the underwriters may be able to sell, short sell, transfer, hedge, pledge, lend or otherwise dispose of or attempt to sell short sell, transfer, hedge, pledge, lend or otherwise dispose of, their equity interests at any time after the closing of this offering.

We have agreed to indemnify the underwriters against certain liabilities, including liabilities under the Securities Act of 1933.

We will apply to have our common stock approved for listing/quotation on                  under the symbol “CYT”.

In connection with this offering, the underwriters may engage in stabilizing transactions, which involves making bids for, purchasing and selling shares of common stock in the open market for the purpose of preventing or retarding a decline in the market price of the common stock while this offering is in progress. These stabilizing transactions may include making short sales of common stock, which involves the sale by the underwriters of a greater number of shares of common stock than they are required to purchase in this offering, and purchasing shares of common stock on the open market to cover positions created by short sales. Short sales may be “covered” shorts, which are short positions in an amount not greater than the underwriters’ option to purchase additional shares referred to above, or may be “naked” shorts, which are short positions in excess of that

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amount. The underwriters may close out any covered short position either by exercising their option to purchase additional shares, in whole or in part, or by purchasing shares in the open market. In making this determination, the underwriters will consider, among other things, the price of shares available for purchase in the open market compared to the price at which the underwriters may purchase shares through the option to purchase additional shares. A naked short position is more likely to be created if the underwriters are concerned that there may be downward pressure on the price of the common stock in the open market that could adversely affect investors who purchase in this offering. To the extent that the underwriters create a naked short position, they will purchase shares in the open market to cover the position.

The underwriters have advised us that, pursuant to Regulation M of the Securities Act of 1933, they may also engage in other activities that stabilize, maintain or otherwise affect the price of the common stock, including the imposition of penalty bids. This means that if the representatives of the underwriters purchase common stock in the open market in stabilizing transactions or to cover short sales, the representatives can require the underwriters that sold those shares as part of this offering to repay the underwriting discount received by them.

These activities may have the effect of raising or maintaining the market price of the common stock or preventing or retarding a decline in the market price of the common stock, and, as a result, the price of the common stock may be higher than the price that otherwise might exist in the open market. If the underwriters commence these activities, they may discontinue them at any time. The underwriters may carry out these transactions on the                 , in the over-the-counter market or otherwise.

Prior to this offering, there has been no public market for our common stock. The initial public offering price will be determined by negotiations between us and the representatives of the underwriters. In determining the initial public offering price, we and the representatives of the underwriters expect to consider a number of factors including:

• the information set forth in this prospectus and otherwise available to the representatives;

• our prospects and the history and prospects for the industry in which we compete;

• an assessment of our management;

• our prospects for future earnings;

• the general condition of the securities markets at the time of this offering;

• the recent market prices of, and demand for, publicly traded common stock of generally comparable companies; and

• other factors deemed relevant by the underwriters and us.

Neither we nor the underwriters can assure investors that an active trading market will develop for our common shares, or that the shares will trade in the public market at or above the initial public offering price.

Other than in the United States, no action has been taken by us or the underwriters that would permit a public offering of the securities offered by this prospectus in any jurisdiction where action for that purpose is required. The securities offered by this prospectus may not be offered or sold, directly or indirectly, nor may this prospectus or any other offering material or advertisements in connection with the offer and sale of any such securities be distributed or published in any jurisdiction, except under circumstances that will result in compliance with the applicable rules and regulations of that jurisdiction. Persons into whose possession this prospectus comes are advised to inform themselves about and to observe any restrictions relating to the offering and the distribution of this prospectus. This prospectus does not constitute an offer to sell or a

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solicitation of an offer to buy any securities offered by this prospectus in any jurisdiction in which such an offer or a solicitation is unlawful.

Certain of the underwriters and their affiliates have provided in the past to us and our affiliates and may provide from time to time in the future certain commercial banking, financial advisory, investment banking and other services for us and such affiliates in the ordinary course of their business, for which they have received and may continue to receive customary fees and commissions. In addition, from time to time, certain of the underwriters and their affiliates may effect transactions for their own account or the account of customers, and hold on behalf of themselves or their customers, long or short positions in our debt or equity securities or loans, and may do so in the future.

Selling restrictions

Notice to prospective investors in the European Economic Area

In relation to each Member State of the European Economic Area (each a “Member State”), no shares have been offered or will be offered pursuant to the offering to the public in that Member State prior to the publication of a prospectus in relation to the shares which has been approved by the competent authority in that Member State or, where appropriate, approved in another Member State and notified to the competent authority in that Member State, all in accordance with the Prospectus Regulation, except that offers of shares may be made to the public in that Member State at any time under the following exemptions under the Prospectus Regulation:

(A) to any legal entity which is a qualified investor as defined under the Prospectus Regulation;

(B) to fewer than 150 natural or legal persons (other than qualified investors as defined under the Prospectus Regulation), subject to obtaining the prior consent of the underwriters; or

(C) in any other circumstances falling within Article 1(4) of the Prospectus Regulation,

provided that no such offer of shares shall require us or any underwriter to publish a prospectus pursuant to Article 3 of the Prospectus Regulation or supplement a prospectus pursuant to Article 23 of the Prospectus Regulation and each person who initially acquires any shares or to whom any offer is made will be deemed to have represented, acknowledged and agreed to and with each of the underwriters and the Company that it is a “qualified investor” within the meaning of Article 2(e) of the Prospectus Regulation. In the case of any shares being offered to a financial intermediary as that term is used in the Prospectus Regulation, each such financial intermediary will be deemed to have represented, acknowledged and agreed that the shares acquired by it in the offer have not been acquired on a non-discretionary basis on behalf of, nor have they been acquired with a view to their offer or resale to, persons in circumstances which may give rise to an offer of any shares to the public other than their offer or resale in a Member State to qualified investors as so defined or in circumstances in which the prior consent of the underwriters have been obtained to each such proposed offer or resale.

For the purposes of this provision, the expression an “offer to the public” in relation to shares in any Member State means the communication in any form and by any means of sufficient information on the terms of the offer and any shares to be offered so as to enable an investor to decide to purchase or subscribe for any shares, and the expression “Prospectus Regulation” means Regulation (EU) 2017/1129.

Notice to prospective investors in the United Kingdom

In addition, in the United Kingdom, this document is being distributed only to, and is directed only at, and any offer subsequently made may only be directed at persons who are “qualified investors” (as defined in the Prospectus Regulation) (i) who have professional experience in matters relating to investments falling within

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Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the “Order”) and/or (ii) who are high net worth companies (or persons to whom it may otherwise be lawfully communicated) falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as “relevant persons”) or otherwise in circumstances which have not resulted and will not result in an offer to the public of the shares in the United Kingdom within the meaning of the Financial Services and Markets Act 2000.

Any person in the United Kingdom that is not a relevant person should not act or rely on the information included in this document or use it as basis for taking any action. In the United Kingdom, any investment or investment activity that this document relates to may be made or taken exclusively by relevant persons.

Notice to prospective investors in Canada

The shares may be sold only to purchasers purchasing, or deemed to be purchasing, as principal that are accredited investors, as defined in National Instrument 45-106 Prospectus Exemptions or subsection 73.3(1) of the Securities Act (Ontario), and are permitted clients, as defined in National Instrument 31-103 Registration Requirements, Exemptions and Ongoing Registrant Obligations. Any resale of the shares must be made in accordance with an exemption from, or in a transaction not subject to, the prospectus requirements of applicable securities laws.

Securities legislation in certain provinces or territories of Canada may provide a purchaser with remedies for rescission or damages if this prospectus (including any amendment thereto) contains a misrepresentation, provided that the remedies for rescission or damages are exercised by the purchaser within the time limit prescribed by the securities legislation of the purchaser’s province or territory. The purchaser should refer to any applicable provisions of the securities legislation of the purchaser’s province or territory for particulars of these rights or consult with a legal advisor.

Pursuant to section 3A.3 of National Instrument 33-105 Underwriting Conflicts (NI 33-105), the underwriters are not required to comply with the disclosure requirements of NI 33-105 regarding underwriter conflicts of interest in connection with this offering.

Notice to prospective investors in Switzerland

The shares may not be publicly offered in Switzerland and will not be listed on the SIX Swiss Exchange (“SIX”) or on any other stock exchange or regulated trading facility in Switzerland. This document does not constitute a prospectus within the meaning of, and has been prepared without regard to the disclosure standards for issuance prospectuses under art. 652a or art. 1156 of the Swiss Code of Obligations or the disclosure standards for listing prospectuses under art. 27 ff. of the SIX Listing Rules or the listing rules of any other stock exchange or regulated trading facility in Switzerland. Neither this document nor any other offering or marketing material relating to the shares or the offering may be publicly distributed or otherwise made publicly available in Switzerland.

Neither this document nor any other offering or marketing material relating to the offering, the Company, the shares have been or will be filed with or approved by any Swiss regulatory authority. In particular, this document will not be filed with, and the offer of shares will not be supervised by, the Swiss Financial Market Supervisory Authority FINMA (FINMA), and the offer of shares has not been and will not be authorized under the Swiss Federal Act on Collective Investment Schemes (“CISA”). The investor protection afforded to acquirers of interests in collective investment schemes under the CISA does not extend to acquirers of shares.

Notice to prospective investors in Hong Kong

The shares have not been offered or sold and will not be offered or sold in Hong Kong, by means of any document, other than (a) to “professional investors” as defined in the Securities and Futures Ordinance

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(Cap. 571 of the Laws of Hong Kong) (the “SFO”) of Hong Kong and any rules made thereunder; or (b) in other circumstances which do not result in the document being a “prospectus” as defined in the Companies (Winding Up and Miscellaneous Provisions) Ordinance (Cap. 32) of Hong Kong) (the “CO”) or which do not constitute an offer to the public within the meaning of the CO. No advertisement, invitation or document relating to the shares has been or may be issued or has been or may be in the possession of any person for the purposes of issue, whether in Hong Kong or elsewhere, which is directed at, or the contents of which are likely to be accessed or read by, the public of Hong Kong (except if permitted to do so under the securities laws of Hong Kong) other than with respect to shares which are or are intended to be disposed of only to persons outside Hong Kong or only to “professional investors” as defined in the SFO and any rules made thereunder.

Notice to prospective investors in Singapore

Each representative has acknowledged that this prospectus has not been registered as a prospectus with the Monetary Authority of Singapore. Accordingly, each representative has represented and agreed that it has not offered or sold any shares or caused the shares to be made the subject of an invitation for subscription or purchase and will not offer or sell any shares or cause the shares to be made the subject of an invitation for subscription or purchase, and has not circulated or distributed, nor will it circulate or distribute, this prospectus or any other document or material in connection with the offer or sale, or invitation for subscription or purchase, of the shares, whether directly or indirectly, to any person in Singapore other than:

(A) to an institutional investor (as defined in Section 4A of the Securities and Futures Act (Chapter 289) of Singapore, as modified or amended from time to time (the “SFA”)) pursuant to Section 274 of the SFA;

(B) to a relevant person (as defined in Section 275(2) of the SFA) pursuant to Section 275(1) of the SFA, or any person pursuant to Section 275(1A) of the SFA, and in accordance with the conditions specified in Section 275 of the SFA; or

(C) otherwise pursuant to, and in accordance with the conditions of, any other applicable provision of the SFA.

Where the shares are subscribed or purchased under Section 275 of the SFA by a relevant person which is:

(A) a corporation (which is not an accredited investor (as defined in Section 4A of the SFA)) the sole business of which is to hold investments and the entire share capital of which is owned by one or more individuals, each of whom is an accredited investor; or

(B) a trust (where the trustee is not an accredited investor) whose sole purpose is to hold investments and each beneficiary of the trust is an individual who is an accredited investor,

securities or securities-based derivatives contracts (each term as defined in Section 2(1) of the SFA) of that corporation or the beneficiaries’ rights and interest (howsoever described) in that trust shall not be transferred within six months after that corporation or that trust has acquired the shares pursuant to an offer made under Section 275 of the SFA except:

(A) to an institutional investor or to a relevant person, or to any person arising from an offer referred to in Section 275(1A) or Section 276(4)(i)(B) of the SFA;

(B) where no consideration is or will be given for the transfer;

(C) where the transfer is by operation of law;

(D) as specified in Section 276(7) of the SFA; or

(E) as specified in Regulation 37A of the Securities and Futures (Offers of Investments) (Securities and Securities-based Derivatives Contracts) Regulations 2018.

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Notice to prospective investors in Japan

The shares have not been and will not be registered pursuant to Article 4, Paragraph 1 of the Financial Instruments and Exchange Act. Accordingly, none of the shares nor any interest therein may be offered or sold, directly or indirectly, in Japan or to, or for the benefit of, any “resident” of Japan (which term as used herein means any person resident in Japan, including any corporation or other entity organized under the laws of Japan), or to others for re-offering or resale, directly or indirectly, in Japan or to or for the benefit of a resident of Japan, except pursuant to an exemption from the registration requirements of, and otherwise in compliance with, the Financial Instruments and Exchange Act and any other applicable laws, regulations and ministerial guidelines of Japan in effect at the relevant time.

Notice to prospective investors in the United Arab Emirates

The shares have not been, and are not being, publicly offered, sold, promoted or advertised in the United Arab Emirates (including the Dubai International Financial Centre) other than in compliance with the laws of the United Arab Emirates (and the Dubai International Financial Centre) governing the issue, offering and sale of securities. Further, this prospectus does not constitute a public offer of securities in the United Arab Emirates (including the Dubai International Financial Centre) and is not intended to be a public offer. This prospectus has not been approved by or filed with the Central Bank of the United Arab Emirates, the Securities and Commodities Authority or the Dubai Financial Services Authority.

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Legal matters

The validity of the shares of common stock offered by this prospectus will be passed upon for us by Ropes & Gray, LLP, Boston, Massachusetts. Certain legal matters will be passed upon for the underwriters by Davis Polk & Wardwell LLP, New York, New York.

Experts

The consolidated financial statements of Cyteir Therapeutics, Inc. as of and for the years ended December 31, 2020 and 2019 included in this prospectus have been audited by Ernst & Young, an independent registered public accounting firm, as stated in their report thereon appearing elsewhere herein, and are included in reliance upon such report given on the authority of such firm as experts in accounting and auditing.

Where you can find additional information

We have filed with the SEC a registration statement on Form S-1 under the Securities Act of 1933, as amended, with respect to the shares of common stock offered hereby. This prospectus, which constitutes a part of the registration statement, does not contain all of the information set forth in the registration statement or the exhibits and schedules filed therewith. For further information about us and the shares of common stock offered hereby, we refer you to the registration statement and the exhibits and schedules filed thereto. Statements contained in this prospectus regarding the contents of any contract or any other document that is filed as an exhibit to the registration statement are not necessarily complete, and each such statement is qualified in all respects by reference to the full text of such contract or other document filed as an exhibit to the registration statement. The SEC also maintains an Internet website that contains reports, proxy statements and other information about registrants, like us, that file electronically with the SEC. The address of that site is www.sec.gov.

Upon the effectiveness of the registration statement, we will be subject to the informational requirements of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and, in accordance with the Exchange Act, will file reports, proxy and information statements and other information with the SEC. Such annual, quarterly and special reports, proxy and information statements and other information can be inspected and copied at the locations set forth above. We intend to make this information available on the investor relations section of our website, which is located at www.cyteir.com. Information on, or accessible through, our website is not part of this prospectus.

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Index to consolidated financial statements

Consolidated financial statements for the years ended December 31, 2020 and 2019:

Report of Independent Registered Public Accounting Firm	F-2
Consolidated Balance Sheets	F-3
Consolidated Statements of Operations	F-4
Consolidated Statements of Redeemable Convertible Preferred Stock and Stockholders’ Deficit	F-5
Consolidated Statements of Cash Flows	F-6
Notes to Consolidated Financial Statements	F-7

F-1

Report of independent registered public accounting firm

To the Shareholders and the Board of Directors of Cyteir Therapeutics, Inc.

Opinion on the financial statements

We have audited the accompanying consolidated balance sheets of Cyteir Therapeutics, Inc. (the Company) as of December 31, 2020 and 2019, the related consolidated statements of operations, redeemable convertible preferred stock and stockholders’ deficit, and cash flows for the years then ended, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2020 and 2019, and the results of its operations and its cash flows for the years then ended in conformity with U.S. generally accepted accounting principles.

Basis for opinion

These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB and in accordance with auditing standards generally accepted in the United States of America. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

/s/ Ernst & Young LLP

We have served as the Company’s auditor since 2019.

Boston, Massachusetts

March 26, 2021

F-2

CYTEIR THERAPEUTICS, INC.

Consolidated balance sheets

	Years ended December 31,
(in thousands, except share and per share amounts)	2020			2019
Assets
Current assets:
Cash and cash equivalents	$	10,938		$	29,012
Prepaid expenses and other current assets		1,193			1,425
Total current assets		12,131			30,437
Property and equipment, net		1,287			788
Other assets		317			144
Total assets	$	13,735		$	31,369
Liabilities, redeemable convertible preferred stock and stockholders’ deficit
Current liabilities:
Accounts payable	$	1,689		$	602
Accrued expenses and other current liabilities		1,448			1,370
Total current liabilities		3,137			1,972
Deferred rent, net of current portion		452			322
Other long term liabilities		766			—
Total liabilities		4,355			2,294
Commitments and contingencies (Note 12)
Series A redeemable convertible preferred stock, 5,817,996 shares authorized, issued, and outstanding as of December 31, 2020 and 2019; liquidation preference of $5,818 as of December 31, 2020		5,696			5,696
Series B redeemable convertible preferred stock, 71,199,999 shares authorized as of December 31, 2020 and 2019; 55,200,000 shares issued and outstanding as of December 31, 2020 and 2019; liquidation preference of $55,200 as of December 31, 2020		51,715			51,715
Stockholders’ deficit:
Common stock, $0.001 par value: 100,000,000 shares authorized as of December 31, 2020 and 2019; 9,269,749 and 4,816,408 shares issued as of December 31, 2020 and 2019, respectively; 6,968,483 and 4,816,408 shares outstanding as of December 31, 2020 and 2019, respectively		7			5
Additional paid-in capital		1,889			763
Accumulated deficit		(49,927	)		(29,104	)
Total stockholders’ deficit		(48,031	)		(28,336	)
Total liabilities, redeemable convertible preferred stock and stockholders’ deficit	$	13,735		$	31,369

See accompanying notes to consolidated financial statements.

F-3

CYTEIR THERAPEUTICS, INC.

Consolidated statements of operations

	Years ended December 31,
(in thousands, except share and per share amounts)	2020			2019
Grant revenue	$	—		$	8
Operating expenses:
Research and development		16,765			12,768
General and administrative		4,178			3,345
Total operating expenses		20,943			16,113
Loss from operations		(20,943	)		(16,105	)
Total other income:
Other income		120			246
Change in preferred stock tranche obligation		—			815
Total other income		120			1,061
Net loss	$	(20,823	)	$	(15,044	)
Net loss attributable to common stockholders—basic and diluted	$	(20,823	)	$	(15,044	)
Net loss per share—basic and diluted	$	(3.99	)	$	(3.42	)
Weighted-average common stock outstanding—basic and diluted		5,217,910			4,397,374

See accompanying notes to consolidated financial statements.

F-4

CYTEIR THERAPEUTICS, INC.

Consolidated statements of redeemable convertible preferred stock and stockholders’ deficit

	Redeemable convertible preferred stock												Additional paid-in capital		Accumulated deficit
	Series A				Series B				Common stock									Total stockholders’ deficit
(in thousands, except share and per share amounts)	Shares		Amount		Shares		Amount		Shares		Amount
Balance at December 31, 2018		5,817,996	$	5,696		17,500,000	$	15,093		3,895,430	$	4	$	249	$	(14,060	)	$	(13,807	)
Exercise of common stock options		—		—		—		—		920,978		1		267		—			268
Issuance of Series B redeemable convertible preferred stock, net of issuance costs of $1,078		—		—		37,700,000		36,622		—		—		—		—			—
Stock-based compensation expense		—		—		—		—		—		—		247		—			247
Net loss		—		—		—		—		—		—		—		(15,044	)		(15,044	)
Balance at December 31, 2019		5,817,996	$	5,696		55,200,000	$	51,715		4,816,408	$	5	$	763	$	(29,104	)	$	(28,336	)
Exercise of common stock options		—		—		—		—		2,130,268		2		651		—			653
Vesting of early exercised options		—		—		—		—		21,807		—		8		—			8
Stock-based compensation expense		—		—		—		—		—		—		467		—			467
Net loss		—		—		—		—		—		—		—		(20,823	)		(20,823	)
Balance at December 31, 2020		5,817,996	$	5,696		55,200,000	$	51,715		6,968,483	$	7	$	1,889	$	(49,927	)	$	(48,031	)

See accompanying notes to consolidated financial statements

F-5

CYTEIR THERAPEUTICS, INC.

Consolidated statements of cash flows

	Years ended December 31,
(in thousands)	2020			2019
Cash flows from operating activities:
Net loss	$	(20,823	)	$	(15,044	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation expense		351			215
Stock-based compensation		467			247
Change in fair value of preferred stock tranche obligation		—			(815	)
Changes in operating assets and liabilities:
Prepaid expenses and other current assets		231			(1,287	)
Accounts payable		1,027			(884	)
Accrued expenses and other current liabilities		78			108
Deferred rent		130			(97	)
Net cash used in operating activities		(18,539	)		(17,557	)
Cash flows from investing activities:
Purchases of property and equipment		(850	)		(133	)
Net cash used in investing activities		(850	)		(133	)
Cash flows from financing activities:
Proceeds from issuance of preferred stock , net of issuance costs		—			36,622
Proceeds from the early exercise of stock options		766			—
Proceeds from exercise of stock options		661			268
Net cash provided by financing activities		1,427			36,890
Net (decrease) increase in cash, cash equivalents, and restricted cash		(17,962	)		19,200
Cash, cash equivalents and restricted cash at beginning of period		29,156			9,956
Cash, cash equivalents and restricted cash at end of period	$	11,194		$	29,156
Supplemental disclosure of cash flows
Deferred financing costs in accounts payable	$	61		$	—

The following table provides a reconciliation of the cash, cash equivalents, and restricted cash balances as of each of the dates shown below:

	Years Ended December 31,
	2020		2019
Cash and cash equivalents	$	10,938	$	29,012
Restricted cash (included in other assets)		256		144
Total cash, cash equivalents, and restricted cash	$	11,194	$	29,156

See accompanying notes to consolidated financial statements.

F-6

CYTEIR THERAPEUTICS, INC.

Notes to consolidated financial statements

1. Nature of the business

Cyteir Therapeutics, Inc., (the “Company”) is a clinical-stage biotechnology company focused on developing and commercializing the next generation of precision oncology medicines that inhibit DNA damage repair and cause cancer cell death through a therapeutic strategy known as synthetic lethality. The Company’s lead program, CYT-0851, as well as its next generation drug candidate, CYT-1853, exploit a novel gain-of-function synthetically lethal relationship between overexpression of a family of DNA damaging genes called cytidine deaminases, and functional inhibition of homologous recombination, a DNA repair pathway critical for the survival of some cancers. The Company is using its expertise in DNA Damage Response biology and a disciplined approach to select targets for other novel, differentiated programs with the aim of building a patient-centric portfolio of effective cancer therapies.

The Company was formed as a Delaware corporation on June 4, 2012, pursuant to the General Corporation Law of the State of Delaware. The Company has a principal office in Lexington, Massachusetts.

Liquidity

The Company has incurred negative cash flows since inception and has funded its operations primarily with proceeds from the sale of redeemable convertible preferred stock and from United States government grants. As of December 31, 2020, the Company had cash and cash equivalents of $10.9 million and an accumulated deficit of $49.9 million. The Company expects its operating losses and negative operating cash flows to continue into the foreseeable future as it continues to expand its research and development efforts.

The Company expects that its cash and cash equivalents as of December 31, 2020, together with the $80.0 million raised in the Series C preferred stock financing in February 2021, will be sufficient to fund its operating expenses and capital expenditure requirements for at least twelve months from the date these consolidated financial statements are available to be issued.

The Company will need additional funding to support its planned operating activities. There can be no assurances, however, that the current operating plan will be achieved or that additional funding will be available on terms acceptable to the Company, or at all. If the Company is unable to obtain sufficient funding, it could be required to delay its development efforts, limit activities and reduce research and development costs, which could adversely affect its business prospects.

COVID-19 considerations

The development of the Company’s product candidates could be disrupted and materially adversely affected in by a pandemic, epidemic or outbreak of an infectious disease, such as the ongoing COVID-19 pandemic. The ongoing COVID-19 pandemic and the measures taken by the governments of countries affected by it could disrupt the supply chain and the manufacture or shipment of both drug substance and finished drug product for the Company’s product candidates for preclinical testing or clinical trials, cause diversion of healthcare resources away from the conduct of preclinical and clinical trial matters to focus on pandemic concerns, limit travel in a manner that interrupts key trial activities, such as trial site initiations and monitoring, delay regulatory filings with regulatory agencies in affected areas or adversely affect the Company’s ability to obtain regulatory approvals. These disruptions could also affect other facets of the Company’s business, including, but not limited to, the Company’s ability to recruit employees from outside of the United States, the ability of the Company’s CROs to conduct clinical trials and preclinical studies in countries outside of the United States, the Company’s ability to import materials from outside of the United States, including raw materials required to

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manufacture its drug candidates, the Company’s ability to export materials to its CROs and other third-parties located outside of the United States, the Company’s ability to identify suitable clinical sites or open those sites for enrollment due to competing business needs, the Company’s ability to enroll patients due to their fear of coming into medical facilities and their perceived risk of becoming infected at such facilities, and the Company’s ability to monitor the clinical data generated at its clinical sites, required for completion of clinical trials.

The COVID-19 pandemic and mitigation measures also may have an adverse impact on global economic conditions, which could adversely impact the Company’s business, financial condition or results of operations. Additionally, the COVID-19 pandemic has resulted in significant financial market volatility and uncertainty. A continuation or worsening of the levels of market disruption and volatility as a result of the COVID-19 pandemic could have an adverse effect on the Company’s ability to access capital and on the market price of its common stock. The Company cannot presently predict the scope and severity of any potential business shutdowns or disruptions, but if the Company or any of the third parties on whom it relies on or with whom it conducts business, were to experience shutdowns or other business disruptions, the Company’s ability to conduct business in the manner and on the timelines presently planned could be materially and adversely impacted.

2. Summary of significant accounting policies

Basis of presentation and consolidation

The accompanying consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”). In December 2019, the company formed a wholly-owned subsidiary, Cyteir Securities Corporation, which was incorporated as a Massachusetts Security Corporation. The consolidated financial statements include the Company’s accounts and those of its wholly-owned subsidiary. All intercompany accounts, transactions and balances have been eliminated in consolidation.

Use of estimates

The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of expenses during the reporting period. Changes in estimates and assumptions are reflected in reported results in the period in which they become known. Actual results could differ from those estimates.

Segment information

Operating segments are defined as components of an enterprise for which separate and discrete information is available for evaluation by the chief operating decision-maker in deciding how to allocate resources and assess performance. The Company has one operating segment. The Company’s focus is the research and development of small molecule therapeutics that target DNA repair in cancer and autoimmune cells. The Company’s chief operating decision maker, its Chief Executive Officer, manages the Company’s operations on a consolidated basis for the purpose of allocating resources. All of the Company’s long-lived assets are held in the United States.

Cash and cash equivalents

The Company considers all highly liquid investments purchased with original maturities of 90 days or less at acquisition to be cash equivalents. Cash and cash equivalents include standard checking accounts and amounts held in money market funds.

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Restricted cash

Cash accounts with any type of restriction are classified as restricted cash. The Company has restricted cash deposits with a bank, which serve as collateral for a letter of credit issued to the landlord of the Company’s leased facility for a security deposit. The Company classified this amount as restricted cash in the accompanying consolidated balance sheets within non-current assets as of December 31, 2020 and 2019.

Concentration of credit risk and off-balance sheet risk

Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash, cash equivalents, and restricted cash. The Company may maintain deposits in federally insured financial institutions and limits its exposure to cash risk by keeping amounts in each institution under the federally insured limits and by placing its cash with high credit quality financial institutions, further the Company has not experienced any losses on these deposits. The Company’s investment policy includes guidelines on the quality of the institutions and financial instruments and defines allowable investments that the Company believes minimize its exposure to concentration of credit risk. The Company has no financial instruments with off-balance-sheet risk of loss and has not experienced any losses on such accounts.

The Company is dependent on third-party contract research organizations (“CROs”) and contract manufacturing organizations (“CMOs”) with whom they do business. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements of active pharmaceutical ingredients and formulated drugs in order to perform research and development activities in its programs. The Company also relies on a limited number of third-party contract research organizations to perform research and development activities on its behalf. These programs could be adversely affected by significant interruption from these providers.

Comprehensive loss

Comprehensive loss includes net loss as well as other changes in stockholders’ deficit that result from transactions and economic events other than those with stockholders. For the years ended December 31, 2020 and December 31, 2019, there was no difference between net loss and comprehensive loss.

Property and equipment, net

Property and equipment are stated at cost, less accumulated depreciation. Costs of major additions and betterments are capitalized. Maintenance and repairs which do not improve or extend the life of the respective assets are charged to expense as incurred. Depreciation is calculated using the straight-line method over the estimated useful lives of the assets, which range from five to seven years. Leasehold improvements are amortized over the shorter of the lease term or the estimated useful life of the related asset. When an item is sold or retired, the costs and related accumulated depreciation are eliminated, and the resulting gain or loss, if any, is credited or charged to the consolidated statements of operations. Property and equipment to be disposed of are carried at fair value less costs to sell. The estimated useful lives of the Company’s property and equipment are as follows:

	Estimated useful life (in years)
Laboratory equipment and computer equipment	5 years
Furniture	5-7 years
Leasehold improvements	Lesser of asset useful life or lease term

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Impairment of long-lived assets

The Company accounts for long-lived assets in accordance with ASC Topic 360, Property, Plant, and Equipment (“ASC 360”). ASC 360 requires companies to: (i) recognize an impairment loss only if the carrying amount of a long-lived asset is not recoverable based on its undiscounted future cash flows and (ii) measure an impairment loss as the difference between the carrying amount and the fair value of the asset.

The Company tests long-lived assets to be held and used, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying amount of assets or asset groups may not be fully recoverable. Determination of recoverability is based on an estimate of undiscounted future cash flows resulting from the use of the asset and its eventual disposition. In the event that such cash flows are not expected to be sufficient to recover the carrying amount of the assets, the assets are written down to their fair values. The Company has not recognized any impairment losses during the years ended December 31, 2020 and 2019.

Fair value measurements

ASC Topic 820, Fair Value Measurement (“ASC 820”), establishes a fair value hierarchy for instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and the Company’s own assumptions (unobservable inputs). Observable inputs are inputs that market participants would use in pricing the asset or liability based on market data obtained from sources independent of the Company. Unobservable inputs are inputs that reflect the Company’s assumptions about the inputs that market participants would use in pricing the asset or liability and are developed based on the best information available in the circumstances.

ASC 820 identifies fair value as the exchange price, or exit price, representing the amount that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants. As a basis for considering market participant assumptions in fair value measurements, ASC 820 establishes a three-tier fair value hierarchy that distinguishes among the following:

Level 1—Quoted prices in active markets for identical assets or liabilities.

Level 2—Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data.

Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to determining the fair value of the assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques.

To the extent that the valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement. The Company has no assets or liabilities classified as Level 3 on its consolidated balance sheets as of December 31, 2020 and 2019.

Financial instruments consist of cash and cash equivalents, restricted cash and accrued expenses. These financial instruments are stated at their respective historical carrying amounts, which approximate fair value due to their short-term nature.

F-10

Deferred financing costs

The Company capitalizes certain legal, professional accounting and other third-party fees that are directly associated with in-process equity financings as deferred financing costs until such financings are closed. After consummation of the equity financing, these costs are presented in the consolidated balance sheets as a direct reduction from the carrying amount of the respective equity instrument issued. Should an in-process equity financing be abandoned, the deferred offering costs will be expensed immediately as a charge to operating expenses in the consolidated statements of operations. As of December 31, 2020, the Company recorded deferred financing costs of $0.1 million, presented within other assets on the consolidated balance sheets. No amounts were recorded as of December 31, 2019.

Revenue recognition

No revenue was recognized during the year ended December 31, 2020. All revenue recognized during the year ended December 31, 2019 relates to grants from the National Institutes of Health (“NIH”). In 2015, the Company received grants from the NIH for a total of $0.2 million to perform research and development activities, specifically to develop therapeutics that target RAD51 to treat Leukemia and Lymphoma. In 2017, the Company received an award of $1.0 million for Phase 2 of the same project. The project period for Phase 2 expired in 2019.

The Company adopted ASC 606, Revenue from Contracts with Customers (“ASC 606”), on January 1, 2019 using a modified retrospective adoption approach, which resulted in no transition adjustment and impact

Under ASC 606, the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that are within the scope of ASC 606, the Company performs the following five steps: (i) identify the contract(s) with a customer, (ii) identify the performance obligations in the contract, (iii) determine the transaction price, (iv) allocate the transaction price to the performance obligations in the contract, and (v) recognize revenue when (or as) the entity satisfies a performance obligation. A performance obligation is a promise in a contract to transfer a distinct good or service to the customer. Once performance obligations are identified, the Company then recognizes as revenue the amount of the transaction price that the Company allocated to the respective performance obligation when (or as) each performance obligation is satisfied, either at a point in time or over time. If the performance obligation is satisfied over time, the Company recognizes revenue based on the use of an input method.

The Company identifies the goods or services promised within each agreement and assesses whether each promised good or service is distinct for the purpose of identifying the performance obligations in the contract. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. Promised goods and services are considered distinct provided that: (i) the customer can benefit from the good or service either on its own or together with other resources that are readily available to the customer and (ii) the entity’s promise to transfer the good or service to the customer is separately identifiable from other promises in the contract. If a promised good or service is not distinct, an entity is required to combine that promised good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct.

The allocation of the transaction price to the performance obligations in proportion to their standalone selling prices is determined at contract inception. If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes

F-11

the unconstrained amount of estimated variable consideration in the transaction price. The amount included in the transaction price is the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment.

Deferred rent

Deferred rent consists of rent escalation payment terms, tenant improvement allowances, and other incentives received from landlords related to the Company’s operating leases. Rent escalation represents the difference between actual operating lease payments due and straight-line rent expense, which is recorded by the Company over the term of the lease. Tenant improvement allowances and other incentives are recorded as deferred rent and amortized as a reduction of periodic rent expense, over the term of the lease.     

Research and development costs

Research and development costs are charged to expense as incurred. Research and development expenses are comprised of costs incurred in performing research and development activities, including personnel-related costs, stock-based compensation, facilities, research-related overhead, clinical trial costs, contracted services, research-related manufacturing, license fees and other external costs. The Company accounts for nonrefundable advance payments for goods and services that will be used in future research and development activities as expenses when the services have been performed or when the goods have been received.

Accrued research and development expenses

The Company has entered into various research and development contracts. The payments under these contracts are recorded as research and development expenses as incurred. The Company records accrued liabilities for estimated ongoing research and development costs. When evaluating the adequacy of the accrued liabilities, the Company analyzes the progress of the research and development activities, including the phase or completion of events, invoices received and contracted costs. Significant judgements and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the Company’s estimates. The Company’s historical accrual estimates have not been materially different from the actual costs.

Patent costs

All patent-related costs incurred in connection with filing and prosecuting patent applications such as direct application fees, and legal and consulting expenses are expensed as incurred due to the uncertainty about the recovery of the expenditure. Patent-related costs are classified as general and administrative expenses within the Company’s consolidated statements of operations.

Redeemable convertible preferred stock

The Company has classified redeemable convertible preferred stock (“preferred stock”) as temporary equity in the accompanying consolidated balance sheets due to terms that allow for redemption of the shares upon certain events that are outside of the Company’s control. The Company does not accrete the carrying values of the preferred stock to the redemption values since the occurrence of these events was not considered probable as of December 31, 2020 and 2019. Subsequent adjustments of the carrying values to the ultimate redemption values will be made only when it becomes probable that these events will occur.

F-12

Stock-based compensation

The Company accounts for all share-based payment awards granted to employees and non-employees as stock-based compensation expense at fair value. The Company’s share-based payments include stock options and grants of common stock, including common stock subject to vesting. The measurement date for employee awards is the date of grant, and stock-based compensation costs are recognized as expense over the employees’ requisite service period, which is the vesting period, on a straight-line basis. Prior to the adoption of Accounting Standards Update (“ASU”) No. 2018-07, Compensation—Stock Compensation (Topic 718): Improvements to Nonemployee Share-Based Payment Accounting (“ASU No. 2018-07”) on January 1, 2020, the measurement date for non-employee awards was generally the date the services were completed, resulting in financial reporting period adjustments to stock-based compensation during the vesting terms for changes in the fair value of the awards. Since the adoption of ASU 2018-07, the measurement date for non-employee awards is the date of grant without changes in the fair value of the award. There was no material impact as a result of adopting this new standard. Stock-based compensation costs for non-employees are recognized as expense over the vesting period on a straight-line basis. Stock-based compensation expense is classified in the accompanying consolidated statements of operations based on the function to which the related services are provided. Forfeitures are recorded as they occur.

The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option-pricing model. The Company has historically been a private company and lacks company-specific historical and implied volatility information. Therefore, it estimates its expected stock volatility based on the historical volatility of a publicly traded set of representative companies and expects to continue to do so until such time as it has adequate historical data regarding the volatility of its own traded stock price. The expected term of the Company’s stock options has been determined utilizing the “simplified” method for awards that qualify as “plain-vanilla” options. The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant of the award for time periods approximately equal to the expected term of the award. Expected dividend yield is based on the fact that the Company has never paid cash dividends on common stock and does not expect to pay any cash dividends in the foreseeable future.

Net loss per share

Basic net loss per share is computed by dividing net loss by the weighted-average number of common shares outstanding during the period. Diluted net loss per share is computed using the weighted-average

number of common shares outstanding during the period and, if dilutive, the weighted-average number of potential shares of common stock. Net loss per share attributable to common stockholders is calculated using the two-class method, which is an earnings allocation formula that determines net loss per share for the holders of the Company’s common shares and participating securities. The Company’s preferred stock contains participation rights in any dividend paid by the Company and is deemed to be a participating security. Net loss attributable to common stockholders and participating preferred shares are allocated to each share on an as-converted basis as if all of the earnings for the period had been distributed. The participating securities do not include a contractual obligation to share in losses of the Company and are not included in the calculation of net loss per share in the periods in which a net loss is recorded.

Diluted net loss per share is computed using the more dilutive of (a) the two-class method or (b) the if-converted method. The Company allocates earnings first to preferred stockholders based on dividend rights and then to common and preferred stockholders based on ownership interests. The weighted-average number of common shares included in the computation of diluted net loss gives effect to all potentially dilutive common equivalent shares, including outstanding stock options and preferred stock.

F-13

Common stock equivalent shares are excluded from the computation of diluted net loss per share if their effect is antidilutive. In periods in which the Company reports a net loss attributable to common stockholders, diluted net loss per share attributable to common stockholders generally the same as basic net loss per share attributable to common stockholders since dilutive common shares are not assumed to have been issued if their effect is anti-dilutive. The Company reported a net loss attributable to common stockholders for the years ended December 31, 2020 and 2019.

Income taxes

The Company accounts for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in the financial statements or the Company’s tax returns. Under this method, deferred tax assets and liabilities are determined based on the differences between the consolidated financial statements and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. Changes in deferred tax assets and liabilities are recorded in the provision for income taxes. The Company assesses the likelihood that its deferred tax assets will be recovered from future taxable income and, to the extent it believes, based upon the weight of available evidence, that it is more likely than not that all or a portion of the deferred tax assets will not be realized, a valuation allowance is established.

The Company accounts for uncertain tax positions recognized in the consolidated financial statements by prescribing a “more likely than not” threshold for financial statement recognition and measurement of a tax position taken or expected to be taken in a tax return. There are no unrecognized tax benefits included in the Company’s consolidated balance sheet as of December 31, 2020 and 2019. The Company’s policy is to recognize interest and penalties related to income tax matters in income tax expense. The Company has not recognized interest or penalties in its Statements of Operations since inception.

Recently issued accounting pronouncements

In August 2016, the FASB issued ASU No. 2016-15, Classification of Certain Cash Receipts and Cash Payments (ASU 2016-15), which includes amendments that clarify how certain cash receipts and cash payments are presented in the consolidated statements of cash flows. The guidance also clarifies when an entity should separate cash receipts and cash payments and classify them into more than one class of cash flows. ASU 2016-15 is effective for non-public entities for annual periods beginning after December 15, 2018. The Company adopted this ASU on January 1, 2019 and the impact was not material to the consolidated financial statements.

Recently issued accounting pronouncements not yet adopted

In February 2016, the FASB issued ASU 2016-02, Leases (Topic 842) to increase transparency and comparability among organizations by recognizing lease assets and lease liabilities on the consolidated balance sheets for all leases and disclosing key information about leasing arrangements. This ASU was originally proposed to be effective for annual reporting periods after December 15, 2019, however, in July 2019, the FASB delayed the effective date to January 2021 and ASU 2020-05 delayed the effective date to January 2022. The Company is currently evaluating the impact that this standard will have on its consolidated financial statements and related disclosures.

In August 2018, the FASB issued ASU No. 2018-13, Disclosure Framework – Changes to the Disclosure Requirements for Fair Value Measurement, which modifies certain disclosure requirements on fair value measurements. The amendments on changes in unrealized gains and losses, the range and weighted average of significant unobservable inputs used to develop Level 3 fair value measurements and the narrative description of measurement uncertainty should be applied prospectively for only the most recent interim or annual period presented in the initial fiscal year of adoption. All other amendments should be applied retrospectively to all

F-14

periods presented upon their effective date. ASU 2018-13 is effective for fiscal years beginning after December 15, 2020 for nonpublic entities. The Company does not anticipate a material impact to its disclosures as a result of the adoption of ASU 2018-13.

In December 2019, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update No. 2019-12 (ASU 2019-12) Simplifying the Accounting for Income Tax. The standard contains several provisions that reduce financial statement complexity including removing the exception to the incremental approach for intra-period tax expense allocation when a company has a loss from continuing operations and income from other items not included in continuing operations. The new guidance is effective for the year beginning January 1, 2022 with optional adoption prior to the effective date. The Company does not expect that the new standard will have a material impact to the Company’s consolidated financial statements.

3. Fair value measurement

The following tables present information about the Company’s financial assets and liabilities measured at fair value on a recurring basis (in thousands):

			December 31, 2020
Description	Total		Quoted prices in active markets for identical assets (level 1)		Significant other observable inputs (level 2)		Significant other observable inputs (level 3)
Assets:
Cash equivalents	$	10,938	$	10,938	$	—	$	—
Total assets	$	10,938	$	10,938	$	—	$	—

			December 31, 2019
Description	Total		Quoted prices in active markets for identical assets (level 1)		Significant other observable inputs (level 2)		Significant other observable inputs (level 3)
Assets:
Cash equivalents	$	29,012	$	29,012	$	—	$	—
Total assets	$	29,012	$	29,012	$	—	$	—

During the years ended December 31, 2020 and 2019, there were no transfers between levels. The fair values of the Company’s cash equivalents, consisting of its standard checking accounts and money market funds, are based on quoted market prices in active markets without any valuation adjustment.

The Company uses the carrying amounts of its restricted cash, prepaid expenses and other current assets, accounts payable and accrued expenses to approximate their fair value due to the short-term nature of these amounts.

F-15

Preferred stock tranche obligation

The preferred stock tranche obligation relates to the Company’s obligation to issue, and investors’ obligation to purchase, additional shares of our Series B redeemable convertible preferred stock (“Series B Preferred Stock”) following the initial closing of our Series B financing. The Company has determined that the obligation to issue additional shares of preferred stock is a freestanding instrument recorded at fair value. In July 2019, upon the issuance of the final tranche of Series B Preferred Stock”) in exchange for $17.5 million, the preferred stock tranche obligation was satisfied. As the shares were determined to be issued at fair value, there was no value of the preferred stock tranche obligation upon settlement. The preferred stock tranche obligation was reduced to zero as of the settlement date.

The following table provides a roll forward of the aggregate fair value of the Company’s preferred stock tranche liability (in thousands):

Balance at December 31, 2018	$	815
Change in fair value of preferred stock tranche obligation		(815	)
Balance at December 31, 2019	$	—

4. Prepaid expenses and other current assets

Prepaid expenses and other current assets consisted of the following (in thousands):

	December 31,
	2020		2019
Prepaid research and development expenses	$	871	$	1,105
Payroll tax credit		63		164
Prepaid other		259		155
Total	$	1,193	$	1,424

5. Property and equipment, net

Property and equipment, net consisted of the following (in thousands):

	December 31,
	2020			2019
Laboratory and computer equipment	$	694		$	492
Leasehold improvements		1,268			621
Total property and equipment		1,962			1,113
Less: accumulated depreciation		(675	)		(325	)
Property and equipment, net	$	1,287		$	788

Depreciation and amortization expense related to property and equipment for the years ended December 31, 2020 and December 31, 2019 was $0.4 million and $0.2 million, respectively.

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6. Accrued expenses and other current liabilities

Accrued expenses and other current liabilities consisted of the following (in thousands):

	December 31,
	2020		2019
Accrued research and development expenses	$	193	$	407
Accrued bonuses		854		533
Accrued other		401		430
Total accrued expenses and other current liabilities	$	1,448	$	1,370

7. Redeemable convertible preferred stock

In October 2015, the Company issued 5,817,996 shares of Series A redeemable convertible preferred stock (“Series A Preferred Stock”) at a price of $1.00 per share.

In January 2018, the Company issued 2,677,521 shares of Series B Preferred Stock at a price of $1.00 per share and agreed to issue up to an additional 32,322,479 shares at a price of $1.00 per share upon the achievement of certain specified milestones. In March 2018 and July 2018, the Company issued an additional 3,155,805 and 11,666,667 shares of Series B Preferred Stock, respectively, in accordance with the terms of the agreement. In July 2019, the Company issued the final 17,500,007 shares of Series B Preferred Stock in accordance with the terms of the agreement.

The issuance of 32,322,479 additional shares of Series B Preferred Stock based on the achievement of defined milestones pursuant to which the investors are required to purchase, and the Company to sell, is referred to herein as the preferred stock tranche obligation. The Company concluded that the preferred stock tranche obligation met the definition of a freestanding financial instrument, as the obligation was legally detachable and separately exercisable from the Series B Preferred Stock. Therefore, the Company allocated the net proceeds between the preferred stock tranche obligation and the Series B Preferred Stock. Since the Series B Preferred Stock underlying the preferred stock tranche obligation was contingently redeemable upon the occurrence of a deemed liquidation event, the preferred stock tranche obligation was classified as a liability under ASC Topic 480 Distinguishing Liabilities from Equity and was initially recorded at fair value. The preferred stock tranche obligation was then remeasured at fair value at each reporting period and settlement date. This obligation was fully satisfied in July 2019 when the third and final tranche of the Series B Preferred Stock issuance closed.

In September 2019, the Company entered into a separate agreement and issued 20,200,000 shares of Series B Preferred Stock at a purchase price of $1.00 per share.

Upon issuance of each class of convertible preferred stock, the Company assessed the embedded conversion and liquidation features of the shares and determined that such features did not require the Company to separately account for these features. The Company also concluded that no beneficial conversion feature existed on the issuance date of each class of convertible preferred stock.

F-17

Preferred stock consisted of the following as of the dates presented (in thousands, except share amounts):

	December 31, 2020
	Preferred stock authorized		Preferred stock issued and outstanding		Carrying value		Liquidation value		Common stock issuable upon conversion
Series A Preferred Stock		5,817,996		5,817,996	$	5,696	$	5,696		5,817,996
Series B Preferred Stock		71,199,999		55,200,000		51,715		51,715		55,200,000
Total		77,017,995		61,017,996	$	57,411	$	57,411		61,017,996
	December 31, 2019
	Preferred stock authorized		Preferred stock issued and outstanding		Carrying value		Liquidation value		Common stock issuable upon conversion
Series A Preferred Stock		5,817,996		5,817,996	$	5,696	$	5,696		5,817,996
Series B Preferred Stock		71,199,999		55,200,000		51,715		51,715		55,200,000
Total		77,017,995		61,017,996	$	57,411	$	57,411		61,017,996

Significant terms of the Series A Preferred Stock and Series B Preferred Stock (collectively, “Preferred Stock”) are as follows:

Voting

The holder of each share of Preferred Stock is entitled to one vote for each share of common stock into which it would convert and to vote with the common stock on all matters. As long as a minimum number of Series A Preferred Stock and Series B Preferred Stock is outstanding, the holders of the Series A Preferred Stock and Series B Preferred Stock are entitled to elect three directors and the approval of certain actions requires a majority of the Preferred Stockholders.

Conversion

As of December 31, 2020, the shares of Preferred Stock are convertible into shares of common stock, at the conversion price in effect at the time of such conversion, which is initially one-for-one subject to adjustment for certain potential non-dilutive transactions. The conversion can be initiated by the holder at any time or is mandatory (a) at any time upon the written consent of the holders of a majority of the outstanding shares of the Preferred Stock or (b) immediately upon the closing of a qualified public offering of gross proceeds to the Company of at least $50,000,000. In the event that any holder of shares of Series B Preferred Stock does not purchase the full amount of such holder’s preferred stock tranche obligation, then each share of Series B Preferred Stock held by such holder shall automatically be converted into shares of common stock at a ratio of 1/10th of the applicable conversion ratio. As all tranche obligations were completed as of July 2019, this conversion feature expired unexercised.

Dividends

The holders of the Preferred Stock are entitled to receive dividends at the rate of 8% of the applicable original issue price per annum, as potentially adjusted for certain non-dilutive transactions. Dividends shall accrue whether or not declared, shall not be cumulative or compounded and shall be payable only when, as and if declared by the Board of Directors (the “Board”) and in preference and in priority to any dividends on common stock. There have been no dividends declared by the Board as of December 31, 2020.

F-18

Liquidation preference

In the event of any liquidation, dissolution, or winding up of the Company (“Liquidation Event”), the holders of Preferred Stock are entitled to receive prior and in preference to the holders of common stock, an amount equal to an amount per share equal to the greater of the original issue price, as potentially adjusted for certain non-dilutive transactions, plus all declared and unpaid dividends on the Preferred Stock or the price per share that would be received if the Preferred Stock were converted to common stock. If the assets and funds available to be distributed to all holders of Preferred Stock are insufficient to permit the payment, in full, of any of the liquidation preferences, then the entire assets and funds legally available for distribution to holders of the Preferred Stock shall be distributed ratably among the holders of Preferred Stock, acting as a single class, at the time outstanding, ratably in proportion to the full amounts to which they would otherwise be respectively entitled.    

After the payment of the full liquidation preference of the Preferred Stock as set forth above, the remaining assets of the Company legally available for distribution in such Liquidation event shall be distributed ratably to the holders of shares of common stock.

Redemption

The Company has determined that all series of preferred stock are redeemable, based on the Certificate of Incorporation that states upon the occurrence of a deemed liquidation event, the holders of preferred stock are entitled to receive cash or other assets.

8. Common stock

The voting, dividend and liquidation rights of the holders of the Company’s common stock are subject to and qualified by the rights, powers and preferences of the holders of the preferred stock as set forth above.

The holders of the common stock are entitled to one vote for each share of common stock held at all meetings of stockholders (and written actions in lieu of meetings), and there are not any cumulative voting rights. The number of authorized shares of common stock may be increased or decreased by the affirmative vote of the holders of shares of capital stock of the Company; however, the issuance of common stock may be subject to the vote of the holders of one or more series of preferred stock that may be required by terms of the Certificate of Incorporation.

As of December 31, 2020, and 2019, the Company has reserved the following shares of common stock for the potential conversion of outstanding preferred stock and exercise of stock options:

	December 31,
	2020		2019
Preferred Stock, as converted		61,017,996		61,017,996
Options to purchase common stock		4,407,697		4,075,716
Remaining shares reserved for future issuance		504,558		5,289,880
Total		65,930,251		70,383,592

9. Stock-based compensation

2012 stock incentive plan

The Company adopted the 2012 Stock Incentive Plan (the “2012 Plan”) in February 2016 pursuant to which the Company can issue incentive stock options, non-statutory stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards and other stock awards. Recipients of stock options or stock appreciate rights shall be eligible to purchase shares of the Company’s common stock at an exercise price equal

F-19

to the estimated fair market value of such stock on the date of grant. The exercise price may be less than fair market value if the stock award is granted pursuant to an assumption or substitution for another stock award in the event of a merger or sale of the Company. The maximum term of options granted under the 2012 Plan is ten years, and stock options typically vest over a four year period. The Board may assign vesting terms to the stock options grants as deemed appropriate. The Company also has the right of refusal to purchase any proposed disposition of shares issued under the 2012 Plan. The 2012 Plan allows for early exercise of all stock option grants if authorized by the Board at the time of grant. The shares of common stock issued from the early exercise of stock options are restricted and vest over time. The Company has the option to repurchase any unvested shares at the original purchase price upon any voluntary or involuntary termination. At the discretion of the Board, unvested shares held by employees may accelerate vesting in the event of a change of control of the Company unless assumed or substituted by the acquirer or surviving entity. The 2012 Plan has been subsequently amended and provides for the issuance of up to 10,360,724 shares of common stock as of December 31, 2020, of which 504,558 shares of common stock remain available for future grant under the 2012 Plan.

Early exercise of unvested stock options

Shares purchased by employees pursuant to the early exercise of stock options are not deemed, for accounting purposes, to be outstanding shares until those shares vest according to their respective vesting schedules. Cash received from employee exercises of unvested options is included in long-term liabilities on the consolidated balance sheets. Amounts recorded are reclassified to common stock and additional paid-in capital as the shares vest. As of December 31, 2020, there were 2,301,266 unvested shares related to early exercises of stock options. There were no early exercises during the year ended December 31, 2019.

Stock option valuation

The assumptions that the Company used in the Black Scholes option-pricing model to determine the grant date fair value of stock options granted were as follows:

	December 31,
	2020		2019
Risk-free interest rate range		0.4%-1.2%		1.7%-2.5%
Dividend yield		0.0%		0.0%
Expected life of options (years)		5.5-6.5		5.8-6.0
Volatility rate range		88.8%-94.6%		83.7%-87.1%

The following table summarizes the Company’s stock option activity under the 2012 Plan:

	Number of shares			Weighted average exercise price		Weighted average remaining contractual term (in years)		Aggregate intrinsic value (in thousands)
Outstanding as of December 31, 2019		4,075,716		$	0.30		8.40	$	205
Granted		5,064,500			0.37		9.42
Exercised		(4,453,341	)		0.32		8.44		753
Forfeited or cancelled		(279,178	)		0.30		—
Outstanding as of December 31, 2020		4,407,697		$	0.36		9.03	$	574
Options vested and exercisable as of December 31, 2020		433,169		$	0.28		7.28	$	91

F-20

As of December 31, 2020, there was $1.5 million of unrecognized stock-based compensation expense related to the share-based compensation arrangements under the 2012 Plan. The Company expects to recognize this amount over a weighted-average period of 2.7 years.

The aggregate intrinsic value of options is calculated as the difference between the exercise price of the stock options and the fair value of the Company’s common stock for those stock options that had exercise prices lower than the fair value of the common stock as of the end of the reporting period. The weighted-average grant date fair value of the Company’s stock options granted during the years ended December 31, 2020 and December 31, 2019 was $0.28 and $0.25, respectively.

The total fair value of options vested during the years ended December 31, 2020 and 2019, was $0.1 million and $0.3 million, respectively.

Stock-based compensation expense

Stock-based compensation expense included in the Company’s consolidated statements of operations is as follows (in thousands):

	December 31,
	2020		2019
Research and development	$	174	$	79
General and administrative		293		169
Total stock-based compensation expense	$	467	$	248

10. Income taxes

Loss before provision for income taxes was as follows (in thousands):

	December 31,
	2020			2019
United States	$	(20,800	)	$	(15,003	)
	$	(20,800	)	$	(15,003	)

No deferred provisions for income taxes were recorded as of December 31, 2020 and 2019 respectively. The components of the current provision for income taxes are presented in the table below (in thousands):

	December 31,
	2020		2019
Current income tax provision (benefit):
State and local	$	2	$	2
Total provision (benefit) for income taxes	$	2	$	2

F-21

The following reconciles the differences between income taxes computed at the federal statutory rate and the provision for income taxes:

	December 31,
	2020			2019
Federal statutory income tax rate		21.0%			21.0%
State taxes		6.9%			6.7%
Valuation allowance		(31.5%	)		(31.1%	)
Re-measurement of deferred taxes due to Tax Cuts and Jobs Act		0.0%			0.0%
Gain on equity method investment		0.0%			0.0%
Other		3.6%			3.4%
Total		—%			—%

Deferred tax assets and liabilities reflect the net tax effects of net operating loss and tax credit carryforwards and temporary differences between the carrying amount of assets and liabilities for financial reporting and the amounts used for tax purposes. Significant components of the Company’s deferred tax assets and liabilities were as follows (in thousands):

	December 31,			December 31,
	2020			2019
Deferred tax assets:
Net operating loss carryforwards	$	13,496		$	7,684
Tax credits carryforward		1,708			756
Deferred rent		10			5
Accrued expenses		233			252
Stock-based compensation		22			20
Total deferred tax assets		15,469			8,718
Valuation allowance		(14,983	)		(8,426	)
Deferred tax assets	$	486		$	292
Deferred tax liabilities:
Depreciation	$	(213	)	$	(46	)
Prepaid expenses		(273	)		(246	)
Total deferred tax liabilities		(486	)		(292	)
Net deferred tax assets	$	—		$	—

F-22

The Company has evaluated the positive and negative evidence bearing upon its ability to realize the deferred tax assets. Management has considered the Company’s history of cumulative net losses incurred since inception and has concluded that it is more likely than not that the Company will not realize the benefits of the deferred tax assets. Accordingly, a full valuation allowance has been established against the net deferred tax assets as of December 31, 2020 and 2019. Management reevaluates the positive and negative evidence at each reporting period. Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2020 and 2019 related primarily to the increase in net operating loss carryforwards and Research and Development credits offset by the impact of the Tax Cuts and Jobs Act in 2017, and were as follows (in thousands):

	December 31,		December 31,
	2020		2019
Valuation allowance at beginning of year	$	8,426	$	3,757
Increases recorded to income tax provision		6,557		4,669
Valuation allowance at end of year	$	14,983	$	8,426

As of December 31, 2020, the Company has federal net operating loss carryforwards of $49.8 million. Net operating losses generated before 2018 of $4.6 million will expire at various dates through 2037, and net operating loss carryforwards of $45.2 million, which were generated after 2017, have an indefinite carryforward period. The Company has state net operating losses of approximately $48.3 million which begin to expire in 2034. The Company has Federal and State research and development tax credit carryforwards of $1.6 million and $0.5 million which will expire in 2034 and 2031, respectively.

Utilization of the Company’s net operating loss (“NOL”) carryforwards and research and development (“R&D”) credit carryforwards may be subject to a substantial annual limitation due to ownership change limitations that have occurred previously or that could occur in the future in accordance with Section 382 of the Internal Revenue Code of 1986 (“Section 382”) as well as similar state provisions. These ownership changes may limit the amount of NOL and R&D credit carryforwards that can be utilized annually to offset future taxable income and taxes, respectively. In general, an ownership change as defined by Section 382 results from transactions increasing the ownership of certain shareholders or public groups in the stock of a corporation by more than 50% over a three-year period. Since its formation the Company has raised capital through the issuance of capital stock on several occasions. These financings, combined with the purchasing shareholders’ subsequent disposition of those shares, could result in a change of control as defined by Section 382.

The Company recognizes both interest and penalties related to unrecognized tax benefits as a component of income tax expense. As of December 31, 2020, and 2019 respectively, there were no interest or penalties associated with unrecognized tax benefits. The following is a reconciliation of the total amount of unrecognized tax benefits (in thousands):

	December 31,
	2020		2019
Unrecognized benefit at beginning of year	$	906	$	906
Additions/reductions for tax positions related to the current year		1,191		—
Unrecognized benefit at end of year	$	2,097	$	906

The federal and state income tax returns are generally subject to examinations for the tax years ended December 31, 2017 through December 31, 2020. To the extent the Company has tax attribute carryforwards, the tax years in which the attribute was generated may still be adjusted upon examination by the Internal Revenue Service or state tax authorities to the extent utilized in a future period. The Company files income tax returns in the U.S. federal and various state jurisdictions. There are currently no federal or state audits in process.

F-23

11. Net loss per share

The Company’s potentially dilutive securities, which include preferred stock and stock options, have been excluded from the computation of diluted net loss per share as the effect would be to reduce the net loss per share. Therefore, the weighted-average number of common shares outstanding used to calculate both basic and diluted net loss per share attributable to common stockholders is the same. The Company excluded the following shares from the computation of diluted net loss per share attributable to common stockholders as of December 31, 2020 and 2019 because including them would have had an anti-dilutive effect:

	December 31,
	2020		2019
Series A Preferred Stock		5,817,996		5,817,996
Series B Preferred Stock		55,200,000		55,200,000
Options to purchase common stock		4,407,697		4,075,716
Unvested shares from early exercises		2,301,266		—

12. Commitments and contingencies

Lease commitments

On November 1, 2018, the Company entered into a lease agreement (the “lease”) for office space for a term of 5 years and the Company has the option to extend the term for one additional 3 year period. The Company received a tenant improvement allowance of $70 per square foot, which is being amortized as a reduction in rent expense over the lease term. The Company was also required to provide an initial security deposit in the form of a letter of credit, which is secured by cash on deposit of $0.1 million, which is recorded as restricted cash on the consolidated balance sheets. Rent expense, recognized on a straight-line basis over the term of the lease, for the years ended December 31, 2020 and December 31, 2019 was $0.5 million and $0.2 million, respectively.

On October 15, 2019, the Company entered into the First Amendment to the Lease (the “1st Amendment”) for additional office space at 128 Spring Street in Lexington, Massachusetts. The term of the 1st Amendment began on February 16, 2020 and runs co-terminus with the existing lease through October 31, 2023. The Company also has the same option to extend the term of the 1st Amendment for one additional 3 year period. The Company received a tenant improvement allowance of $60 per square foot. which is being amortized as a reduction in rent expense over the lease term. The Company was required to increase its total security deposit to $0.3 million as of the commencement date of the 1st Amendment.

The future minimum payments required under the lease as of December 31, 2020 are as follows (in thousands):

Year Ending December 31,
2021	$	715
2022		735
2023		627
	$	2,077

Legal proceedings

From time to time, in the ordinary course of business, the Company is subject to litigation and regulatory examinations as well as information gathering requests, inquiries and investigations. As of December 31, 2020, there were no matters which would have a material impact on the Company’s financial results.

F-24

13. Employee benefit plans

Effective January 1, 2019, the Company adopted a 401(k) retirement plan for its employees, which is designed to be qualified under Section 401(k) of the Internal Revenue Code. Eligible employees are permitted to contribute to the 401(k) plan within statutory and 401(k) plan limits. The Company has made no matching contributions during the years ended December 31, 2020 and 2019.

14. Subsequent events

The Company has evaluated events occurring after the date of its balance sheet through March 26, 2021, the date the financial statements were available to be issued, for potential recognition or disclosure in its financial statements.

In February 2021, the Company issued 21,784,885 shares of Series C redeemable convertible preferred stock in exchange for gross cash proceeds of $80.0 million. The rights and preferences of Series C are defined in the Amended and Restated Certificate of Incorporation and are consistent with the rights and preferences of the other series of preferred stock issued by the Company.

F-25

Cyteir Therapeutics, Inc.

                shares of common stock

J.P. Morgan	Morgan Stanley	BofA Securities
Wedbush PacGrow

                     , 2021

Through and including                    , 2021 (the 25th day after the date of this prospectus), all dealers effecting transactions in the Common Stock, whether or not participating in this offering, may be required to deliver a prospectus. This delivery requirement is in addition to a dealer’s obligation to deliver a prospectus when acting as an underwriter and with respect to an unsold allotment or subscription.

Part II

Information not required in prospectus

Item 13. Other expenses of issuance and distribution.

The following table sets forth the costs and expenses, other than the underwriting discounts and commissions, payable by the registrant in connection with the sale of common stock being registered. All amounts are estimates except for the SEC registration fee, the FINRA filing fee and the exchange listing fee:

Item	Amount to be paid
SEC registration fee	$	*
FINRA filing fee		*
Exchange listing fee		*
Printing and engraving expenses		*
Legal fees and expenses		*
Accounting fees and expenses		*
Transfer Agent fees and expenses		*
Miscellaneous expenses		*
Total	$	*

* To be completed by amendment

Item 14. Indemnification of directors and officers.

As permitted by Section 102(b)(7) of the DGCL, we plan to include in our amended and restated certificate of incorporation a provision to eliminate the personal liability of our directors for monetary damages for breach of their fiduciary duties as directors, subject to certain exceptions. In addition, our amended and restated certificate of incorporation and by-laws will provide that we are required to indemnify our officers and directors under certain circumstances, including those circumstances in which indemnification would otherwise be discretionary, and we are required to advance expenses to our officers and directors as incurred in connection with proceedings against them for which they may be indemnified, in each case except to the extent that the DGCL prohibits the elimination or limitation of liability of directors for breaches of fiduciary duty.

Section 145(a) of the DGCL provides that a corporation shall have the power to indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the right of the corporation) by reason of the fact that the person is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, against expenses (including attorneys’ fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by him in connection with such action, suit or proceeding if the person acted in good faith and in a manner the person reasonably believed to be in or not opposed to the best interest of the corporation, and, with respect to any criminal action or proceeding, had no reasonable cause to believe his conduct was unlawful. The termination of any action, suit or proceeding by judgment, order, settlement, conviction or upon a plea of nolo contendere or its equivalent shall not, of itself, create a presumption that the person did not act in good faith and in a manner which the person reasonably believed to be in or not opposed to the best interests of the corporation, and, with respect to any criminal action or proceeding, had reasonable cause to believe that his conduct was unlawful.

II-1

Section 145(b) of the DGCL provides that a corporation shall have the power to indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action or suit by or in the right of the corporation to procure a judgment in its favor by reason of the fact that the person is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise against expenses (including attorneys’ fees) actually and reasonably incurred by him in connection with the defense or settlement of such action or suit if the person acted in good faith and in a manner the person reasonably believed to be in or not opposed to the best interests of the corporation and except that no indemnification shall be made with respect to any claim, issue or matter as to which such person shall have been adjudged to be liable to the corporation unless and only to the extent that the Court of Chancery or the court in which such action or suit was brought shall determine upon application that, despite the adjudication of liability but in view of all the circumstances of the case, such person is fairly and reasonably entitled to indemnity for such expenses which the Court of Chancery or such other court shall deem proper.

We expect to enter into indemnification agreements with our directors and officers prior to the completion of this offering. These indemnification agreements will provide broader indemnity rights than those provided under the DGCL and our amended and restated certificate of incorporation. These indemnification agreements are not intended to deny or otherwise limit third-party or derivative suits against us or our directors or officers, but to the extent a director or officer were entitled to indemnity or contribution under the indemnification agreement, the financial burden of a third-party suit would be borne by us, and we would not benefit from derivative recoveries against the director or officer. Such recoveries would accrue to our benefit but would be offset by our obligations to the director or officer under the indemnification agreement.

The underwriting agreement will provide that the underwriters are obligated, under certain circumstances, to indemnify our directors, officers and controlling persons against certain liabilities, including liabilities under the Securities Act.

We maintain directors’ and officers’ liability insurance for the benefit of our directors and officers.

Item 15. Recent sales of unregistered securities.

In the three years preceding the filing of this registration statement, we have issued the following securities that were not registered under the Securities Act:

Issuances of capital stock

In 2018, we issued an aggregate of 17,499,993 shares of our Series B convertible preferred stock for aggregate consideration of $17,499,993 to 12 accredited investors.

In 2019, we issued an aggregate of 37,700,007 shares of our Series B convertible preferred stock for aggregate consideration of $37,700,007 to 14 accredited investors.

In 2021, we issued an aggregate of 21,784,885 shares of our Series C convertible preferred stock for aggregate consideration of $79,999,980 to 22 accredited investors.

All sales of securities described above were made in reliance upon the exemption from registration provided by Section 4(a)(2) of the Securities Act for transactions by an issuer not involving a public offering. No underwriters were involved in the sales and the certificates representing the securities sold and issued contain legends restricting transfer of the securities without registration under the Securities Act or an applicable exemption from registration.

II-2

Grants of stock options and restricted stock

Since March 19, 2018, we have granted stock options to purchase an aggregate of 13,417,922 shares of our common stock at a weighted-average exercise price of $0.87 to employees, directors and consultants.

The issuance of the above securities were exempt either pursuant to Rule 701, as transactions pursuant to a compensatory benefit plan, or pursuant to Section 4(a)(2), as transactions by an issuer not involving a public offering.

Item 16. Exhibits and consolidated financial statement schedules.

(a) Exhibits

Exhibit number	Description of document
1.1*	Form of Underwriting Agreement
3.1	Fifth Amended and Restated Certificate of Incorporation of Cyteir Therapeutics, Inc.
3.2*	Certificate of Amendment to Fifth Amended and Restated Certificate of Incorporation of Cyteir Therapeutics, Inc.
3.3*	Form of Sixth Amended and Restated Certificate of Incorporation of Cyteir Therapeutics, Inc. (to be effective upon the closing of this offering)
3.4	Amended and Restated By-laws of Cyteir Therapeutics, Inc.
3.5*	Form of Second Amended and Restated By-laws of Cyteir Therapeutics, Inc. (to be effective upon the closing of this offering)
4.1*	Specimen stock certificate evidencing shares of common stock
4.2	Second Amended and Restated Investors’ Rights Agreement, by and among Cyteir Therapeutics, Inc. and the investors party thereto, dated as of February 5, 2021
5.1*	Opinion of Ropes & Gray LLP
10.1	Lease Agreement by and between 128 Spring Street Lexington, LLC and Cyteir Therapeutics, Inc., dated August 8, 2018
10.2	First Amendment to Lease Agreement by and between 128 Spring Street Lexington, LLC and Cyteir Therapeutics, Inc., dated October 15, 2019
10.3*	Cyteir Therapeutics, Inc. 2012 Stock Incentive Plan, as amended
10.4*	Form of Stock Restriction Agreement under the Cyteir Therapeutics, Inc. 2012 Stock Incentive Plan
10.5*	Form of Incentive Stock Option Grant Notice under the Cyteir Therapeutics, Inc. 2012 Stock Incentive Plan
10.6*	Form of Non-Qualified Stock Option Grant Notice under the Cyteir Therapeutics, Inc. 2012 Stock Incentive Plan
10.7*	Form of Indemnification Agreement between Cyteir Therapeutics, Inc. and its directors and officers
10.8*	Amended and Restated Letter Agreement between Cyteir Therapeutics, Inc. and Markus Renschler, M.D., dated                     , 2021
10.9*	Amended and Restated Letter Agreement between Cyteir Therapeutics, Inc. and Andrew Gengos, dated                     , 2021
10.10*	Amended and Restated Letter Agreement between Cyteir Therapeutics, Inc. and Paul Secrist, Ph.D., dated                     , 2021

II-3

Exhibit number	Description of document
10.11*	Cyteir Therapeutics, Inc. 2021 Stock Incentive Plan
10.12*	Form of Restricted Stock Agreement under the Cyteir Therapeutics, Inc. 2021 Stock Incentive Plan
10.13*	Form of Incentive Stock Option Grant Notice under the Cyteir Therapeutics, Inc. 2021 Stock Incentive Plan
10.14*	Form of Non-Qualified Stock Option Grant Notice under the Cyteir Therapeutics, Inc. 2021 Stock Incentive Plan
21.1	List of Subsidiaries of Cyteir Therapeutics, Inc.
23.1*	Consent of Ernst & Young LLP
23.2*	Consent of Ropes & Gray LLP (included in Exhibit 5.1)
24.1*	Power of Attorney (included on signature page)

* To be filed by amendment

(b) Consolidated Financial Statement Schedules

Schedules not listed above have been omitted because the information required to be set forth therein is not applicable or is shown in the consolidated financial statements or notes thereto.

Item 17. Undertakings.

The undersigned Registrant hereby undertakes to provide to the underwriters at the closing specified in the underwriting agreement certificates in such denominations and registered in such names as required by the underwriters to permit prompt delivery to each purchaser.

Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers and controlling persons of the Registrant pursuant to the foregoing provisions, or otherwise, the Registrant has been advised that in the opinion of the SEC such indemnification is against public policy as expressed in the Securities Act, and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or paid by a director, officer, or controlling person of the Registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the Registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question of whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

The undersigned Registrant hereby undertakes that:

1. For purposes of determining any liability under the Securities Act, the information omitted from the form of prospectus filed as part of this Registration Statement in reliance upon Rule 430A and contained in a form of prospectus filed by the Registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act shall be deemed to be part of this Registration Statement as of the time it was declared effective.

2. For the purpose of determining any liability under the Securities Act, each post-effective amendment that contains a form of prospectus shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

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Signatures

Pursuant to the requirements of the Securities Act of 1933, the registrant has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Lexington, Commonwealth of Massachusetts, on                    , 2021.

CYTEIR THERAPEUTICS, INC.
By:
	Markus Renschler, M.D. President and Chief Executive Officer

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Markus Renschler, M.D. and David Gaiero, and each of them singly, our true and lawful attorneys, with full power to them, and to each of them singly, to sign for us and in our names in the capacities indicated below, the registration statement on Form S-1 filed herewith, and any and all pre-effective and post-effective amendments to said registration statement, and any registration statement filed pursuant to Rule 462(b) under the Securities Act of 1933, as amended, in connection with the registration under the Securities Act of 1933, as amended, of equity securities of the Company, and to file or cause to be filed the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as each of us might or could do in person, and hereby ratifying and confirming all that said attorneys, and each of them, or their substitute or substitutes, shall do or cause to be done by virtue of this Power of Attorney.

Pursuant to the requirements of the Securities Act of 1933, as amended, this registration statement has been signed by the following persons in the capacities and on the dates indicated:

Signature	Title	Date
Markus Renschler, M.D.	President, Chief Executive Officer and Director (Principal Executive Officer)	, 2021
David Gaiero	David Gaiero (Principal Accounting and Financial Officer)	, 2021
Racquel Bracken	Director	, 2021
Jean George, M.B.A.	Director	, 2021
Karen Hong, Ph.D.	Director	, 2021
Susan Molineaux, Ph.D.	Director	, 2021
Janwillem Naesens, M.Sc., M.B.A.	Director	, 2021
Timothy Romberger	Director	, 2021
Joseph S. Zakrzewski	Director	, 2021

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EX-3.1

Exhibit 3.1

FIFTH AMENDED AND RESTATED

CERTIFICATE OF INCORPORATION

OF

CYTEIR THERAPEUTICS, INC.

(Pursuant to Sections 242 and 245 of the

General Corporation Law of the State of Delaware)

Cyteir Therapeutics, Inc., a corporation organized and existing under and by virtue of the provisions of the General Corporation Law of the State of Delaware (the “General Corporation Law”),

DOES HEREBY CERTIFY:

1. That the name of this corporation is Cyteir Therapeutics, Inc., and that this corporation was originally incorporated pursuant to the General Corporation Law on June 4, 2012.

2. That the Board of Directors duly adopted resolutions proposing to amend and restate the Fourth Amended and Restated Certificate of Incorporation of this corporation, declaring said amendment and restatement to be advisable and in the best interests of this corporation and its stockholders, and authorizing the appropriate officers of this corporation to solicit the consent of the stockholders therefor, which resolution setting forth the proposed amendment and restatement is as follows:

RESOLVED, that the Fourth Amended and Restated Certificate of Incorporation of this corporation be amended and restated in its entirety to read as follows:

FIRST: The name of this corporation is Cyteir Therapeutics, Inc., (the “Corporation”).

SECOND: The address of the registered office of the Corporation in the State of Delaware is 1209 Orange Street, in the City of Wilmington, County of New Castle, 19801. The name of its registered agent at such address is The Corporation Trust Company.

THIRD: The nature of the business or purposes to be conducted or promoted is to engage in any lawful act or activity for which corporations may be organized under the General Corporation Law.

FOURTH: The total number of shares of all classes of stock which the Corporation shall have authority to issue is (i) 114,000,000 shares of Common Stock, $0.001 par value per share (“Common Stock”), and (ii) 82,802,881 shares of Preferred Stock, $0.001 par value per share (“Preferred Stock”).

The following is a statement of the designations and the powers, privileges and rights, and the qualifications, limitations or restrictions thereof in respect of each class of capital stock of the Corporation.

A. COMMON STOCK

1. General. The voting, dividend and liquidation rights of the holders of the Common Stock are subject to and qualified by the rights, powers and preferences of the holders of the Preferred Stock set forth herein.

2. Voting. The holders of the Common Stock are entitled to one (1) vote for each share of Common Stock held at all meetings of stockholders (and written actions in lieu of meetings); provided, however, that, except as otherwise required by law, holders of Common Stock, as such, shall not be entitled to vote on any amendment to the Certificate of Incorporation that relates solely to the terms of one (1) or more outstanding series of Preferred Stock if the holders of such affected series are entitled, either separately or together with the holders of one (1) or more other such series, to vote thereon pursuant to the Certificate of Incorporation or pursuant to the General Corporation Law. There shall be no cumulative voting. The number of authorized shares of Common Stock may be increased or decreased (but not below the number of shares thereof then outstanding) by (in addition to any vote of the holders of one (1) or more series of Preferred Stock that may be required by the terms of the Certificate of Incorporation) the affirmative vote of the holders of shares of capital stock of the Corporation representing a majority of the votes represented by all outstanding shares of capital stock of the Corporation entitled to vote, irrespective of the provisions of Section 242(b)(2) of the General Corporation Law.

B. PREFERRED STOCK

5,817,996 shares of the authorized Preferred Stock of the Corporation are hereby designated “Series A Preferred Stock” with the following rights, preferences, powers, privileges and restrictions, qualifications and limitations. 55,200,000 shares of the authorized Preferred Stock of the Corporation are hereby designated “Series B Preferred Stock” with the following rights, preferences, powers, privileges and restrictions, qualifications and limitations. 21,784,885 shares of the authorized and unissued Preferred Stock of the Corporation are hereby designated “Series C Preferred Stock” with the following rights, preferences, powers, privileges and restrictions, qualifications and limitations. Unless otherwise indicated, references to “sections” or “subsections” in this Part B of this Article Fourth refer to sections and subsections of Part B of this Article Fourth.

1. Dividends. From and after the date of the issuance of any shares of Preferred Stock, dividends at the rate per annum of eight percent (8%) of the applicable Original Issue Price (as defined below) of such series of Preferred Stock shall accrue on such shares of Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to the Preferred Stock) (the “Accruing Dividends”). Accruing Dividends shall accrue from day to day, whether or not declared, and shall not be cumulative nor compounded; provided however, that except as set forth in the following sentence of this Section 1 or in Subsection 2.1, such Accruing Dividends shall be payable only when, as, and if declared by the Board of Directors and the Corporation shall be under no obligation to pay such Accruing Dividends. The Corporation shall not declare, pay or set aside any dividends on shares of any other class or series of capital stock of the Corporation (other than dividends on shares of Common Stock payable in shares of Common Stock) unless (in addition to the obtaining of any consents required elsewhere in the Certificate of Incorporation) the holders of

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the Preferred Stock then outstanding shall first receive, or simultaneously receive, a dividend on each outstanding share of Preferred Stock in an amount at least equal to the sum of (i) the amount of the aggregate Accruing Dividends then accrued on such share of Preferred Stock and not previously paid and (ii) (A) in the case of a dividend on Common Stock or any class or series that is convertible into Common Stock, that dividend per share of Preferred Stock as would equal the product of (1) the dividend payable on each share of such class or series determined, if applicable, as if all shares of such class or series had been converted into Common Stock and (2) the number of shares of Common Stock issuable upon conversion of a share of Preferred Stock, in each case calculated on the record date for determination of holders entitled to receive such dividend or (B) in the case of a dividend on any class or series that is not convertible into Common Stock, at a rate per share of Preferred Stock determined by (1) dividing the amount of the dividend payable on each share of such class or series of capital stock by the original issuance price of such class or series of capital stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to such class or series) and (2) multiplying such fraction by an amount equal to the applicable Original Issue Price; provided that, if the Corporation declares, pays or sets aside, on the same date, a dividend on shares of more than one (1) class or series of capital stock of the Corporation, the dividend payable to the holders of Preferred Stock pursuant to this Section 1 shall be calculated based upon the dividend on the class or series of capital stock that would result in the highest Preferred Stock dividend. The “Original Issue Price” shall mean (i) $1.00 per share for the Series A Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to the Series A Preferred Stock); (ii) $1.00 per share for the Series B Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to the Series B Preferred Stock) and (iii) $3.67227 per share for the Series C Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to the Series C Preferred Stock).

In the event that the Board of Directors of the Corporation determines, subject to Section 3.3 below, and without limiting Section 2 below, to distribute (x) the proceeds (cash or otherwise) resulting from any sale, lease, license or other transfer of a significant portion of its assets or (y) the proceeds from any option to acquire securities or assets of the Corporation, the proceeds resulting therefrom (including in respect of any ongoing payments, such as milestone payments) shall be distributed in accordance with Section 2 below (and the amounts subsequently distributable pursuant to Section 2 will be reduced, or adjusted, as applicable, to take into account all payments made pursuant to this paragraph as if such payments, along with the consideration then payable under Section 2, had been paid in a single transaction), and not this Section 1.

2. Liquidation, Dissolution or Winding Up; Certain Mergers, Consolidations and Asset Sales.

2.1 Preferential Payments to Holders of Preferred Stock. In the event of any voluntary or involuntary liquidation, dissolution or winding up of the Corporation or Deemed Liquidation Event (as defined below), the holders of shares of Preferred Stock then outstanding shall be entitled to be paid out of the assets of the Corporation, the consideration payable to the stockholders or the Available Proceeds available for distribution to its stockholders before any payment shall be made to the holders of Common Stock by reason of their ownership thereof, an

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amount per share equal to the greater of (i) the Original Issue Price, plus any Accruing Dividends accrued but unpaid thereon, together with any other dividends declared but unpaid thereon, or (ii) such amount per share as would have been payable had all shares of the applicable series of Preferred Stock been converted into Common Stock pursuant to Section 4 immediately prior to such liquidation, dissolution, winding up or Deemed Liquidation Event (the amount payable pursuant to this sentence is hereafter referred to as the “Liquidation Amount”). If upon any such liquidation, dissolution or winding up of the Corporation or Deemed Liquidation Event, the assets of the Corporation, the consideration payable to the stockholders or the Available Proceeds available for distribution to its stockholders shall be insufficient to pay the holders of shares of Preferred Stock the full amount to which they shall be entitled under this Subsection 2.1, the holders of shares of Preferred Stock shall share ratably in any distribution of the assets available for distribution in proportion to the respective amounts which would otherwise be payable in respect of the shares held by them upon such distribution if all amounts payable on or with respect to such shares were paid in full.

2.2 Distribution of Remaining Assets. In the event of any voluntary or involuntary liquidation, dissolution or winding up of the Corporation or Deemed Liquidation Event, after the payment of all preferential amounts required to be paid to the holders of shares of Preferred Stock the remaining assets of the Corporation, the consideration payable to the stockholders or the Available Proceeds available for distribution to its stockholders shall be distributed among the holders of the shares of Common Stock, pro rata based on the number of shares held by each such holder.

2.3 Deemed Liquidation Events.

2.3.1 Definition. Each of the following events shall be considered a “Deemed Liquidation Event” unless (i) the holders of at least a majority of the then outstanding shares of Preferred Stock (voting as a single class on an as-converted basis) (the “Requisite Holders”) and (ii) the holders of at least a majority of the then outstanding shares of Series C Preferred Stock, which majority must include at least one holder of shares of Series C Preferred Stock that does not also, and whose Affiliates do not, hold shares of Series B Preferred Stock or Series A Preferred Stock (the “Series C Majority”), elect otherwise by written notice sent to the Corporation at least five (5) days prior to the effective date of any such event:

(a) a merger or consolidation in which

(i) the Corporation is a constituent party or

(ii) a subsidiary of the Corporation is a constituent party and the Corporation issues shares of its capital stock pursuant to such merger or consolidation,

except any such merger or consolidation involving the Corporation or a subsidiary in which the shares of capital stock of the Corporation outstanding immediately prior to such merger or consolidation continue to represent, or are converted into or exchanged for shares of capital stock that represent, immediately following such merger or consolidation, at least a majority, by voting power, of the capital stock of (1) the surviving or resulting corporation or (2) if the surviving or resulting corporation is a wholly owned subsidiary of another corporation immediately following such merger or consolidation, the parent corporation of such surviving or resulting corporation; or

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(b) the sale, lease, transfer, exclusive license or other disposition, in a single transaction or series of related transactions, by the Corporation or any subsidiary of the Corporation of all or substantially all the assets, or substantially all of the intellectual property (without a material field or geography limitation), of the Corporation and its subsidiaries taken as a whole, or the sale or disposition (whether by merger, consolidation or otherwise, and whether in a single transaction or a series of related transactions) of one (1) or more subsidiaries of the Corporation if substantially all of the assets or intellectual property of the Corporation and its subsidiaries taken as a whole are held by such subsidiary or subsidiaries, except where such sale, lease, transfer, exclusive license or other disposition is to a wholly owned subsidiary of the Corporation.

2.3.2 Effecting a Deemed Liquidation Event.

(a) The Corporation shall not have the power to effect a Deemed Liquidation Event referred to in Subsection 2.3.1(a)(i) unless the agreement or plan of merger or consolidation for such transaction (the “Merger Agreement”) provides that the consideration payable to the stockholders of the Corporation shall be allocated among the holders of capital stock of the Corporation in accordance with Subsections 2.1 and 2.2.

(b) In the event of a Deemed Liquidation Event referred to in Subsection 2.3.1(a)(ii) or 2.3.1(b), if the Corporation does not effect a dissolution of the Corporation under the General Corporation Law within ninety (90) days after such Deemed Liquidation Event, then (i) the Corporation shall send a written notice to each holder of Preferred Stock no later than the ninetieth (90^th) day after the Deemed Liquidation Event advising such holders of their right (and the requirements to be met to secure such right) pursuant to the terms of the following clause (ii) to require the redemption of such shares of Preferred Stock, and (ii) if the Requisite Holders so request in a written instrument delivered to the Corporation not later than one hundred and twenty (120) days after such Deemed Liquidation Event, the Corporation shall use the consideration received by the Corporation for such Deemed Liquidation Event (net of any retained liabilities associated with the assets sold or technology licensed, as determined in good faith by the Board of Directors of the Corporation), together with any other assets of the Corporation available for distribution to its stockholders, all to the extent permitted by Delaware law governing distributions to stockholders (the “Available Proceeds”), on the one hundred and fiftieth (150^th) day after such Deemed Liquidation Event (the “Redemption Date”), to redeem all outstanding shares of Preferred Stock at a price per share equal to the applicable Liquidation Amount (the “Redemption Price”). Notwithstanding the foregoing, in the event of a redemption pursuant to the preceding sentence, if the Available Proceeds are not sufficient to redeem all outstanding shares of Preferred Stock, the Corporation shall ratably redeem each holder’s shares of Preferred Stock to the fullest extent of such Available Proceeds, and shall redeem the remaining shares as soon as it may lawfully do so under Delaware law governing distributions to stockholders. The Corporation shall send written notice of the mandatory redemption (the “Redemption Notice”) to each holder of record of Preferred Stock not less than forty-five (45) days prior to the Redemption Date. The Redemption Notice shall state: (i) the number of shares

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of Preferred Stock held by the holder that the Corporation shall redeem on the Redemption Date specified in the Redemption Notice; (ii) the Redemption Date and the Redemption Price; (iii) the date upon which the holder’s right to convert such shares terminates (as determined in accordance with Subsection 4.1); and (iv) for holders of shares in certificated form, that the holder is to surrender to the Corporation, in the manner and at the place designated, his, her or its certificate or certificates representing the shares of Preferred Stock to be redeemed. Each holder of shares of Preferred Stock to be redeemed, shall surrender the certificate or certificates representing such shares (or, if such registered holder alleges that such certificate has been lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably acceptable to the Corporation to indemnify the Corporation against any claim that may be made against the Corporation on account of the alleged loss, theft or destruction of such certificate) to the Corporation, and thereupon the consideration for such shares shall be payable to the order of the person whose name appears on such certificate or certificates as the owner thereof. If the consideration payable upon redemption of the shares of Preferred Stock to be redeemed pursuant to this Subsection 2.3.2(b) is paid or tendered for payment or deposited with an independent payment agent so as to be available therefor in a timely manner, then notwithstanding that the certificates evidencing any of the shares of Preferred Stock so redeemed shall not have been surrendered, dividends with respect to such shares of Preferred Stock shall cease to accrue and all rights with respect to such shares shall forthwith terminate. Prior to the distribution or redemption provided for in this Subsection 2.3.2(b), the Corporation shall not expend or dissipate the consideration received for such Deemed Liquidation Event, except to discharge expenses incurred in connection with such Deemed Liquidation Event or in the ordinary course of business.

2.3.3 Amount Deemed Paid or Distributed. The amount deemed paid or distributed to the holders of capital stock of the Corporation upon any such merger, consolidation, sale, transfer, exclusive license, other disposition or redemption shall be the cash or the value of the property, rights or securities paid or distributed to such holders by the Corporation or the acquiring person, firm or other entity. The value of such property, rights or securities shall be determined in good faith by the Board of Directors of the Corporation, which must include a majority of the Preferred Directors (as defined below), provided that if the number of Preferred Directors then in office is two (2) or less, then only the vote of one (1) of the Preferred Directors shall be required (the “Requisite Directors”).

2.3.4 Allocation of Escrow and Contingent Consideration. In the event of a Deemed Liquidation Event, if any portion of the consideration payable to the stockholders of the Corporation is payable only upon satisfaction of contingencies (the “Additional Consideration”), the definitive documentation effecting the Deemed Liquidation Event shall provide that (a) the portion of such consideration that is not Additional Consideration (such portion, the “Initial Consideration”) shall be allocated among the holders of capital stock of the Corporation in accordance with Subsections 2.1 and 2.2 as if the Initial Consideration were the only consideration payable in connection with such Deemed Liquidation Event and (b) any Additional Consideration which becomes payable to the stockholders of the Corporation upon satisfaction of such contingencies shall be allocated among the holders of capital stock of the Corporation in accordance with Subsections 2.1 and 2.2 after taking into account the previous payment of the Initial Consideration as part of the same transaction. For the purposes of this Subsection 2.3.4, consideration placed into escrow or retained as holdback to be available for satisfaction of indemnification or similar obligations in connection with such Deemed Liquidation Event shall be deemed to be Additional Consideration.

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3. Voting.

3.1 General. On any matter presented to the stockholders of the Corporation for their action or consideration at any meeting of stockholders of the Corporation (or by written consent of stockholders in lieu of meeting), each holder of outstanding shares of Preferred Stock shall be entitled to cast the number of votes equal to the number of whole shares of Common Stock into which the shares of Preferred Stock held by such holder are convertible as of the record date for determining stockholders entitled to vote on such matter. Except as provided by law or by the other provisions of the Certificate of Incorporation, holders of Preferred Stock shall vote together with the holders of Common Stock as a single class.

3.2 Election of Directors. At any time there when at least 8,000,000 shares of Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to the Preferred Stock) are outstanding, the holders of shares of Preferred Stock, voting together as a single class, shall be entitled to elect at least four (4) directors of the Corporation (together, the “Preferred Directors”). Any director elected as provided in the preceding sentence may be removed without cause by, and only by, the affirmative vote of the holders of Preferred Stock, given either at a special meeting of such stockholders duly called for that purpose or pursuant to a written consent of stockholders. If the holders of shares of Preferred Stock fail to elect a sufficient number of directors to fill all directorships for which they are entitled to elect directors, voting exclusively and as a separate class, pursuant to the first sentence of this Subsection 3.2, then any directorship not so filled shall remain vacant until such time as the holders of the Preferred Stock elect a person to fill such directorship by vote or written consent in lieu of a meeting; and no such directorship may be filled by stockholders of the Corporation other than by the holders of Preferred Stock, voting exclusively and as a separate class. The holders of shares of Common Stock shall be entitled to elect one (1) director of the Corporation (the “Common Director”). The director elected as provided in the preceding sentence may be removed without cause by, and only by, the affirmative vote of the holders of Common Stock, given either at a special meeting of such stockholders duly called for that purpose or pursuant to a written consent of stockholders. If the holders of shares of Common Stock fail to elect a director to fill the directorship for which they are entitled to elect a director, voting exclusively and as a separate class, pursuant to the first sentence of this Subsection 3.2, then such directorship not so filled shall remain vacant until such time as the holders of the Common Stock elect a person to fill such directorship by vote or written consent in lieu of a meeting; and no such directorship may be filled by stockholders of the Corporation other than by the holders of Common Stock, voting exclusively and as a separate class. The holders of record of the shares of Common Stock and Preferred Stock, voting together as a single class, shall be entitled to elect the balance of the total number of directors of the Corporation. At any meeting held for the purpose of electing a director, the presence in person or by proxy of the holders of a majority of the outstanding shares of the class or series entitled to elect such director shall constitute a quorum for the purpose of electing such director. Except as otherwise provided in this Subsection 3.2, a vacancy in any directorship filled by the holders of any class or series shall be filled only by vote or written consent in lieu of a meeting of the holders of such class or series or by any remaining director or directors elected by the holders of such class or series pursuant to this Subsection 3.2. Notwithstanding the foregoing, the directors elected in the same action whereby the Corporation’s board of directors approved this Certificate of Incorporation can fill the directorships designated by the board of directors in such action including serving as a Preferred Director or the Common Director, as may be indicated in such action.

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3.3 Preferred Stock Protective Provisions. At any time when at least 8,000,000 shares of Preferred Stock (subject to appropriate adjustment in the event of any stock dividend, stock split, combination or other similar recapitalization with respect to any series of the Preferred Stock) are outstanding, the Corporation shall not, either directly or indirectly by amendment, merger, consolidation or otherwise, do any of the following without (in addition to any other vote required by law or the Certificate of Incorporation) the written consent or affirmative vote of the Requisite Holders, and, in the case of Subsection 3.3.3 only, the written consent or affirmative vote of the Series C Majority, and any such act or transaction entered into without such consent or vote shall be null and void ab initio, and of no force or effect:

3.3.1 take any action that would result in altering or changing the rights, preferences or privileges of any series of Preferred Stock;

3.3.2 increase or decrease (other than for decreases resulting from conversion of the Preferred Stock) the authorized number of shares of the Common Stock, Series A Preferred Stock, or Series B Preferred Stock;

3.3.3 increase or decrease (other than for decreases resulting from conversion of the Series C Preferred Stock) the authorized number of shares of the Series C Preferred Stock;

3.3.4 authorize, create or issue (by reclassification, merger or otherwise), or obligate itself to issue, any new class or series of equity security (including any security convertible into or exercisable for any equity security) having rights, preferences or privileges senior to or on a parity with any series of Preferred Stock;

3.3.5 purchase or redeem (or permit any subsidiary to purchase or redeem) or pay or declare any dividend or make any distribution on, any shares of capital stock of the Corporation prior to the Preferred Stock as expressly authorized herein, other than repurchases of stock from former employees, officers, directors, consultants or other persons who performed services for the Corporation or any subsidiary in connection with the cessation of such employment or service at the lower of the original purchase price or the then- current fair market value thereof;

3.3.6 liquidate, dissolve or wind-up the business and affairs of the Corporation, effect any merger, reorganization or consolidation, any other transaction that results in the sale of all or substantially all the outstanding capital stock or assets of the Corporation, or any other Deemed Liquidation Event, or consent to any of the foregoing;

3.3.7 amend, alter or repeal any provision of the Certificate of Incorporation or Bylaws of the Corporation;

3.3.8 change the number of directors constituting the Board of Directors from eight (8);

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3.3.9 take any action that would result in the payment or declaration of any dividend on any shares of Common Stock or Preferred Stock;

3.3.10 create, or hold capital stock in, any subsidiary that is not wholly owned (either directly or through one (1) or more other subsidiaries) by the Corporation, or sell, transfer or otherwise dispose of any capital stock of any direct or indirect subsidiary of the Corporation, or permit any direct or indirect subsidiary to sell, lease, transfer, exclusively license or otherwise dispose (in a single transaction or series of related transactions) of all or substantially all of the assets of such subsidiary;

3.3.11 acquire, or permit any direct or indirect subsidiary to acquire (in a single transaction or series of related transactions) all or substantially all of the assets of another entity, unless such action has received the prior approval of the Board of Directors, including the Requisite Directors (so long as all directors have received prior notice of such action);

3.3.12 increase the number of shares of Common Stock available for grant or issuance under the Corporation’s equity incentive plan, or authorize or establish a new plan or arrangement providing for the grant or issuance of shares of Common Stock, options, or convertible securities to directors, employees, or consultants of the Corporation; or

3.3.13 enter into any agreement to do any of the foregoing.

4. Optional Conversion.

The holders of Preferred Stock shall have conversion rights as follows (the “Conversion Rights”):

4.1 Right to Convert.

4.1.1 Conversion Ratio. Subject to Section 5A, each share of Preferred Stock shall be convertible, at the option of the holder thereof, at any time and from time to time, and without the payment of additional consideration by the holder thereof, into such number of fully paid and nonassessable shares of Common Stock as is determined by dividing the Original Issue Price for such series of Preferred Stock by the Conversion Price (as defined below) for such series of Preferred Stock in effect at the time of conversion (the “Conversion Ratio”). The “Conversion Price” shall initially be equal to $1.00 for the Series A Preferred Stock, $1.00 for the Series B Preferred Stock and $3.67227 for the Series C Preferred Stock. Such initial Conversion Price, and the rate at which shares of Preferred Stock may be converted into shares of Common Stock, shall be subject to adjustment as provided below.

4.1.2 Termination of Conversion Rights. In the event of a notice of redemption of any shares of Preferred Stock pursuant to Section 6, the Conversion Rights of the shares designated for redemption shall terminate at the close of business on the last full day preceding the date fixed for redemption, unless the redemption price is not fully paid on such redemption date, in which case the Conversion Rights for such shares shall continue until such price is paid in full. In the event of a liquidation, dissolution or winding up of the Corporation or a Deemed Liquidation Event, the Conversion Rights shall terminate at the close of business on the last full day preceding the date fixed for the payment of any such amounts distributable on such event to the holders of Preferred Stock.

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4.2 Fractional Shares. No fractional shares of Common Stock shall be issued upon conversion of the Preferred Stock. In lieu of any fractional shares to which the holder would otherwise be entitled, the Corporation shall pay cash equal to such fraction multiplied by the fair market value of a share of Common Stock as determined in good faith by the Board of Directors of the Corporation. Whether or not fractional shares would be issuable upon such conversion shall be determined on the basis of the total number of shares of Preferred Stock the holder is at the time converting into Common Stock and the aggregate number of shares of Common Stock issuable upon such conversion.

4.3 Mechanics of Conversion.

4.3.1 Notice of Conversion. In order for a holder of Preferred Stock to voluntarily convert shares of Preferred Stock into shares of Common Stock, such holder shall surrender the certificate or certificates for such shares of Preferred Stock (or, if such registered holder alleges that such certificate has been lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably acceptable to the Corporation to indemnify the Corporation against any claim that may be made against the Corporation on account of the alleged loss, theft or destruction of such certificate), at the office of the transfer agent for the Preferred Stock (or at the principal office of the Corporation if the Corporation serves as its own transfer agent), together with written notice that such holder elects to convert all or any number of the shares of the Preferred Stock represented by such certificate or certificates and, if applicable, any event on which such conversion is contingent. Such notice shall state such holder’s name or the names of the nominees in which such holder wishes the certificate or certificates for shares of Common Stock to be issued. If required by the Corporation, certificates surrendered for conversion shall be endorsed or accompanied by a written instrument or instruments of transfer, in form satisfactory to the Corporation, duly executed by the registered holder or his, her or its attorney duly authorized in writing. The close of business on the date of receipt by the transfer agent (or by the Corporation if the Corporation serves as its own transfer agent) of such certificates (or lost certificate affidavit and agreement) and notice shall be the time of conversion (the “Conversion Time”), and the shares of Common Stock issuable upon conversion of the shares represented by such certificate shall be deemed to be outstanding of record as of such date. The Corporation shall, as soon as practicable after the Conversion Time, (i) issue and deliver to such holder of Preferred Stock, or to his, her or its nominees, a certificate or certificates for the number of full shares of Common Stock issuable upon such conversion in accordance with the provisions hereof and a certificate for the number (if any) of the shares of Preferred Stock represented by the surrendered certificate that were not converted into Common Stock, (ii) pay in cash such amount as provided in Subsection 4.2 in lieu of any fraction of a share of Common Stock otherwise issuable upon such conversion and (iii) pay all declared but unpaid dividends on the shares of Preferred Stock converted.

4.3.2 Reservation of Shares. The Corporation shall at all times when the Preferred Stock shall be outstanding, reserve and keep available out of its authorized but unissued capital stock, for the purpose of effecting the conversion of the Preferred Stock, such number of its duly authorized shares of Common Stock as shall from time to time be sufficient to effect the conversion of all outstanding Preferred Stock; and if at any time the number of authorized

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but unissued shares of Common Stock shall not be sufficient to effect the conversion of all then outstanding shares of the Preferred Stock, the Corporation shall take such corporate action as may be necessary to increase its authorized but unissued shares of Common Stock to such number of shares as shall be sufficient for such purposes, including, without limitation, engaging in best efforts to obtain the requisite stockholder approval of any necessary amendment to the Certificate of Incorporation. Before taking any action which would cause an adjustment reducing the Conversion Price below the then par value of the shares of Common Stock issuable upon conversion of the Preferred Stock, the Corporation will take any corporate action which may, in the opinion of its counsel, be necessary in order that the Corporation may validly and legally issue fully paid and nonassessable shares of Common Stock at such adjusted Conversion Price.

4.3.3 Effect of Conversion. All shares of Preferred Stock which shall have been surrendered for conversion as herein provided shall no longer be deemed to be outstanding and all rights with respect to such shares shall immediately cease and terminate at the Conversion Time, except only the right of the holders thereof to receive shares of Common Stock in exchange therefor, to receive payment in lieu of any fraction of a share otherwise issuable upon such conversion as provided in Subsection 4.2 and to receive payment of any dividends declared but unpaid thereon. Any shares of Preferred Stock so converted shall be retired and cancelled and may not be reissued as shares of such series, and the Corporation may thereafter take such appropriate action (without the need for stockholder action) as may be necessary to reduce the authorized number of shares of Preferred Stock accordingly.

4.3.4 No Further Adjustment. Upon any such conversion, no adjustment to the Conversion Price shall be made for any declared but unpaid dividends on the Preferred Stock surrendered for conversion or on the Common Stock delivered upon conversion.

4.3.5 Taxes. The Corporation shall pay any and all issue and other similar taxes that may be payable in respect of any issuance or delivery of shares of Common Stock upon conversion of shares of Preferred Stock pursuant to this Section 4. The Corporation shall not, however, be required to pay any tax which may be payable in respect of any transfer involved in the issuance and delivery of shares of Common Stock in a name other than that in which the shares of Preferred Stock so converted were registered, and no such issuance or delivery shall be made unless and until the person or entity requesting such issuance has paid to the Corporation the amount of any such tax or has established, to the satisfaction of the Corporation, that such tax has been paid.

4.4 Adjustments to Conversion Price for Diluting Issues.

4.4.1 Special Definitions. For purposes of this Article Fourth, the following definitions shall apply:

(a) “Additional Shares of Common Stock” shall mean all shares of Common Stock issued (or, pursuant to Subsection 4.4.3 below, deemed to be issued) by the Corporation after the Filing Date, other than (1) the following shares of Common Stock and (2) shares of Common Stock deemed issued pursuant to the following Options and Convertible Securities (clauses (1) and (2), collectively, “Exempted Securities”):

(i) shares of Common Stock issued upon conversion of Preferred Stock as converted pursuant to this Certificate of Incorporation;

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(ii) shares of Common Stock, Options or Convertible Securities issued as a dividend or distribution on Preferred Stock;

(iii) shares of Common Stock, Options or Convertible Securities issued by reason of a dividend, stock split, split-up or other distribution on shares of Common Stock that is covered by Subsection 4.5, 4.6, 4.7, or 4.8;

(iv) shares of Common Stock or Options issued to employees or directors of, or consultants or advisors to, the Corporation or any of its subsidiaries pursuant to a plan, agreement or arrangement approved by a majority of the Board of Directors of the Corporation, including the approval of the Requisite Directors (so long as all directors have received prior notice of such action);

(v) shares of Common Stock or Convertible Securities actually issued upon the exercise of Options or shares of Common Stock actually issued upon the conversion or exchange of Convertible Securities, in each case provided such issuance is pursuant to the terms of such Option or Convertible Security and each such issuance is approved by a majority of the Board of Directors of the Corporation, including the approval of the Requisite Directors (so long as all directors have received prior notice of such action);

(vi) shares of Common Stock, Options or Convertible Securities issued to banks, equipment lessors or other financial institutions, or to real property lessors, pursuant to a debt financing, equipment leasing or real property leasing transaction approved by a majority of the Board of Directors of the Corporation, including the approval of the Requisite Directors (so long as all directors have received prior notice of such action);

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(vii) shares of Common Stock, Options or Convertible Securities issued pursuant to the acquisition of another corporation by the Corporation by merger, purchase of substantially all of the assets or other reorganization, provided, that such issuances are approved by a majority of the Board of Directors of the Corporation, including the approval of the Requisite Directors (so long as all directors have received prior notice of such action); or

(viii) shares of Common Stock, Options or Convertible Securities issued in connection with sponsored research, collaboration, technology license, development, marketing or strategic partnerships approved by a majority of the Board of Directors of the Corporation, including the approval of the Requisite Directors (so long as all directors have received prior notice of such action).

(b) “Convertible Securities” shall mean any evidences of indebtedness, shares or other securities directly or indirectly convertible into or exchangeable for Common Stock, but excluding Options.

(c) “Filing Date” shall mean the date on which this Fifth Amended and Restated Certificate of Incorporation was filed with the Secretary of State for the State of Delaware.

(d) “Option” shall mean rights, options or warrants, to subscribe for, purchase or otherwise acquire Common Stock or Convertible Securities.

4.4.2 No Adjustment of Conversion Price. No adjustment in the Conversion Price of the Series A Preferred Stock or Series B Preferred Stock shall be made as the result of the issuance or deemed issuance of Additional Shares of Common Stock if the Corporation receives written notice from the Requisite Holders agreeing that no such adjustment shall be made as the result of the issuance or deemed issuance of such Additional Shares of Common Stock. No adjustment in the Conversion Price of the Series C Preferred Stock shall be made as the result of the issuance or deemed issuance of Additional Shares of Common Stock if the Corporation receives written notice from the Series C Majority agreeing that no such adjustment shall be made as the result of the issuance or deemed issuance of such Additional Shares of Common Stock.

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4.4.3 Deemed Issue of Additional Shares of Common Stock.

(a) If the Corporation at any time or from time to time after the Filing Date shall issue any Options or Convertible Securities (excluding Options or Convertible Securities which are themselves Exempted Securities) or shall fix a record date for the determination of holders of any class of securities entitled to receive any such Options or Convertible Securities, then the maximum number of shares of Common Stock (as set forth in the instrument relating thereto, assuming the satisfaction of any conditions to exercisability, convertibility or exchangeability but without regard to any provision contained therein for a subsequent adjustment of such number) issuable upon the exercise of such Options or, in the case of Convertible Securities and Options therefor, the conversion or exchange of such Convertible Securities, shall be deemed to be Additional Shares of Common Stock issued as of the time of such issue or, in case such a record date shall have been fixed, as of the close of business on such record date.

(b) If the terms of any Option or Convertible Security, the issuance of which resulted in an adjustment to the Conversion Price pursuant to the terms of Subsection 4.4.4, are revised as a result of an amendment to such terms or any other adjustment pursuant to the provisions of such Option or Convertible Security (but excluding automatic adjustments to such terms pursuant to anti-dilution or similar provisions of such Option or Convertible Security) to provide for either (1) any increase or decrease in the number of shares of Common Stock issuable upon the exercise, conversion and/or exchange of any such Option or Convertible Security or (2) any increase or decrease in the consideration payable to the Corporation upon such exercise, conversion and/or exchange, then, effective upon such increase or decrease becoming effective, the Conversion Price computed upon the original issue of such Option or Convertible Security (or upon the occurrence of a record date with respect thereto) shall be readjusted to such Conversion Price as would have obtained had such revised terms been in effect upon the original date of issuance of such Option or Convertible Security. Notwithstanding the foregoing, no readjustment pursuant to this clause (b) shall have the effect of increasing the Conversion Price to an amount which exceeds the lower of (i) the Conversion Price in effect immediately prior to the original adjustment made as a result of the issuance of such Option or Convertible Security, or (ii) the Conversion Price that would have resulted from any issuances of Additional Shares of Common Stock (other than deemed issuances of Additional Shares of Common Stock as a result of the issuance of such Option or Convertible Security) between the original adjustment date and such readjustment date.

(c) If the terms of any Option or Convertible Security (excluding Options or Convertible Securities which are themselves Exempted Securities), the issuance of which did not result in an adjustment to the Conversion Price pursuant to the terms of Subsection 4.4.4 (either because the consideration per share (determined pursuant to Subsection 4.4.5) of the Additional Shares of Common Stock subject thereto was equal to or greater than the Conversion Price then in effect, or because such Option or Convertible Security was issued before the Filing Date), are revised after the Filing Date as a result of an amendment to such terms or any other adjustment pursuant to the provisions of such Option or Convertible Security (but excluding automatic adjustments to such terms pursuant to anti-dilution or similar provisions of such Option or Convertible Security) to provide for either (1) any increase in the number of shares of Common Stock issuable upon the exercise, conversion or exchange of any such Option or Convertible

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Security or (2) any decrease in the consideration payable to the Corporation upon such exercise, conversion or exchange, then such Option or Convertible Security, as so amended or adjusted, and the Additional Shares of Common Stock subject thereto (determined in the manner provided in Subsection 4.4.3(a)) shall be deemed to have been issued effective upon such increase or decrease becoming effective.

(d) Upon the expiration or termination of any unexercised Option or unconverted or unexchanged Convertible Security (or portion thereof) which resulted (either upon its original issuance or upon a revision of its terms) in an adjustment to the Conversion Price pursuant to the terms of Subsection 4.4.4, the Conversion Price shall be readjusted to such Conversion Price as would have obtained had such Option or Convertible Security (or portion thereof) never been issued.

(e) If the number of shares of Common Stock issuable upon the exercise, conversion and/or exchange of any Option or Convertible Security, or the consideration payable to the Corporation upon such exercise, conversion and/or exchange, is calculable at the time such Option or Convertible Security is issued or amended but is subject to adjustment based upon subsequent events, any adjustment to the Conversion Price provided for in this Subsection 4.4.3 shall be effected at the time of such issuance or amendment based on such number of shares or amount of consideration without regard to any provisions for subsequent adjustments (and any subsequent adjustments shall be treated as provided in clauses (b) and (c) of this Subsection 4.4.3). If the number of shares of Common Stock issuable upon the exercise, conversion and/or exchange of any Option or Convertible Security, or the consideration payable to the Corporation upon such exercise, conversion and/or exchange, cannot be calculated at all at the time such Option or Convertible Security is issued or amended, any adjustment to the Conversion Price that would result under the terms of this Subsection 4.4.3 at the time of such issuance or amendment shall instead be effected at the time such number of shares and/or amount of consideration is first calculable (even if subject to subsequent adjustments), assuming for purposes of calculating such adjustment to the Conversion Price that such issuance or amendment took place at the time such calculation can first be made.

4.4.4 Adjustment of Conversion Price Upon Issuance of Additional Shares of Common Stock. In the event the Corporation shall at any time after the Filing Date issue Additional Shares of Common Stock (including Additional Shares of Common Stock deemed to be issued pursuant to Subsection 4.4.3), without consideration or for a consideration per share less than the Conversion Price in effect immediately prior to such issue, then the Conversion Price shall be reduced, concurrently with such issue, to a price (calculated to the nearest one-hundredth of a cent) determined in accordance with the following formula:

CP₂ = CP₁* (A+ B) / (A+ C).

For purposes of the foregoing formula, the following definitions shall apply:

(a) “CP₂” shall mean the Conversion Price in effect immediately after such issue of Additional Shares of Common Stock

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(b) “CP₁” shall mean the Conversion Price in effect immediately prior to such issue of Additional Shares of Common Stock;

(c) “A” shall mean the number of shares of Common Stock outstanding immediately prior to such issue of Additional Shares of Common Stock (treating for this purpose as outstanding all shares of Common Stock issuable upon exercise of Options outstanding immediately prior to such issue or upon conversion or exchange of Convertible Securities (including the Preferred Stock) outstanding (assuming exercise of any outstanding Options therefor) immediately prior to such issue);

(d) “B” shall mean the number of shares of Common Stock that would have been issued if such Additional Shares of Common Stock had been issued at a price per share equal to CP₁ (determined by dividing the aggregate consideration received by the Corporation in respect of such issue by CP₁); and

(e) “C” shall mean the number of such Additional Shares of Common Stock issued in such transaction.

4.4.5 Determination of Consideration. For purposes of this Subsection 4.4, the consideration received by the Corporation for the issue of any Additional Shares of Common Stock shall be computed as follows:

(a) Cash and Property: Such consideration shall:

(i) insofar as it consists of cash, be computed at the aggregate amount of cash received by the Corporation, excluding amounts paid or payable for accrued interest;

(ii) insofar as it consists of property other than cash, be computed at the fair market value thereof at the time of such issue, as determined in good faith by the Board of Directors of the Corporation; and

(iii) in the event Additional Shares of Common Stock are issued together with other shares or securities or other assets of the Corporation for consideration which covers both, be the proportion of such consideration so received, computed as provided in clauses (i) and (ii) above, as determined in good faith by the Board of Directors of the Corporation.

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(b) Options and Convertible Securities. The consideration per share received by the Corporation for Additional Shares of Common Stock deemed to have been issued pursuant to Subsection 4.4.3, relating to Options and Convertible Securities, shall be determined by dividing

(i) the total amount, if any, received or receivable by the Corporation as consideration for the issue of such Options or Convertible Securities, plus the minimum aggregate amount of additional consideration (as set forth in the instruments relating thereto, without regard to any provision contained therein for a subsequent adjustment of such consideration) payable to the Corporation upon the exercise of such Options or the conversion or exchange of such Convertible Securities, or in the case of Options for Convertible Securities, the exercise of such Options for Convertible Securities and the conversion or exchange of such Convertible Securities, by

(ii) the maximum number of shares of Common Stock (as set forth in the instruments relating thereto, without regard to any provision contained therein for a subsequent adjustment of such number) issuable upon the exercise of such Options or the conversion or exchange of such Convertible Securities, or in the case of Options for Convertible Securities, the exercise of such Options for Convertible Securities and the conversion or exchange of such Convertible Securities.

4.4.6 Multiple Closing Dates. In the event the Corporation shall issue on more than one (1) date Additional Shares of Common Stock that are a part of one (1) transaction or a series of related transactions and that would result in an adjustment to the Conversion Price pursuant to the terms of Subsection 4.4.4, and such issuance dates occur within a period of no more than thirty (30) days from the first such issuance to the final such issuance, then, upon the final such issuance, the Conversion Price shall be readjusted to give effect to all such issuances as if they occurred on the date of the first such issuance (and without giving effect to any additional adjustments as a result of any such subsequent issuances within such period).

4.5 Adjustment for Stock Splits and Combinations. If the Corporation shall at any time or from time to time after the Filing Date effect a subdivision of the outstanding Common Stock, the Conversion Price in effect immediately before that subdivision shall be proportionately decreased so that the number of shares of Common Stock issuable on conversion of each share of such series shall be increased in proportion to such increase in the aggregate number of shares of Common Stock outstanding. If the Corporation shall at any time or from time to time after the Filing Date combine the outstanding shares of Common Stock, the Conversion Price in effect immediately before the combination shall be proportionately increased so that the number of shares of Common Stock issuable on conversion of each share of such series shall be decreased in proportion to such decrease in the aggregate number of shares of Common Stock outstanding. Any adjustment under this subsection shall become effective at the close of business on the date the subdivision or combination becomes effective.

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4.6 Adjustment for Certain Dividends and Distributions. In the event the Corporation at any time or from time to time after the Filing Date shall make or issue, or fix a record date for the determination of holders of Common Stock entitled to receive, a dividend or other distribution payable on the Common Stock in additional shares of Common Stock, then and in each such event the Conversion Price in effect immediately before such event shall be decreased as of the time of such issuance or, in the event such a record date shall have been fixed, as of the close of business on such record date, by multiplying the Conversion Price then in effect by a fraction:

(1) the numerator of which shall be the total number of shares of Common Stock issued and outstanding immediately prior to the time of such issuance or the close of business on such record date, and

(2) the denominator of which shall be the total number of shares of Common Stock issued and outstanding immediately prior to the time of such issuance or the close of business on such record date plus the number of shares of Common Stock issuable in payment of such dividend or distribution.

Notwithstanding the foregoing, (a) if such record date shall have been fixed and such dividend is not fully paid or if such distribution is not fully made on the date fixed therefor, the Conversion Price shall be recomputed accordingly as of the close of business on such record date and thereafter the Conversion Price shall be adjusted pursuant to this subsection as of the time of actual payment of such dividends or distributions; and (b) that no such adjustment shall be made if the holders of Preferred Stock simultaneously receive a dividend or other distribution of shares of Common Stock in a number equal to the number of shares of Common Stock as they would have received if all outstanding shares of Preferred Stock had been converted into Common Stock on the date of such event.

4.7 Adjustments for Other Dividends and Distributions. In the event the Corporation at any time or from time to time after the Filing Date shall make or issue, or fix a record date for the determination of holders of Common Stock entitled to receive, a dividend or other distribution payable in securities of the Corporation (other than a distribution of shares of Common Stock in respect of outstanding shares of Common Stock) or in other property and the provisions of Section 1 do not apply to such dividend or distribution, then and in each such event the holders of Preferred Stock shall receive, simultaneously with the distribution to the holders of Common Stock, a dividend or other distribution of such securities or other property in an amount equal to the amount of such securities or other property as they would have received if all outstanding shares of Preferred Stock had been converted into Common Stock on the date of such event.

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4.8 Adjustment for Merger or Reorganization, etc. Subject to the provisions of Subsection 2.3, if there shall occur any reorganization, recapitalization, reclassification, consolidation or merger involving the Corporation in which the Common Stock (but not the Preferred Stock) is converted into or exchanged for securities, cash or other property (other than a transaction covered by Subsections 4.4, 4.6 or 4.7), then, following any such reorganization, recapitalization, reclassification, consolidation or merger, each share of Preferred Stock shall thereafter be convertible in lieu of the Common Stock into which it was convertible prior to such event into the kind and amount of securities, cash or other property which a holder of the number of shares of Common Stock of the Corporation issuable upon conversion of one (1) share of Preferred Stock immediately prior to such reorganization, recapitalization, reclassification, consolidation or merger would have been entitled to receive pursuant to such transaction; and, in such case, appropriate adjustment (as determined in good faith by the Board of Directors of the Corporation) shall be made in the application of the provisions in this Section 4 with respect to the rights and interests thereafter of the holders of the Preferred Stock, to the end that the provisions set forth in this Section 4 (including provisions with respect to changes in and other adjustments of the Conversion Price) shall thereafter be applicable, as nearly as reasonably may be, in relation to any securities or other property thereafter deliverable upon the conversion of the Preferred Stock.

4.9 Certificate as to Adjustments. Upon the occurrence of each adjustment or readjustment of the Conversion Price pursuant to this Section 4, the Corporation at its expense shall, as promptly as reasonably practicable but in any event not later than ten (10) days thereafter, compute such adjustment or readjustment in accordance with the terms hereof and furnish to each holder of Preferred Stock a certificate setting forth such adjustment or readjustment (including the kind and amount of securities, cash or other property into which the Preferred Stock is convertible) and showing in detail the facts upon which such adjustment or readjustment is based. The Corporation shall, as promptly as reasonably practicable after the written request at any time of any holder of Preferred Stock (but in any event not later than ten (10) days thereafter), furnish or cause to be furnished to such holder a certificate setting forth (i) the Conversion Price then in effect, and (ii) the number of shares of Common Stock and the amount, if any, of other securities, cash or property which then would be received upon the conversion of Preferred Stock.

4.10 Notice of Record Date. In the event:

(a) the Corporation shall take a record of the holders of its Common Stock (or other capital stock or securities at the time issuable upon conversion of the Preferred Stock) for the purpose of entitling or enabling them to receive any dividend or other distribution, or to receive any right to subscribe for or purchase any shares of capital stock of any class or any other securities, or to receive any other security; or

(b) of any capital reorganization of the Corporation, any reclassification of the Common Stock of the Corporation, or any Deemed Liquidation Event; or

(c) of the voluntary or involuntary dissolution, liquidation or winding-up of the Corporation,

then, and in each such case, the Corporation will send or cause to be sent to the holders of the Preferred Stock a notice specifying, as the case may be, (i) the record date for such dividend, distribution or right, and the amount and character of such dividend, distribution or right, or (ii)

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the effective date on which such reorganization, reclassification, consolidation, merger, transfer, dissolution, liquidation or winding-up is proposed to take place, and the time, if any is to be fixed, as of which the holders of record of Common Stock (or such other capital stock or securities at the time issuable upon the conversion of the Preferred Stock) shall be entitled to exchange their shares of Common Stock (or such other capital stock or securities) for securities or other property deliverable upon such reorganization, reclassification, consolidation, merger, transfer, dissolution, liquidation or winding-up, and the amount per share and character of such exchange applicable to the Preferred Stock and the Common Stock, such notice shall be sent at least ten (10) days prior to the record date or effective date for the event specified in such notice.

5. Mandatory Conversion.

5.1 Trigger Events. Upon either (a) the closing of the sale of shares of Common Stock to the public in a firm-commitment underwritten public offering pursuant to an effective registration statement under the Securities Act of 1933, as amended, resulting in at least $50,000,000 of gross proceeds to the Corporation and the Corporation’s shares having been listed for trading on the New York Stock Exchange, NASDAQ Global Select Market or NASDAQ Global Market (a “Qualified IPO”) or (b) the date and time, or the occurrence of an event, specified by vote or written consent of the Requisite Holders (the time of such closing or the date and time specified or the time of the event specified in such vote or written consent is referred to herein as the “Mandatory Conversion Time”), (i) all outstanding shares of Preferred Stock shall automatically be converted into shares of Common Stock, at the then effective Conversion Ratio and (ii) such shares may not be reissued by the Corporation; provided, that the outstanding shares of Series C Preferred Stock shall not be converted into shares of Common Stock pursuant to clause (b) of this Subsection 5.1 without the vote or written consent of the Series C Majority.

5.2 Procedural Requirements. All holders of record of shares of Preferred Stock shall be sent written notice of the Mandatory Conversion Time and the place designated for mandatory conversion of all such shares of Preferred Stock pursuant to this Section 5. Such notice need not be sent in advance of the occurrence of the Mandatory Conversion Time. Upon receipt of such notice, each holder of shares of Preferred Stock shall surrender his, her or its certificate or certificates for all such shares (or, if such holder alleges that such certificate has been lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably acceptable to the Corporation to indemnify the Corporation against any claim that may be made against the Corporation on account of the alleged loss, theft or destruction of such certificate) to the Corporation at the place designated in such notice. If so required by the Corporation, certificates surrendered for conversion shall be endorsed or accompanied by written instrument or instruments of transfer, in form satisfactory to the Corporation, duly executed by the registered holder or by his, her or its attorney duly authorized in writing. All rights with respect to the Preferred Stock converted pursuant to Subsection 5.1, including the rights, if any, to receive notices and vote (other than as a holder of Common Stock), will terminate at the Mandatory Conversion Time (notwithstanding the failure of the holder or holders thereof to surrender the certificates at or prior to such time), except only the rights of the holders thereof, upon surrender of their certificate or certificates (or lost certificate affidavit and agreement) therefor, to receive the items provided for in the next sentence of this Subsection 5.2. As soon as practicable after the Mandatory Conversion Time and the surrender of the certificate or certificates (or lost certificate affidavit and agreement) for Preferred Stock, the Corporation shall issue and deliver to such holder, or to his, her or its

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nominees, a certificate or certificates for the number of full shares of Common Stock issuable on such conversion in accordance with the provisions hereof, together with cash as provided in Subsection 4.2 in lieu of any fraction of a share of Common Stock otherwise issuable upon such conversion and the payment of any declared but unpaid dividends on the shares of Preferred Stock converted. Such converted Preferred Stock shall be retired and cancelled and may not be reissued as shares of such series, and the Corporation may thereafter take such appropriate action (without the need for stockholder action) as may be necessary to reduce the authorized number of shares of Preferred Stock accordingly.

5A. Special Mandatory Conversion.

5A.1. Trigger Events. If a holder of Preferred Stock or Recent Common Shares (as hereinafter defined) is deemed a Defaulting Holder, then notwithstanding any other provision of this Certificate of Incorporation, (i) all shares of Preferred Stock, if any, then held by such Defaulting Holder shall automatically, and without any further action on the part of such holder(s) be converted into shares of Common Stock at a ratio of 1/10th of the applicable Conversion Ratio in effect immediately prior to the Mandatory Conversion Date and (ii) all Recent Common Shares, if any, then held by such Defaulting Holder shall automatically, and without any further action on the part of such holder(s) be converted into a lesser number of shares of Common Stock that would have been issued had the Recently Converted Preferred Shares be converted into shares of Common Stock at a ratio of 1/10th of the applicable Conversion Ratio in effect immediately prior to the Mandatory Conversion Date that would be applicable if the Recently Converted Preferred Shares had not been voluntarily converted in each case, effective upon, subject to, and concurrently with the Mandatory Conversion Date. The conversion(s) pursuant to this Subsection 5A.1 is referred to as a “Special Mandatory Conversion.” Notwithstanding the foregoing, no Special Mandatory Conversion shall occur at any time following a Deemed Liquidation Event or Qualified IPO.

5A.2. Procedural Requirements. Within five (5) business days after the consummation of a Special Mandatory Conversion, each holder of Preferred Stock and Recent Common Shares that are converted pursuant to Subsection 5A.1 (the “Default Conversion Shares”) shall be sent written notice of such Special Mandatory Conversion and the place designated for mandatory conversion of all such Default Conversion Shares pursuant to this Section 5A. Upon receipt of such notice, each holder of such shares of Default Conversion Shares in certificated form shall surrender his, her or its certificate or certificates for all such shares (or, if such holder alleges that any such certificate has been lost, stolen or destroyed, a lost certificate affidavit and agreement reasonably acceptable to the Corporation to indemnify the Corporation against any claim that may be made against the Corporation on account of the alleged loss, theft or destruction of such certificate) to the Corporation at the place designated in such notice. If so required by the Corporation, any certificates surrendered for conversion shall be endorsed or accompanied by written instrument or instruments of transfer, in form satisfactory to the Corporation, duly executed by the registered holder or by his, her or its attorney duly authorized in writing. All rights with respect to the Preferred Stock converted pursuant to Subsection 5A.1, including the rights, if any, to receive notices and vote (other than as a holder of Common Stock and any lock-up or market standoff agreement in connection with the Corporation’s initial public offering), will terminate at the time of the Special Mandatory Conversion (notwithstanding the failure of the holder or holders thereof to surrender any certificates for such shares at or prior to

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such time), except only the rights of the holders thereof, upon surrender of any certificate or certificates of such holders therefor (or lost certificate affidavit and agreement), to receive the items provided for in the next sentence of this Subsection 5A.2. As soon as practicable after the Special Mandatory Conversion and, if applicable, the surrender of any certificate or certificates (or lost certificate affidavit and agreement) for Preferred Stock so converted, the Corporation shall (a) issue and deliver to such holder, or to his, her or its nominees, a certificate or certificates for the number of full shares of Common Stock issuable on such conversion in accordance with the provisions hereof and (b) pay cash as provided in Subsection 4.2 in lieu of any fraction of a share of Common Stock otherwise issuable upon such conversion and the payment of any declared but unpaid dividends on the shares of Preferred Stock converted. Such converted Preferred Stock shall be retired and cancelled and may not be reissued as shares of such series, and the Corporation may thereafter take such appropriate action (without the need for stockholder action) as may be necessary to reduce the authorized number of shares of Preferred Stock accordingly.

5A.3. Definitions. For purposes of this Section 5A, the following definitions shall apply:

“Affiliate” shall mean, with respect to any holder of shares of Preferred Stock, any person, entity or firm which, directly or indirectly, controls, is controlled by or is under common control with such holder, including, without limitation, any entity of which the holder is a partner or member, any partner, officer, director, member or employee of such holder and any venture capital fund or other investment fund now or hereafter existing of which the holder is a partner or member which is controlled by or under common control with one (1) or more general partners of such holder or shares the same management company or investment advisor with such holder.

“CFIUS” means the Committee on Foreign Investment in the United States, or any member agency thereof acting in such capacity.

“CFIUS Satisfied Condition” means (a) the filing holder and the Corporation shall have received written notice from CFIUS stating that: (i) CFIUS has concluded that the Covered Transactions do not constitute a “covered transaction” subject to review under the DPA; or (ii) the assessment, review or investigation of the Covered Transactions under the DPA has concluded, and there are no unresolved national security concerns with respect to the Covered Transactions; (b) CFIUS has sent a report to the President of the United States requesting the President’s decision with respect to the Covered Transactions and either (i) the period under the DPA subsequent to the President’s receipt of the CFIUS report during which the President may announce his decision to take action to suspend, prohibit or place any limitations on the Covered Transactions has expired without any such action being taken and without that Presidential review having been suspended or (ii) the President of the United States has announced a decision not to take any action to suspend, prohibit or place any limitations on the Covered Transactions; or (c) CFIUS has provided written notice that it is not able to complete action under the DPA with respect to the Covered Transactions on the basis of a CFIUS declaration, but CFIUS has not requested that the filing holder and the Corporation submit a CFIUS notice and has not initiated a unilateral CFIUS review, and the filing holder deems such circumstances to constitute the CFIUS Satisfied Condition.

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“Defaulting Holder” shall mean any Key Investor that does not purchase its Pro Rata Portion of the securities sold in a Qualified Future Financing and its Affiliates; provided, that (a) if and only if (i) CFIUS requests or requires that such holder or the Corporation file a notice or declaration with CFIUS pursuant to the DPA with respect to a Qualified Future Financing (the “Covered Transactions”) or (ii) such holder or the Corporation determines that a filing with CFIUS with respect to the Covered Transactions is advisable or required by applicable law (each of (i) and (ii), a “CFIUS Filing Requirement”), then in either case of a CFIUS Filing Requirement, such holder shall not be obligated to participate in the Qualified Future Financing until the CFIUS Satisfied Condition shall have been achieved and shall not be deemed a “Defaulting Holder” unless such holder does not purchase its Pro Rata Portion of the securities sold or to be sold in a Qualified Future Financing within ten (10) business days after the receipt of the CFIUS Satisfied Condition and (b) any Affiliate of a Key Investor may purchase such Key Investor’s Pro Rata Portion of the securities sold in a Qualified Future Financing and such purchase shall be deemed a purchase by the Key Investor for the purpose of this Section. For the avoidance of doubt, such holder shall not have any obligation to accept or take any action, condition or restriction with respect to the Covered Transactions in order to achieve the CFIUS Satisfied Condition.

“DPA” means Section 721 of the Defense Production Act of 1950, as amended (50 U.S.C. § 4565), and all rules and regulations thereunder, including as codified at 31 C.F.R. Parts 800 and 801.

“Fully Diluted Capitalization” shall mean the number of shares of Common Stock outstanding and deemed outstanding (treating for this purpose as outstanding all shares of Common Stock issuable upon exercise of awards authorized for issuance under the Corporation’s Stock Plan (as defined in the Series C Purchase Agreement) and upon exercise or conversion of all outstanding options, warrants and other equity securities convertible into Common Stock, including the Preferred Stock and Convertible Securities).

“Investors’ Rights Agreement” shall mean that certain Second Amended and Restated Investors’ Rights Agreement, dated on or about the date hereof, by and among the Corporation and the other parties thereto.

“Key Investor” shall mean any holder of shares of Preferred Stock set forth on Schedule B of the Investors’ Rights Agreement that holds, either directly or through an Affiliate, shares of Preferred Stock representing at least 1.50% of the Corporation’s Fully Diluted Capitalization immediately prior to a Qualified Future Financing.

“Mandatory Conversion Date” shall mean the closing date of the Qualified Future Financing.

“Pro Rata Portion” shall mean that portion of such shares that equals the proportion of that total number of shares of Preferred Stock then held by such holder bears to the total number of shares of capital stock of the Corporation then outstanding (assuming the conversion or exercise of all convertible and exercisable securities), multiplied by the number of shares allocated by the Board of Directors to existing investors for such financing.

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“Qualified Future Financing” means a bona fide equity or debt financing transaction or series of transactions consummated after the Initial Closing (as defined in the Series C Purchase Agreement) that is approved by the Corporation’s Board of Directors, including the Requisite Directors, whereby the Corporation issues any equity security, or any convertible note, simple agreement for future equity or similar convertible instrument that is convertible into an equity security, at a price per share equal to or less than the Original Issue Price for the Series C Preferred Stock.

“Recent Common Shares” shall mean any Common Stock held by a Defaulting Holder or its Affiliates on a Mandatory Conversion Date that was issued as a result of any voluntary conversion of Preferred Stock by a holder (or its Affiliate, as applicable) pursuant to Section 4 after the date that is one hundred and twenty (120) days prior to the closing date of the Qualified Future Financing.

“Recently Converted Preferred Shares” shall mean the Preferred Stock that was converted into Recent Common Shares.

“Series C Purchase Agreement” shall mean that certain Series C Preferred Stock Purchase Agreement, dated on or about the date hereof, by and among the Corporation and the other parties thereto.

6. Redeemed or Otherwise Acquired Shares. Any shares of Preferred Stock that are redeemed or otherwise acquired by the Corporation or any of its subsidiaries shall be automatically and immediately cancelled and retired and shall not be reissued, sold or transferred. Neither the Corporation nor any of its subsidiaries may exercise any voting or other rights granted to the holders of Preferred Stock following redemption.

7. Waiver. Except as otherwise set forth herein, any of the rights, powers, preferences and other terms of the Preferred Stock set forth herein may be waived on behalf of all holders of Preferred Stock by the written consent or affirmative vote of the Requisite Holders.

8. Notices. Any notice required or permitted by the provisions of this Article Fourth to be given to a holder of shares of Preferred Stock shall be mailed, postage prepaid, to the post office address last shown on the records of the Corporation, or given by electronic communication in compliance with the provisions of the General Corporation Law, and shall be deemed sent upon such mailing or electronic transmission.

FIFTH: Subject to any additional vote required by the Certificate of Incorporation or Bylaws, in furtherance and not in limitation of the powers conferred by statute, the Board of Directors is expressly authorized to make, repeal, alter, amend and rescind any or all of the Bylaws of the Corporation.

SIXTH: Subject to any additional vote required by the Certificate of Incorporation, the number of directors of the Corporation shall be determined in the manner set forth in the Bylaws of the Corporation.

SEVENTH: Elections of directors need not be by written ballot unless the Bylaws of the Corporation shall so provide.

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EIGHTH: Meetings of stockholders may be held within or without the State of Delaware, as the Bylaws of the Corporation may provide. The books of the Corporation may be kept outside the State of Delaware at such place or places as may be designated from time to time by the Board of Directors or in the Bylaws of the Corporation.

NINTH: To the fullest extent permitted by law, a director of the Corporation shall not be personally liable to the Corporation or its stockholders for monetary damages for breach of fiduciary duty as a director. If the General Corporation Law or any other law of the State of Delaware is amended after approval by the stockholders of this Article Ninth to authorize corporate action further eliminating or limiting the personal liability of directors, then the liability of a director of the Corporation shall be eliminated or limited to the fullest extent permitted by the General Corporation Law as so amended.

Any repeal or modification of the foregoing provisions of this Article Ninth by the stockholders of the Corporation shall not adversely affect any right or protection of a director of the Corporation existing at the time of, or increase the liability of any director of the Corporation with respect to any acts or omissions of such director occurring prior to, such repeal or modification.

TENTH: To the fullest extent permitted by applicable law, the Corporation is authorized to provide indemnification of (and advancement of expenses to) directors, officers and agents of the Corporation (and any other persons to which General Corporation Law permits the Corporation to provide indemnification) through Bylaw provisions, agreements with such agents or other persons, vote of stockholders or disinterested directors or otherwise, in excess of the indemnification and advancement otherwise permitted by Section 145 of the General Corporation Law.

Any amendment, repeal or modification of the foregoing provisions of this Article Tenth shall not (a) adversely affect any right or protection of any director, officer or other agent of the Corporation existing at the time of such amendment, repeal or modification or (b) increase the liability of any director of the Corporation with respect to any acts or omissions of such director, officer or agent occurring prior to, such amendment, repeal or modification.

ELEVENTH: The Corporation renounces, to the fullest extent permitted by law, any interest or expectancy of the Corporation in, or in being offered an opportunity to participate in, any Excluded Opportunity. An “Excluded Opportunity” is any matter, transaction or interest that is presented to, or acquired, created or developed by, or which otherwise comes into the possession of, (i) any director of the Corporation who is not an employee of the Corporation or any of its subsidiaries, or (ii) any holder of Preferred Stock or any partner, member, director, stockholder, employee, affiliate or agent of any such holder, other than someone who is an employee of the Corporation or any of its subsidiaries (collectively, the persons referred to in clauses (i) and (ii) are “Covered Persons”), unless such matter, transaction or interest is presented to, or acquired, created or developed by, or otherwise comes into the possession of, a Covered Person expressly and solely in such Covered Person’s capacity as a director of the Corporation while such Covered Person is performing services in such capacity. Any repeal or modification of this Article Eleventh will only be prospective and will not affect the rights under this Article Eleventh in effect at the time of the occurrence of any actions or omissions to act giving rise to liability. Notwithstanding anything to the contrary contained elsewhere in this Certificate of Incorporation, the affirmative vote of the Requisite Holders will be required to amend or repeal, or to adopt any provisions inconsistent with this Article Eleventh.

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TWELFTH: Unless the Corporation consents in writing to the selection of an alternative forum, the Court of Chancery in the State of Delaware shall be the sole and exclusive forum for any stockholder (including a beneficial owner) to bring (i) any derivative action or proceeding brought on behalf of the Corporation, (ii) any action asserting a claim of breach of fiduciary duty owed by any director, officer or other employee of the Corporation to the Corporation or the Corporation’s stockholders, (iii) any action asserting a claim against the Corporation, its directors, officers or employees arising pursuant to any provision of the Delaware General Corporation Law or the Corporation’s certificate of incorporation or bylaws or (iv) any action asserting a claim against the Corporation, its directors, officers or employees governed by the internal affairs doctrine, except for, as to each of (i) through (iv) above, any claim as to which the Court of Chancery determines that there is an indispensable party not subject to the jurisdiction of the Court of Chancery (and the indispensable party does not consent to the personal jurisdiction of the Court of Chancery within ten (10) days following such determination), which is vested in the exclusive jurisdiction of a court or forum other than the Court of Chancery, or for which the Court of Chancery does not have subject matter jurisdiction. If any provision or provisions of this Article Twelfth shall be held to be invalid, illegal or unenforceable as applied to any person or entity or circumstance for any reason whatsoever, then, to the fullest extent permitted by law, the validity, legality and enforceability of such provisions in any other circumstance and of the remaining provisions of this Article Twelfth (including, without limitation, each portion of any sentence of this Article Twelfth containing any such provision held to be invalid, illegal or unenforceable that is not itself held to be invalid, illegal or unenforceable) and the application of such provision to other persons or entities and circumstances shall not in any way be affected or impaired thereby.

3. That the foregoing amendment and restatement was approved by the holders of the requisite number of shares of this corporation in accordance with Section 228 of the General Corporation Law.

4. That this Fifth Amended and Restated Certificate of Incorporation, which restates and integrates and further amends the provisions of this Corporation’s Certificate of Incorporation, has been duly adopted in accordance with Sections 242 and 245 of the General Corporation Law.

[Remainder of Page Intentionally Left Blank]

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IN WITNESS WHEREOF, this Fifth Amended and Restated Certificate of Incorporation has been executed by a duly authorized officer of this corporation on this 5th day of February, 2021.

By:	/s/ Markus Renschler
	Name: Markus Renschler
	Title: President and CEO

[Signature Page to Fifth Amended and Restated Certificate of Incorporation]

EX-3.4

Exhibit 3.4

AMENDED AND RESTATED BY-LAWS OF

CYTEIR THERAPEUTICS, INC.

A DELAWARE CORPORATION

Dated: January 3, 2018

ARTICLE I – MEETINGS OF STOCKHOLDERS		1
SECTION 1.	PLACE OF MEETINGS	1
SECTION 2.	ANNUAL MEETING	1
SECTION 3.	SPECIAL MEETINGS	1
SECTION 4.	NOTICE OF MEETINGS	2
SECTION 5.	VOTING LIST	2
SECTION 6.	QUORUM	2
SECTION 7.	ADJOURNMENTS	2
SECTION 8.	ACTION AT MEETINGS	3
SECTION 9.	VOTING AND PROXIES	3
SECTION 10.	ACTION WITHOUT MEETING	3
ARTICLE II – DIRECTORS		4
SECTION 1.	NUMBER, ELECTION, TENURE AND QUALIFICATION	4
SECTION 2.	ENLARGEMENT	4
SECTION 3.	VACANCIES	4
SECTION 4.	RESIGNATION AND REMOVAL	4
SECTION 5.	GENERAL POWERS	5
SECTION 6.	CHAIRMAN OF THE BOARD	5
SECTION 7.	PLACE OF MEETINGS	5
SECTION 8.	REGULAR MEETINGS	5
SECTION 9.	SPECIAL MEETINGS	5
SECTION 10.	QUORUM, ACTION AT MEETING, ADJOURNMENTS	5
SECTION 11.	ACTION BY CONSENT	6
SECTION 12.	TELEPHONIC MEETINGS	6
SECTION 13.	COMMITTEES	6
SECTION 14.	COMPENSATION	6
ARTICLE III – OFFICERS		7
SECTION 1.	ENUMERATION	7
SECTION 2.	ELECTION	7
SECTION 3.	TENURE	7
SECTION 4.	PRESIDENT	7
SECTION 5.	VICE-PRESIDENTS	8
SECTION 6.	SECRETARY	8
SECTION 7.	ASSISTANT SECRETARIES	8
SECTION 8.	TREASURER	8
SECTION 9.	ASSISTANT TREASURERS	9
SECTION 10.	BOND	9
ARTICLE IV – NOTICES		9
SECTION 1.	DELIVERY	9
SECTION 2.	WAIVER OF NOTICE	9

ARTICLE V – INDEMNIFICATION		10
SECTION 1.	ACTIONS OTHER THAN BY OR IN THE RIGHT OF THE CORPORATION	10
SECTION 2.	ACTIONS BY OR IN THE RIGHT OF THE CORPORATION	10
SECTION 3.	SUCCESS ON THE MERITS	10
SECTION 4.	SPECIFIC AUTHORIZATION	11
SECTION 5.	ADVANCE PAYMENT	11
SECTION 6.	NON-EXCLUSIVITY	11
SECTION 7.	INSURANCE	11
SECTION 8.	CONTINUATION OF INDEMNIFICATION AND ADVANCEMENT OF EXPENSES	11
SECTION 9.	SEVERABILITY	11
SECTION 10.	INTENT OF ARTICLE	11
ARTICLE VI – CAPITAL STOCK		12
SECTION 1.	CERTIFICATES OF STOCK	12
SECTION 2.	LOST CERTIFICATES	12
SECTION 3.	TRANSFER OF STOCK; RESTRICTION ON TRANSFER	12
SECTION 4.	RECORD DATE	14
SECTION 5.	REGISTERED STOCKHOLDERS	15
ARTICLE VII – CERTAIN TRANSACTIONS		15
SECTION 1.	TRANSACTIONS WITH INTERESTED PARTIES	15
SECTION 2.	QUORUM	15
ARTICLE VIII – GENERAL PROVISIONS		16
SECTION 1.	DIVIDENDS	16
SECTION 2.	RESERVES	16
SECTION 3.	CHECKS	16
SECTION 4.	FISCAL YEAR	16
SECTION 5.	SEAL	16
ARTICLE IX – AMENDMENTS		16

ADDENDUM

Register of Amendments to the By-Laws

(ii)

* * * * *

AMENDED AND RESTATED BY-LAWS

* * * * *

ARTICLE I

MEETINGS OF STOCKHOLDERS

Section 1. Place of Meetings. All meetings of the stockholders may be held at such place within or without the State of Delaware as may be fixed from time to time by the Board of Directors or the Chief Executive Officer, or if not so designated, at the registered office of the Corporation. Notwithstanding the foregoing, the Board of Directors may, in its sole discretion, determine that the meeting shall not be held at any place, but may instead be held solely by means of remote communication as authorized by Section 211(a)(2) of the General Corporation Law of Delaware. If so authorized, and subject to such guidelines and procedures as the Board of Directors may adopt, stockholders and proxyholders not physically present at a meeting of stockholders may, by means of remote communication, participate in a meeting of stockholders whether such meeting is to be held at a designated place or solely by means of remote communication, provided that (i) the Corporation shall implement reasonable measures to verify that each person deemed present and permitted to vote at the meeting by means of remote communication is a stockholder or proxyholder, (ii) the Corporation shall implement reasonable measures to provide such stockholders and proxyholders a reasonable opportunity to participate in the meeting and to vote on matters submitted to the stockholders, including an opportunity to read or hear the proceedings of the meeting substantially concurrently with such proceedings, and (iii) if any stockholder or proxyholder votes or takes other action at the meeting by means of remote communication, a record of such vote or other action shall be maintained by the Corporation.

Section 2. Annual Meeting. Unless directors are elected by written consent in lieu of an annual meeting as permitted by law and these Amended and Restated By-Laws (the “By- laws”), an annual meeting of stockholders may be held at such date and time, and by such means of remote communication, if any, as shall be designated from time to time by the Board of Directors or the Chief Executive Officer, at which meeting the stockholders shall elect by a plurality vote a board of directors and shall transact such other business as may be properly brought before the meeting. If no annual meeting is held in accordance with the foregoing provisions, the Board of Directors shall cause the meeting to be held as soon thereafter as convenient, which meeting shall be designated a special meeting in lieu of annual meeting.

Section 3. Special Meetings. Special meetings of the stockholders, for any purpose or purposes, may, unless otherwise prescribed by statute or by the certificate of incorporation, be called by the Board of Directors or the Chief Executive Officer and shall be called by the Chief Executive Officer or Secretary at the request in writing of a majority of the Board of Directors, or at the request in writing of stockholders owning a majority in amount of the entire capital stock of the Corporation issued and outstanding and entitled to vote. Such request shall state the purpose or purposes of the proposed meeting. Business transacted at any special meeting shall be limited to matters relating to the purpose or purposes stated in the notice of meeting.

Section 4. Notice of Meetings. Except as otherwise provided by law, written notice of each meeting of stockholders, annual or special, stating the place, date and hour of the meeting, the means of remote communications, if any, by which stockholders and proxyholders may be deemed to be present in person and vote at such meeting and, in the case of a special meeting, the purpose or purposes for which the meeting is called, shall be given not less than ten (10) nor more than sixty (60) days before the date of the meeting, to each stockholder entitled to vote at such meeting.

Section 5. Voting List. The officer who has charge of the stock ledger of the Corporation shall prepare and make, at least ten (10) days before every meeting of stockholders, a complete list of the stockholders entitled to vote at the meeting, arranged in alphabetical order, and showing the address of each stockholder and the number of shares registered in the name of each stockholder. Such list shall be open to the examination of any stockholder, for any purpose germane to the meeting, during ordinary business hours, for a period of at least ten (10) days prior to the meeting, either (i) on a reasonably accessible electronic network, provided that the information required to gain access to such list is provided with the notice of the meeting, or (ii) at the Corporation’s principal place of business. In the event that the Corporation determines to make the list available on an electronic network, the Corporation may take reasonable steps to ensure that such information is available only to stockholders of the Corporation. If the meeting is to be held at a place, then the list shall be produced and kept at the time and place of the meeting during the whole time thereof, and may be inspected by any stockholder who is present. If the meeting is to be held solely by means of remote communication, then the list shall also be open to the examination of any stockholder during the whole time of the meeting on a reasonably accessible electronic network, and the information required to access such list shall be provided with the notice of the meeting.

Section 6. Quorum. The holders of a majority of the stock issued and outstanding and entitled to vote thereat, present in person or by remote communication, or represented by proxy, shall constitute a quorum at all meetings of the stockholders for the transaction of business, except as otherwise provided by statute, the certificate of incorporation or these By- Laws. Where a separate vote by a class or classes is required, one-third of the outstanding shares of such class or classes, present in person or by remote communication, or represented by proxy, shall constitute a quorum entitled to take action with respect to that vote on that matter. If no quorum shall be present or represented at any meeting of stockholders, such meeting may be adjourned in accordance with Section 7 hereof, until a quorum shall be present or represented.

Section 7. Adjournments. Any meeting of stockholders may be adjourned from time to time to any other time and to any other place at which a meeting of stockholders may be held under these By-Laws, which time and place shall be announced at the meeting, by a majority of the stockholders present in person or by remote communication, or represented by proxy at the meeting and entitled to vote (whether or not a quorum is present), or, if no stockholder is present or represented by proxy, by any officer entitled to preside at or to act as Secretary of such

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meeting, without notice other than announcement at the meeting. At such adjourned meeting, any business may be transacted which might have been transacted at the original meeting, provided that a quorum either was present at the original meeting or is present at the adjourned meeting. If the adjournment is for more than thirty days, or if after the adjournment a new record date is fixed for the adjourned meeting, a notice of the adjourned meeting shall be given to each stockholder of record entitled to vote at the meeting.

Section 8. Action at Meetings. When a quorum is present at any meeting, the affirmative vote of the holders of a majority of the stock present in person or by remote communication, or represented by proxy, entitled to vote and voting on the matter (or where a separate vote by a class or classes is required, the affirmative vote of the majority of shares of such class or classes present in person or represented by proxy at the meeting) shall decide any matter (other than the election of Directors) brought before such meeting, unless the matter is one upon which by express provision of law, the certificate of incorporation or these By-Laws, a different vote is required, in which case such express provision shall govern and control the decision of such matter. The stock of holders who abstain from voting on any matter shall be deemed not to have been voted on such matter. Directors shall be elected by a plurality of the votes of the shares present in person or by remote communication, or represented by proxy at the meeting, entitled to vote and voting on the election of Directors.

Section 9. Voting and Proxies. Unless otherwise provided in the certificate of incorporation, each stockholder shall at every meeting of the stockholders be entitled to one vote for each share of capital stock having voting power held of record by such stockholder. Each stockholder entitled to vote at a meeting of stockholders, or to express consent or dissent to corporate action in writing without a meeting, may authorize another person or persons to act for him by proxy, but no such proxy shall be voted or acted upon after three years from its date, unless the proxy provides for a longer period.

Section 10. Action Without Meeting. Any action required to be taken at any annual or special meeting of stockholders, or any action which may be taken at any annual or special meeting of such stockholders, may be taken without a meeting, without prior notice and without a vote, if a consent or consents in writing, setting forth the action so taken, shall be signed and dated by the holders of outstanding stock having not less than the minimum number of votes that would be necessary to authorize or take such action at a meeting at which all shares entitled to vote thereon were present and voted. Prompt notice of the taking of the corporate action without a meeting by less than unanimous written consent shall be given to those stockholders who have not consented in writing. A telegram, cablegram or other electronic transmission consenting to an action to be taken and transmitted by a stockholder or proxyholder, or by a person or persons authorized to act for a stockholder or proxyholder, shall be deemed to be written, signed and dated for the purposes herein, provided that any such telegram, cablegram or other electronic transmission sets forth or is delivered with information from which the Corporation can determine (A) that the telegram, cablegram or other electronic transmission was transmitted by the stockholder or proxyholder or by a person or persons authorized to act for the stockholder or proxyholder and (B) the date on which such stockholder or proxyholder or authorized person or persons transmitted such telegram, cablegram or other electronic transmission. The date on which such telegram, cablegram or electronic transmission is transmitted shall be deemed to be

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the date on which such consent was signed. No consent given by telegram, cablegram or electronic transmission shall be deemed to have been delivered until such consent is reproduced in paper form and until such paper form shall be delivered in accordance with Section 228 of the General Corporation Law of Delaware, to the Corporation by delivery to its registered office in Delaware, its principal place of business or an officer or agent of the corporation having custody of the book in which proceedings of meetings of stockholders are recorded. Any copy, facsimile or other reliable reproduction of a consent in writing may be substituted or used in lieu of the original writing for any and all such purposes for which the original writing could be used, provided that such copy, facsimile or other reproduction shall be a complete reproduction of the entire original writing.

ARTICLE II

DIRECTORS

Section 1. Number, Election, Tenure and Qualification. The number of Directors which shall constitute the whole board shall be not less than one. Within such limit, the number of Directors shall be determined by resolution of the Board of Directors or by the stockholders at the annual meeting or at any special meeting of stockholders. The directors shall be elected at the annual meeting or at any special meeting of stockholders, or by written consent in lieu of an annual or special meeting of the stockholders (provided, however, that if such consent is less than unanimous, such action by written consent may be in lieu of holding an annual meeting only if all of the directorships to which directors could be elected at an annual meeting held at the effective time of such action are vacant and are filled by such action), except as provided in section 3 of this Article, and each director elected shall hold office until his successor is elected and qualified, unless sooner displaced. Directors need not be stockholders.

Section 2. Enlargement. The number of the Board of Directors may be increased at any time by vote of a majority of the Directors then in office.

Section 3. Vacancies. Vacancies and newly created Directorships resulting from any increase in the authorized number of Directors may be filled by a majority of the Directors then in office, though less than a quorum, or by a sole remaining director, and the Directors so chosen shall hold office until the next annual election and until their successors are duly elected and shall qualify, unless sooner displaced. If there are no Directors in office, then an election of Directors may be held in the manner provided by statute. In the event of a vacancy in the Board of Directors, the remaining Directors, except as otherwise provided by law or these By-Laws, may exercise the powers of the full board until the vacancy is filled.

Section 4. Resignation and Removal. Any director may resign at any time upon notice given in writing or by electronic transmission to the Corporation at its principal place of business or to the Chief Executive Officer or Secretary. Such resignation shall be effective upon receipt unless it is specified to be effective at some other time or upon the happening of some other event. Any director or the entire Board of Directors may be removed, with or without cause, by the holders of a majority of the shares then entitled to vote at an election of Directors, unless otherwise specified by law or the certificate of incorporation.

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Section 5. General Powers. The business and affairs of the Corporation shall be managed by its Board of Directors, which may exercise all powers of the Corporation and do all such lawful acts and things as are not by statute or by the certificate of incorporation or by these By-Laws directed or required to be exercised or done by the stockholders.

Section 6. Chairman of the Board. If the Board of Directors appoints a chairman of the board, he shall, when present, preside at all meetings of the stockholders and the Board of Directors. He shall perform such duties and possess such powers as are customarily vested in the office of the chairman of the board or as may be vested in him by the Board of Directors.

Section 7. Place of Meetings. The Board of Directors may hold meetings, both regular and special, either within or without the State of Delaware.

Section 8. Regular Meetings. Regular meetings of the Board of Directors may be held without notice at such time and at such place as shall from time to time be determined by the board; provided that any director who is absent when such a determination is made shall be given prompt notice of such determination. A regular meeting of the Board of Directors may be held without notice immediately after and at the same place as the annual meeting of stockholders.

Section 9. Special Meetings. Special meetings of the board may be called by the Chief Executive Officer, Secretary, or on the written request of two (2) or more Directors, or by one director in the event that there is only one director in office. Two (2) days’ notice to each director, either personally or by telegram, cable, telecopy, electronic mail, commercial delivery service, telex or similar means sent to his business or home address, or three (3) days’ notice by written notice deposited in the mail, shall be given to each director by the Secretary or by the officer or one of the Directors calling the meeting. A notice or waiver of notice of a meeting of the Board of Directors need not specify the purposes of the meeting.

Section 10. Quorum, Action at Meeting, Adjournments. At all meetings of the board a majority of Directors then in office, but in no event less than one third of the entire board, shall constitute a quorum for the transaction of business and the act of a majority of the Directors present at any meeting at which there is a quorum shall be the act of the Board of Directors, except as may be otherwise specifically provided by law or by the certificate of incorporation. For purposes of this section, the term “entire board” shall mean the number of Directors last fixed by the stockholders or Directors, as the case may be, in accordance with law and these By- Laws; provided, however, that if less than all the number so fixed of Directors were elected, the “entire board” shall mean the greatest number of Directors so elected to hold office at any one time pursuant to such authorization. If a quorum shall not be present at any meeting of the Board of Directors, a majority of the Directors present thereat may adjourn the meeting from time to time, without notice other than announcement at the meeting, until a quorum shall be present.

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Section 11. Action by Consent. Unless otherwise restricted by the certificate of incorporation or these By-Laws, any action required or permitted to be taken at any meeting of the Board of Directors or of any committee thereof may be taken without a meeting, if all members of the board or committee, as the case may be, consent thereto in writing or electronic transmission, and the writing or writings or electronic transmission or transmissions are filed with the minutes of proceedings of the board or committee. Such filing shall be in paper form if the minutes are maintained in paper form and shall be in electronic form if the minutes are maintained in electronic form.

Section 12. Telephonic Meetings. Unless otherwise restricted by the certificate of incorporation or these By-Laws, members of the Board of Directors or of any committee thereof may participate in a meeting of the Board of Directors or of any committee, as the case may be, by means of conference telephone or similar communications equipment by means of which all persons participating in the meeting can hear each other, and such participation in a meeting shall constitute presence in person at the meeting.

Section 13. Committees. The Board of Directors may designate one or more committees, each committee to consist of one or more of the Directors of the Corporation. The board may designate one or more Directors as alternate members of any committee, who may replace any absent or disqualified member at any meeting of the committee. Any such committee, to the extent provided in the resolution of the Board of Directors, shall have and may exercise all the powers and authority of the Board of Directors in the management of the business and affairs of the Corporation, and may authorize the seal of the Corporation to be affixed to all papers which may require it; but no such committee shall have the power or authority in reference to (a) adopting, amending or repealing the By-Laws of the Corporation or any of them or (b) approving or adopting, or recommending to the stockholders any action or matter expressly required by law to be submitted to stockholders for approval. Such committee or committees shall have such name or names as may be determined from time to time by resolution adopted by the Board of Directors. Each committee shall keep regular minutes of its meetings and make such reports to the Board of Directors as the Board of Directors may request. Except as the Board of Directors may otherwise determine, any committee may make rules for the conduct of its business, but unless otherwise provided by the Directors or in such rules, its business shall be conducted as nearly as possible in the same manner as is provided in these By- Laws for the conduct of its business by the Board of Directors.

Section 14. Compensation. Unless otherwise restricted by the certificate of incorporation or these By-Laws, the Board of Directors shall have the authority to fix from time to time the compensation of Directors. The Directors may be paid their expenses, if any, of attendance at each meeting of the Board of Directors and the performance of their responsibilities as Directors and may be paid a fixed sum for attendance at each meeting of the Board of Directors and/or a stated salary as director. No such payment shall preclude any director from serving the Corporation or its parent or subsidiary corporations in any other capacity and receiving compensation therefor. The Board of Directors may also allow compensation for members of special or standing committees for service on such committees.

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ARTICLE III

OFFICERS

Section 1. Enumeration. The officers of the Corporation shall be chosen by the Board of Directors and shall be a President, a Secretary and a Treasurer and such other officers with such titles, terms of office and duties as the Board of Directors may from time to time determine, including a Chairman of the Board, one or more Vice-Presidents, and one or more Assistant Secretaries and Assistant Treasurers. If authorized by resolution of the Board of Directors, the Chief Executive Officer may be empowered to appoint from time to time Assistant Secretaries and Assistant Treasurers. Any number of offices may be held by the same person, unless the Certificate of Incorporation or these By-Laws otherwise provide.

Section 2. Election. The Board of Directors at its first meeting after each annual meeting of stockholders shall choose a President, a Secretary and a Treasurer. Other officers may be appointed by the Board of Directors at such meeting, at any other meeting, or by written consent.

Section 3. Tenure. The officers of the Corporation shall hold office until their successors are chosen and qualify, unless a different term is specified in the vote choosing or appointing him, or until his earlier death, resignation or removal. Any officer elected or appointed by the Board of Directors or by the Chief Executive Officer may be removed at any time, with or without cause, by the affirmative vote of a majority of the Board of Directors or a committee duly authorized to do so, except that any officer appointed by the Chief Executive Officer may also be removed at any time, with or without cause, by the Chief Executive Officer. Any vacancy occurring in any office of the Corporation may be filled by the Board of Directors, at its discretion. Any officer may resign by delivering his written resignation to the Corporation at its principal place of business or to the Chief Executive Officer or the Secretary. Such resignation shall be effective upon receipt unless it is specified to be effective at some other time or upon the happening of some other event.

Section 4. President. The President shall be the Chief Operating Officer of the Corporation. He shall also be the Chief Executive Officer unless the Board of Directors otherwise provides. If no Chief Executive Officer shall have been appointed by the Board of Directors, all references herein to the “Chief Executive Officer” shall be to the President. The President shall, unless the Board of Directors provides otherwise in a specific instance or generally, preside at all meetings of the stockholders and the Board of Directors, have general and active management of the business of the Corporation and see that all orders and resolutions of the Board of Directors are carried into effect. The President shall execute bonds, mortgages, and other contracts requiring a seal, under the seal of the Corporation, except where required or permitted by law to be otherwise signed and executed and except where the signing and execution thereof shall be expressly delegated by the Board of Directors to some other officer or agent of the Corporation.

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Section 5. Vice-Presidents. In the absence of the President or in the event of his or her inability or refusal to act, the Vice-President, or if there be more than one Vice-President, the Vice-Presidents in the order designated by the Board of Directors or the Chief Executive Officer (or in the absence of any designation, then in the order determined by their tenure in office) shall perform the duties of the President, and when so acting, shall have all the powers of and be subject to all the restrictions upon the President. The Vice-Presidents shall perform such other duties and have such other powers as the Board of Directors or the Chief Executive Officer may from time to time prescribe.

Section 6. Secretary. The Secretary shall have such powers and perform such duties as are incident to the office of Secretary. The Secretary shall maintain a stock ledger and prepare lists of stockholders and their addresses as required and shall be the custodian of corporate records. The Secretary shall attend all meetings of the Board of Directors and all meetings of the stockholders and record all the proceedings of the meetings of the Corporation and of the Board of Directors in a book to be kept for that purpose and shall perform like duties for the standing committees when required. The Secretary shall give, or cause to be given, notice of all meetings of the Stockholders and special meetings of the Board of Directors, and shall perform such other duties as may be from time to time prescribed by the Board of Directors or Chief Executive Officer, under whose supervision the Secretary shall be. The Secretary shall have custody of the corporate seal of the Corporation and the Secretary, or an assistant Secretary, shall have authority to affix the same to any instrument requiring it and when so affixed, it may be attested by his or her signature or by the signature of such assistant Secretary. The Board of Directors may give general authority to any other officer to affix the seal of the Corporation and to attest the affixing by his or her signature.

Section 7. Assistant Secretaries. The assistant Secretary, or if there be more than one, the assistant secretaries in the order determined by the Board of Directors, the Chief Executive Officer or the Secretary (or if there be no such determination, then in the order determined by their tenure in office), shall, in the absence of the Secretary or in the event of his or her inability or refusal to act, perform the duties and exercise the powers of the Secretary and shall perform such other duties and have such other powers as the Board of Directors, the Chief Executive Officer or the Secretary may from time to time prescribe. In the absence of the Secretary or any assistant Secretary at any meeting of stockholders or Directors, the person presiding at the meeting shall designate a temporary or acting Secretary to keep a record of the meeting.

Section 8. Treasurer. The Treasurer shall perform such duties and shall have such powers as may be assigned to him or her by the Board of Directors or the Chief Executive Officer. In addition, the Treasurer shall perform such duties and have such powers as are incident to the office of Treasurer. The Treasurer shall have the custody of the corporate funds and securities and shall keep full and accurate accounts of receipts and disbursements in books belonging to the Corporation and shall deposit all moneys and other valuable effects in the name and to the credit of the Corporation in such depositories as may be designated by the Board of Directors. He shall disburse the funds of the Corporation as may be ordered by the Board of Directors, taking proper vouchers for such disbursements, and shall render to the Chief Executive Officer and the Board of Directors, when the Chief Executive Officer or Board of Directors so requires, an account of all his or her transactions as Treasurer and of the financial condition of the Corporation.

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Section 9. Assistant Treasurers. The assistant Treasurer, or if there shall be more than one, the assistant Treasurers in the order determined by the Board of Directors, the Chief Executive Officer or the Treasurer (or if there be no such determination, then in the order determined by their tenure in office), shall, in the absence of the Treasurer or in the event of his or her inability or refusal to act, perform the duties and exercise the powers of the Treasurer and shall perform such other duties and have such other powers as the Board of Directors, the Chief Executive Officer or the Treasurer may from time to time prescribe.

Section 10. Bond. If required by the Board of Directors, any officer shall give the Corporation a bond in such sum and with such surety or sureties and upon such terms and conditions as shall be satisfactory to the Board of Directors, including without limitation a bond for the faithful performance of the duties of his office and for the restoration to the Corporation of all books, papers, vouchers, money and other property of whatever kind in his possession or under his control and belonging to the Corporation.

ARTICLE IV

NOTICES

Section 1. Delivery. Whenever, under the provisions of law, or of the Certificate of Incorporation or these By-Laws, notice is required to be given to any person, such notice may be given by mail, addressed to such person, at his address as it appears on the records of the Corporation, with postage thereon prepaid, and such notice shall be deemed to be given at the time when the same shall be deposited in the United States mail. Unless written notice by mail is required by law, notice may also be given by telegram, cable, telecopy, commercial delivery service, telex or similar means, addressed to such person at his address as it appears on the records of the corporation, in which case such notice shall be deemed to be given when delivered into the control of the persons charged with effecting such transmission, the transmission charge to be paid by the Corporation or the person sending such notice and not by the addressee. Notice may also be given to stockholders by a form of electronic transmission in accordance with and subject to the provisions of Section 232 of the General Corporation Law of Delaware. Oral notice or other in-hand delivery (in person or by telephone) shall be deemed given at the time it is actually given.

Section 2. Waiver of Notice. Whenever any notice is required to be given under the provisions of law or of the certificate of incorporation or of these By-Laws, a waiver thereof in writing, signed by the person or persons entitled to said notice or a waiver by electronic transmission by the person entitled to notice, whether before or after the time stated therein, shall be deemed equivalent thereto.

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ARTICLE V

INDEMNIFICATION

Section 1. Actions other than by or in the Right of the Corporation. The corporation shall indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the right of the Corporation) by reason of the fact that such person is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the Corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, against expenses (including attorneys’ fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by such person in connection with such action, suit or proceeding if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the Corporation, and, with respect to any criminal action or proceedings, had no reasonable cause to believe such person’s conduct was unlawful. The termination of any action, suit or proceeding by judgment, order, settlement, conviction, or upon a plea of nolo contendere or its equivalent, shall not, of itself, create a presumption that the person did not act in good faith and in a manner which such person reasonably believed to be in or not opposed to the best interests of the corporation, and, with respect to any criminal action or proceeding, had reasonable cause to believe that such person’s conduct was unlawful.

Section 2. Actions by or in the Right of the Corporation. The corporation shall indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action or suit by or in the right of the Corporation to procure a judgment in its favor by reason of the fact that he or she is or was a director, officer, employee or agent of the Corporation, or is or was serving at the request of the Corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise

against expenses (including attorneys’ fees) actually and reasonably incurred by such person in connection with the defense or settlement of such action or suit if such person acted in good faith and in a manner he or she reasonably believed to be in or not opposed to the best interests of the Corporation and except that no indemnification shall be made in respect of any claim, issue or matter as to which such person shall have been adjudged to be liable unless and only to the extent that the Court of Chancery of the State of Delaware or the court in which such action or suit was brought shall determine upon application that, despite the adjudication of liability but in view of all the circumstances of the case, such person is fairly and reasonably entitled to indemnity for such expenses which the Court of Chancery of the State of Delaware or such other court shall deem proper.

Section 3. Success on the Merits. To the extent that any person described in Section 1 or 2 of this Article V has been successful on the merits or otherwise in defense of any action, suit or proceeding referred to in said Sections, or in defense of any claim, issue or matter therein, he shall be indemnified against expenses (including attorneys’ fees) actually and reasonably incurred by him in connection therewith.

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Section 4. Specific Authorization. Any indemnification under Section 1 or 2 of this Article V (unless ordered by a court) shall be made by the Corporation only as authorized in the specific case upon a determination that indemnification of any person described in said Sections is proper in the circumstances because he has met the applicable standard of conduct set forth in said Sections. Such determination shall be made (1) by the Board of Directors by a majority vote of Directors who were not parties to such action, suit or proceeding (even though less than a quorum), or (2) if there are no disinterested Directors or if a majority of disinterested Directors so directs, by independent legal counsel (who may be regular legal counsel to the Corporation) in a written opinion, or (3) by the stockholders of the Corporation.

Section 5. Advance Payment. Expenses incurred in defending a pending or threatened civil or criminal action, suit or proceeding may be paid by the Corporation in advance of the final disposition of such action, suit or proceeding upon receipt of an undertaking by or on behalf of any person described in said Section to repay such amount if it shall ultimately be determined that he or she is not entitled to indemnification by the Corporation as authorized in this Article V.

Section 6. Non-Exclusivity. The indemnification and advancement of expenses provided by, or granted pursuant to, the other Sections of this Article V shall not be deemed exclusive of any other rights to which those provided indemnification or advancement of expenses may be entitled under any By-Law, agreement, vote of stockholders or disinterested Directors or otherwise, both as to action in his official capacity and as to action in another capacity while holding such office.

Section 7. Insurance. The Board of Directors may authorize, by a vote of the majority of the full board, the Corporation to purchase and maintain insurance on behalf of any person who is or was a director, officer, employee or agent of the Corporation, or is or was serving at the request of the Corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise against any liability asserted against him and incurred by him in any such capacity, or arising out of his status as such, whether or not the Corporation would have the power to indemnify him against such liability under the provisions of this Article V.

Section 8. Continuation of Indemnification and Advancement of Expenses. The indemnification and advancement of expenses provided by, or granted pursuant to, this Article V shall continue as to a person who has ceased to be a director, officer, employee or agent and shall inure to the benefit of the heirs, executors and administrators of such a person.

Section 9. Severability. If any word, clause or provision of this Article V or any award made hereunder shall for any reason be determined to be invalid, the provisions hereof shall not otherwise be affected thereby but shall remain in full force and effect.

Section 10. Intent of Article. The intent of this Article V is to provide for indemnification and advancement of expenses to the fullest extent permitted by Section 145 of the General Corporation Law of Delaware. To the extent that such Section or any successor section may be amended or supplemented from time to time, this Article V shall be amended automatically and construed so as to permit indemnification and advancement of expenses to the fullest extent from time to time permitted by law.

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ARTICLE VI

CAPITAL STOCK

Section 1. Certificates of Stock. Every holder of stock in the Corporation shall be entitled to have a certificate, signed by, or in the name of the Corporation by, the chairman or Vice-chairman of the Board of Directors, or the President or a Vice-President and the Treasurer or an assistant Treasurer, or the Secretary or an assistant Secretary of the Corporation, certifying the number of shares owned by such holder in the Corporation. Any or all of the signatures on the certificate may be a facsimile. In case any officer, transfer agent or registrar who has signed or whose facsimile signature has been placed upon a certificate shall have ceased to be such officer, transfer agent or registrar before such certificate is issued, it may be issued by the Corporation with the same effect as if he were such officer, transfer agent or registrar at the date of issue. Certificates may be issued for partly paid shares and in such case upon the face or back of the certificates issued to represent any such partly paid shares, the total amount of the consideration to be paid therefor, and the amount paid thereon shall be specified.

Section 2. Lost Certificates. The Board of Directors may direct a new certificate or certificates to be issued in place of any certificate or certificates theretofore issued by the Corporation alleged to have been lost, stolen or destroyed. When authorizing such issue of a new certificate or certificates, the Board of Directors may, in its discretion and as a condition precedent to the issuance thereof, require the owner of such lost, stolen or destroyed certificate or certificates, or his legal representative, to give reasonable evidence of such loss, theft or destruction, to advertise the same in such manner as it shall require and/or to give the Corporation a bond in such sum as it may direct as indemnity against any claim that may be made against the Corporation with respect to the certificate alleged to have been lost, stolen or destroyed or the issuance of such new certificate.

Section 3. Transfer of Stock; Restriction on Transfer. Upon surrender to the Corporation or the transfer agent of the Corporation of a certificate for shares, duly endorsed or accompanied by proper evidence of succession, assignment or authority to transfer, and proper evidence of compliance with other conditions to rightful transfer, it shall be the duty of the Corporation to issue a new certificate to the person entitled thereto, cancel the old certificate and record the transaction upon its books. Notwithstanding the foregoing, the holder of any security of the Corporation (a “Security Holder”) shall not transfer, assign, encumber or otherwise dispose of any security of the Corporation (a “Security”), other than by means of a Permitted Transfer (as defined below), without the consent of a majority of the Directors. If any provision(s) of any agreement(s) currently in effect by and between the Corporation and any Security Holder (the “Security Holder Agreement(s)”) conflicts with this Section 3, this Section shall govern, and the non-conflicting remainder of the Security Holder Agreement(s) shall continue in full force and effect. A “Permitted Transfer” as used in this Section 3 shall be defined as:

(i) any repurchase of a Security by the Corporation: (a) at cost, upon the occurrence of certain events, such as the termination of employment or services; or (b) at any price pursuant to the Corporation’s exercise of a right of first refusal to purchase such shares;

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(ii) any transfer to a Security Holder’s Immediate Family (as defined below) or a trust or similar estate planning vehicle for the benefit of the Security Holder or the Security Holder’s Immediate Family (“Immediate Family” as used herein shall mean any child, stepchild, grandchild or other descendant, any parent, stepparent, grandparent or other ancestor, any spouse, former spouse, sibling, niece, nephew, uncle, aunt, mother-in-law, father-in-law, son-in-law, daughter-in-law, brother-in-law or sister-in-law, including adoptive relationships, or any person deemed to be a Spousal Equivalent (as used herein, a person is deemed to be a “Spousal Equivalent” provided the following circumstances are true: (a) irrespective of whether or not the relevant person and the Spousal Equivalent are the same sex, they are the sole spousal equivalent of the other for the last twelve (12) months, (b) they intend to remain so indefinitely, (c) neither are married to anyone else, (d) both are at least 18 years of age and mentally competent to consent to contract, (e) they are not related by blood to a degree of closeness that would prohibit legal marriage in the state in which they legally reside, and (f) they are jointly responsible for each other’s common welfare and financial obligations));

(iii) as a charitable or donative transfer for no consideration to a federally recognized tax-exempt organization;

(iv) any transfer effected pursuant to the Security Holder’s will or the laws of intestate succession;

(v) if the Security Holder is a partnership, limited liability company, or corporation, any transfer to the partners, members, retired partners, retired members, stockholders, and/or Affiliates (as defined below) of such Security Holder (“Affiliate” as used herein shall mean any person or entity who or which, directly or indirectly, controls, is controlled by, or is under common control with such Security Holder, including without limitation any general partner, managing partner, officer or director of such Security Holder or any venture capital fund now or hereafter existing that is controlled by one or more general partners or managing members of, or shares the same management company with, such Security Holder); and/or

(vi) any transfer approved by the Board of Directors; notwithstanding the foregoing, if a Permitted Transfer is approved pursuant to this Section 3(vi) and the Securities of the transferring party are subject to co-sale rights (the “Co-Sale Rights”), the persons and/or entities entitled to the Co-Sale Rights shall be permitted to exercise their respective Co-Sale Rights in conjunction with this specific Permitted Transfer without any additional approval of the Board of Directors.

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The foregoing restriction on transfer shall lapse upon the earlier of (i) immediately prior to a Liquidation Transaction (as defined below), or (ii) immediately prior to the Corporation’s sale of its common stock in a firm commitment underwritten public offering pursuant to a registration statement under the Securities Act of 1933. A “Liquidation Transaction” as used herein shall mean any event in which the Corporation shall (a) sell, convey, exclusively license or otherwise dispose of all or substantially all of its property, assets or business, (b) merge with or into or consolidate with any other corporation, limited liability company or other entity (other than a wholly-owned subsidiary of the Corporation), (c) close in a transfer (whether by merger, consolidation or otherwise), in one transaction or a series of related transactions to which the Corporation is a party, to a person or group of affiliated persons (other than an underwriter of the Corporation’s securities) if, after such closing, such person or group of affiliated persons would hold 50% or more of the outstanding voting stock of the Corporation (or the surviving or acquired entity) or (d) effect a liquidation, dissolution or winding up of the Corporation; provided that none of the following shall be considered a Liquidation Transaction: (x) a merger effected exclusively for the purpose of changing the domicile of the Corporation, (y) an equity financing in which the Corporation is the surviving corporation, or (z) a transaction in which the stockholders of the Corporation immediately prior to the transaction own 50% or more of the voting power of the surviving corporation following the transaction.

Section 4. Record Date. In order that the Corporation may determine the stockholders entitled to notice of or to vote at any meeting of stockholders or any adjournment thereof, the Board of Directors may fix a record date, which shall not precede the date upon which the resolution fixing the record date is adopted by the Board of Directors, and which shall not be more than sixty days nor less then ten days before the date of such meeting. A determination of stockholders of record entitled to notice of or to vote at a meeting of stockholders shall apply to any adjournment of the meeting; provided, however, that the Board of Directors may fix a new record date for the adjourned meeting. If no record date is fixed, the record date for determining stockholders entitled to notice of or to vote at a meeting of stockholders shall be at the close of business on the day before the day on which notice is given, or, if notice is waived, at the close of business on the day before the day on which the meeting is held. In order that the Corporation may determine the stockholders entitled to consent to corporate action in writing without a meeting, the Board of Directors may fix a record date, which shall not precede the date upon which the resolution fixing the record date is adopted by the Board of Directors, and which shall not be more than ten days after the date upon which the resolution fixing the record date is adopted by the Board of Directors. If no record date is fixed, the record date for determining stockholders entitled to consent to corporate action in writing without a meeting, when no prior action by the Board of Directors is required by statute, shall be the first date on which a signed written consent setting forth the action taken or proposed to be taken is delivered to the Corporation as provided in Section 10 of Article I. If no record date is fixed and prior action by the Board of Directors is required, the record date for determining stockholders entitled to consent to corporate action in writing without a meeting shall be at the close of business on the date on which the Board of Directors adopts the resolution taking such prior action. In order that the Corporation may determine the stockholders entitled to receive payment of any dividend or other distribution or allotment of any rights or the stockholders entitled to exercise any rights in respect of any change, conversion or exchange of stock, or for the purpose of any other lawful action, the Board of Directors may fix a record date, which shall not precede the date upon which the resolution fixing the record date is adopted, and which shall be not more than sixty days prior to such action. If no record date is fixed, the record date for determining stockholders for any such purpose shall be at the close of business on the day on which the Board of Directors adopts the resolution relating to such purpose.

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Section 5. Registered Stockholders. The Corporation shall be entitled to recognize the exclusive right of a person registered on its books as the owner of shares to receive dividends, and to vote as such owner, and to hold liable for calls and assessments a person registered on its books as the owner of shares, and shall not be bound to recognize any equitable or other claim to or interest in such share or shares on the part of any other person, whether or not it shall have express or other notice thereof, except as otherwise provided by the laws of Delaware.

ARTICLE VII

CERTAIN TRANSACTIONS

Section 1. Transactions with Interested Parties. No contract or transaction between the Corporation and one or more of its Directors or officers, or between the Corporation and any other corporation, partnership, association, or other organization in which one or more of its Directors or officers are Directors or officers, or have a financial interest, shall be void or voidable solely for this reason, or solely because the director or officer is present at or participates in the meeting of the board or committee thereof which authorizes the contract or transaction or solely because his or their votes are counted for such purpose, if:

(i) The material facts as to his relationship or interest and as to the contract or transaction are disclosed or are known to the Board of Directors or the committee, and the board or committee in good faith authorizes the contract or transaction by the affirmative votes of a majority of the disinterested Directors, even though the disinterested Directors be less than a quorum; or

(ii) The material facts as to his relationship or interest and as to the contract or transaction are disclosed or are known to the stockholders entitled to vote thereon, and the contract or transaction is specifically approved in good faith by vote of the stockholders; or

(iii) The contract or transaction is fair as to the Corporation as of the time it is authorized, approved or ratified, by the Board of Directors, a committee thereof, or the stockholders.

Section 2. Quorum. Common or interested Directors may be counted in determining the presence of a quorum at a meeting of the Board of Directors or of a committee which authorizes the contract or transaction.

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ARTICLE VIII

GENERAL PROVISIONS

Section 1. Dividends. Dividends upon the capital stock of the corporation, if any, may be declared by the Board of Directors at any regular or special meeting or by written con- sent, pursuant to law. Dividends may be paid in cash, in property, or in shares of the capital stock, subject to the provisions of the certificate of incorporation.

Section 2. Reserves. The Directors may set apart out of any funds of the Corporation available for dividends a reserve or reserves for any proper purpose and may abolish any such reserve.

Section 3. Checks. All checks or demands for money and notes of the Corporation shall be signed by such officer or officers or such other person or persons as the Board of Directors may from time to time designate.

Section 4. Fiscal Year. The fiscal year of the Corporation shall be fixed by resolution of the Board of Directors.

Section 5. Seal. The Board of Directors may, by resolution, adopt a corporate seal. The corporate seal shall have inscribed thereon the name of the Corporation, the year of its organization and the word “Delaware.” The seal may be used by causing it or a facsimile thereof to be impressed or affixed or reproduced or otherwise. The seal may be altered from time to time by the Board of Directors.

ARTICLE IX

AMENDMENTS

These By-Laws may be altered, amended or repealed or new By-Laws may be adopted by the stockholders or by the Board of Directors, when such power is conferred upon the Board of Directors by the certificate of incorporation, at any regular meeting of the stockholders or of the Board of Directors or at any special meeting of the stockholders or of the Board of Directors provided, however, that in the case of a regular or special meeting of stockholders, notice of such alteration, amendment, repeal or adoption of new By-Laws be contained in the notice of such meeting.

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Register of Amendments to the By-Laws

Date	Section Affected	Change
February 5, 2021	Article VI, Section 3(v)	Subsection (v) of Section 3, Article VI of the Bylaws shall be deleted in its entirety and replaced with the following:
		“(v) if the Security Holder is a partnership, limited liability company, or corporation, any transfer to the partners, members, retired partners, retired members, stockholders, and/or Affiliates (as defined in this section) of such Security Holder (“Affiliate” or “Affiliates” as used herein means, with respect to any specified Security Holder, any other person or entity who directly or indirectly, controls, is controlled by or is under common control with such Security Holder, including without limitation any general partner, managing member, investment advisor, officer or director of such Security Holder, or any venture capital fund, other investment fund or registered investment company now or hereafter existing which is controlled by one or more general partners, investment advisors or managing members of, or shares the same management company or investment advisor with, such Security Holder); and/or”

AMENDMENT NO. 1 TO THE

AMENDED AND RESTATED BYLAWS

OF

CYTEIR THERAPEUTICS, INC.

APPROVED BY BOARD: FEBRUARY 5, 2021

APPROVED BY STOCKHOLDERS: FEBRUARY 5, 2021

The Amended and Restated Bylaws (the “Bylaws”) of CYTEIR THERAPEUTICS, INC. (the “Company”) are hereby amended as follows:

1. Subsection (v) of Section 3, Article VI of the Bylaws shall be deleted in its entirety and replaced with the following:

“(v) if the Security Holder is a partnership, limited liability company, or corporation, any transfer to the partners, members, retired partners, retired members, stockholders, and/or Affiliates (as defined in this section) of such Security Holder (“Affiliate” or “Affiliates” as used herein means, with respect to any specified Security Holder, any other person or entity who directly or indirectly, controls, is controlled by or is under common control with such Security Holder, including without limitation any general partner, managing member, investment advisor, officer or director of such Security Holder, or any venture capital fund, other investment fund or registered investment company now or hereafter existing which is controlled by one or more general partners, investment advisors or managing members of, or shares the same management company or investment advisor with, such Security Holder); and/or”

[Signature page follows]

I, the undersigned, certify that I am the duly elected and acting President and Chief Executive Officer of the Company, and that the above amendment to the Bylaws was duly adopted by the Company’s Board of Directors and stockholders on the dates set forth above.

By:	/s/ Markus Renschler
Name:	Markus Renschler
Title:	President & Chief Executive Officer

[Signature Page to Amendment I to the Bylaws]

EX-4.2

Exhibit 4.2

Execution Version

CYTEIR THERAPEUTICS, INC.

SECOND AMENDED AND RESTATED

INVESTORS’ RIGHTS AGREEMENT

FEBRUARY 5, 2021

TABLE OF CONTENTS

		Page
1.  Definitions			1
1.1	“Affiliate”		1
1.2	“Common Stock”		2
1.3	“Damages”		2
1.4	“Default Conversion Shares”		2
1.5	“Derivative Securities”		2
1.6	“Exchange Act”		2
1.7	“Excluded Registration”		2
1.8	“Form S-1”		2
1.9	“Form S-3”		2
1.10	“GAAP”		2
1.11	“Holder”		2
1.12	“Immediate Family Member”		3
1.13	“Initiating Holders”		3
1.14	“IPO”		3
1.15	“Major Investor”		3
1.16	“New Securities”		3
1.17	“Person”		3
1.18	“Preferred Director”		3
1.19	“Preferred Stock”		3
1.20	“RA Capital Fund” means		3
1.21	“Registrable Securities”		3
1.22	“Registrable Securities then outstanding”		3
1.23	“Requisite Directors”		4
1.24	“Restated Certificate”		4
1.25	“Restricted Securities”		4
1.26	“SEC”		4
1.27	“SEC Rule 144”		4
1.28	“SEC Rule 145”		4
1.29	“Securities Act”		4
1.30	“Selling Expenses”		4

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1.31	“Series A Preferred Stock”	4
1.32	“Series B Preferred Stock”	4
1.33	“Series C Preferred Stock”	4
2.  Registration Rights		4
2.1	Demand Registration	4
2.2	Company Registration	6
2.3	Underwriting Requirements	6
2.4	Obligations of the Company	8
2.5	Furnish Information	9
2.6	Expenses of Registration	9
2.7	Delay of Registration	10
2.8	Indemnification	10
2.9	Reports Under Exchange Act	12
2.10	Limitations on Subsequent Registration Rights	13
2.11	“Market Stand-off” Agreement	13
2.12	Restrictions on Transfer	14
2.13	Termination of Registration Rights	15
3.  Management and Information Rights		15
3.1	Delivery of Financial Statements	15
3.2	Inspection	17
3.3	Termination of Information	17
3.4	Confidentiality	17
3.5	Critical Technology Matters	18
4.  Rights to Future Stock Issuances		18
4.1	Right of First Offer	18
4.2	Termination	20
4.3	Special Mandatory Conversion	20
5.  Additional Covenants		20
5.1	Insurance	20
5.2	Employee Agreements	20
5.3	Employee Stock	20
5.4	Qualified Small Business Stock	21
5.5	Matters Requiring Investor Director Approval	21
5.6	Board Matters	22

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5.7	Successor Indemnification	22
5.8	Indemnification Matters	23
5.9	Termination of Covenants	23
5.10	Right to Conduct Activities	23
5.11	Restrictions on Publicity	24
5.12	Expenses of Counsel.	24
5.13	Anti-Harassment Policy	25
5.14	Real Property Holding Corporation	25
6. Miscellaneous		25
6.1	Successors and Assigns	25
6.2	Governing Law	26
6.3	Counterparts	26
6.4	Titles and Subtitles	26
6.5	Notices	26
6.6	Amendments and Waivers	27
6.7	Severability	27
6.8	Aggregation of Stock	27
6.9	Additional Investors	27
6.10	Entire Agreement	28
6.11	Dispute Resolution	28
6.12	Delays or Omissions	28
6.13	Acknowledgment	29
6.14	Default	29
6.15	Limitation of Liability; Freedom to Operate Affiliates	29
6.16	Further Assurances	29

Schedule A – Schedule of Investors

Schedule B – Schedule of Key Investors

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SECOND AMENDED AND RESTATED

INVESTORS’ RIGHTS AGREEMENT

This Second Amended and Restated Investors’ Rights Agreement (the “Agreement”) is made as of February 5, 2021, by and among Cyteir Therapeutics, Inc., a Delaware corporation (the “Company”) and each of the individuals and entities listed on Schedule A (together with any subsequent investors, or transferees, who become parties hereto pursuant to Subsection 6.9 below, the “Investors”).

RECITALS

WHEREAS, certain of the Investors (the “Existing Investors”) hold shares of the Company’s Preferred Stock and/or shares of Common Stock issued upon conversion thereof, and possess registration rights, information rights, rights of first offer, and other rights pursuant to an Amended and Restated Investors’ Rights Agreement dated as of September 27, 2019, between the Company and such Investors (the “Prior Agreement”);

WHEREAS, the Existing Investors are holders of a majority of the Registrable Securities of the Company (as defined in the Prior Agreement), and desire to amend and restate the Prior Agreement in its entirety and to accept the rights created pursuant to this Agreement in lieu of the rights granted to them under the Prior Agreement; and

WHEREAS, certain of the Investors are parties to that certain Series C Preferred Stock Purchase Agreement of even date herewith between the Company and certain of the Investors (the “Purchase Agreement”), under which certain of the Company’s and such Investors’ obligations are conditioned upon the execution and delivery of this Agreement by such Existing Investors holding at least a majority of the Registrable Securities, and the Company;

NOW, THEREFORE, the Company and the Investors, including the Existing Investors, each hereby agree that the Prior Agreement shall be amended and restated, and the parties to this Agreement further agree as follows:

1. Definitions. For purposes of this Agreement:

1.1 “Affiliate” means, with respect to any specified Person, any other Person who, directly or indirectly, controls, is controlled by, or is under common control with such Person, including, without limitation, any general partner, managing member, investment adviser, officer or, director or trustee of such Person, or any venture capital fund, other investment fund or registered investment company now or hereafter existing that is controlled by one or more general partners, managing members or investment advisers of, or shares the same management company or investment adviser with, such Person. Notwithstanding the foregoing, where the term “Person” refers to Novo Holdings A/S, in lieu of the foregoing definition, the term “Affiliate” shall mean Novo Ventures (US) Inc., Novo Holdings Equity US Inc., Novo Holdings Equity Asia Pte. Ltd. (together with Novo Holdings A/S, “Novo”), any partner, executive officer or director of Novo or any venture capital fund or other Person now or hereafter existing formed for the purpose of making investments in other Persons that is controlled by or under common control with Novo, and for the avoidance of doubt, shall not include any other affiliate of Novo.

1.2 “Common Stock” means shares of the Company’s common stock, par value $0.001 per share.

1.3 “Damages” means any loss, damage, claim or liability (joint or several) to which a party hereto may become subject under the Securities Act, the Exchange Act, or other federal or state law, insofar as such loss, damage, claim or liability (or any action in respect thereof) arises out of or is based upon (i) any untrue statement or alleged untrue statement of a material fact contained in any registration statement of the Company, including any preliminary prospectus or final prospectus contained therein or any amendments or supplements thereto; (ii) an omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading; or (iii) any violation or alleged violation by the indemnifying party (or any of its agents or Affiliates) of the Securities Act, the Exchange Act, any state securities law, or any rule or regulation promulgated under the Securities Act, the Exchange Act, or any state securities law.

1.4 “Default Conversion Shares” has the meaning ascribed to such term in the Restated Certificate.

1.5 “Derivative Securities” means any securities or rights convertible into, or exercisable or exchangeable for (in each case, directly or indirectly), Common Stock, including options and warrants.

1.6 “Exchange Act” means the Securities Exchange Act of 1934, as amended, and the rules and regulations promulgated thereunder.

1.7 “Excluded Registration” means (i) a registration relating-to the sale of securities to employees of the Company or a subsidiary pursuant to a stock option, stock purchase, or similar plan; (ii) a registration relating to an SEC Rule 145 transaction; (iii) a registration on any form that does not include substantially the same information as would be required to be included in a registration statement covering the sale of the Registrable Securities; or (iv) a registration in which the only Common Stock being registered is Common Stock issuable upon conversion of debt securities that are also being registered.

1.8 “Form S-1” means such form under the Securities Act as in effect on the date hereof or any successor registration form under the Securities Act subsequently adopted by the SEC.

1.9 “Form S-3” means such form under the Securities Act as in effect on the date hereof or any registration form under the Securities Act subsequently adopted by the SEC that permits incorporation of substantial information by reference to other documents filed by the Company with the SEC.

1.10 “GAAP” means generally accepted accounting principles in the United States.

1.11 “Holder” means any holder of Registrable Securities who is a party to this Agreement.

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1.12 “Immediate Family Member” means a child, stepchild, grandchild, parent, stepparent, grandparent, spouse, sibling, mother-in-law, father-in-law, son-in-law, daughter-in-law, brother-in-law, or sister-in-law, including adoptive relationships, of a natural person referred to herein.

1.13 “Initiating Holders” means, collectively, Holders who properly initiate a registration request under this Agreement.

1.14 “IPO” means the Company’s first underwritten public offering of its Common Stock under the Securities Act.

1.15 “Major Investor” means (i) any Investor that, individually or together with such Investor’s Affiliates, holds at least 1,000,000 shares of Registrable Securities (as adjusted for any stock split, stock dividend, combination, or other recapitalization or reclassification effected after the date hereof) and (ii) each RA Capital Fund for so long as such RA Capital Fund holds all of the shares of Series C Preferred Stock purchased by it pursuant to the Purchase Agreement.

1.16 “New Securities” means, collectively, equity securities of the Company, whether or not currently authorized, as well as rights, options, or warrants to purchase such equity securities, or securities of any type whatsoever that are, or may become, convertible or exchangeable into or exercisable for such equity securities.

1.17 “Person” means any individual, corporation, partnership, trust, limited liability company, association or other entity.

1.18 “Preferred Director” means any director of the Company that the holders of record of the Preferred Stock are entitled to elect pursuant to the Restated Certificate.

1.19 “Preferred Stock” means shares of the Company’s Series A Preferred Stock, Series B Preferred Stock and Series C Preferred Stock.

1.20 “RA Capital Fund” means RA Capital Healthcare Fund, L.P. and RA Capital Nexus Fund II, L.P.

1.21 “Registrable Securities” means (i) the Common Stock issuable or issued upon conversion of the Preferred Stock that are not Default Conversion Shares; (ii) any Common Stock, or any Common Stock issued or issuable (directly or indirectly) upon conversion and/or exercise of any other securities of the Company, acquired by the Investors after the date hereof that are not Default Conversion Shares; (iii) any Common Stock issued as (or issuable upon the conversion or exercise of any warrant, right, or other security that is issued as) a dividend or other distribution with respect to, or in exchange for or in replacement of, the shares referenced in clauses (i) and (ii) above; excluding in all cases, however, any Registrable Securities sold by a Person in a transaction in which the applicable rights under this Agreement are not assigned pursuant to Subsection 6.1, and excluding for purposes of Section 2 any shares for which registration rights have terminated pursuant to Subsection 2.13 of this Agreement.

1.22 “Registrable Securities then outstanding” means the number of shares determined by adding the number of shares of outstanding Common Stock that are Registrable Securities and the number of shares of Common Stock issuable (directly or indirectly) pursuant to then exercisable and/or convertible securities that are Registrable Securities.

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1.23 “Requisite Directors” means a majority of the Preferred Directors, provided that if the number of Preferred Directors then in office is two or less, then only the vote of one of the Preferred Directors shall be required.

1.24 “Restated Certificate” means the Company’s Fifth Amended and Restated Certificate of Incorporation, as amended and in effect from time to time.

1.25 “Restricted Securities” means the securities of the Company required to bear the legend set forth in Subsection 2.12(b) hereof.

1.26 “SEC” means the Securities and Exchange Commission.

1.27 “SEC Rule 144” means Rule 144 promulgated by the SEC under the Securities Act.

1.28 “SEC Rule 145” means Rule 145 promulgated by the SEC under the Securities Act.

1.29 “Securities Act” means the Securities Act of 1933, as amended, and the rules and regulations promulgated thereunder.

1.30 “Selling Expenses” means all underwriting discounts, selling commissions, and stock transfer taxes applicable to the sale of Registrable Securities, and fees and disbursements of counsel for any Holder, except for the fees and disbursements of the Selling Holder Counsel borne and paid by the Company as provided in Subsection 2.6.

1.31 “Series A Preferred Stock” means shares of the Company’s Series A Preferred Stock, par value $0.001 per share.

1.32 “Series B Preferred Stock” means shares of the Company’s Series B Preferred Stock, par value $0.001 per share.

1.33 “Series C Preferred Stock” means shares of the Company’s Series C Preferred Stock, par value $0.001 per share.

2. Registration Rights. The Company covenants and agrees as follows:

2.1 Demand Registration.

(a) Form S-1 Demand. If at any time after the earlier of (i) three (3) years after the date of this Agreement or (ii) one hundred eighty (180) days after the effective date of the registration statement for the IPO, the Company receives a request from Holders of a majority of the Registrable Securities then outstanding that the Company file a Form S-1 registration statement with respect to at least forty percent (40%) of the Registrable Securities then outstanding or a lesser percent if the anticipated aggregate offering price, net of Selling Expenses,

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would exceed $15 million, then the Company shall (x) within ten (10) days after the date such request is given, give notice thereof (the “Demand Notice”) to all Holders other than the Initiating Holders; and (y) as soon as practicable, and in any event within sixty (60) days after the date such request is given by the Initiating Holders, file a Form S-1 registration statement under the Securities Act covering all Registrable Securities that the Initiating Holders requested to be registered and any additional Registrable Securities requested to be included in such registration by any other Holders, as specified by notice given by each such Holder to the Company within twenty (20) days of the date the Demand Notice is given, and in each case, subject to the limitations of Subsection 2.1(c) and Subsection 2.3.

(b) Form S-3 Demand. If at any time when it is eligible to use a Form S-3 registration statement, the Company receives a request from Holders of at least thirty percent (30%) of the Registrable Securities then outstanding that the Company file a Form S-3 registration statement with respect to outstanding Registrable Securities of such Holders having an anticipated aggregate offering price, net of Selling Expenses, of at least $2 million, then the Company shall (i) within ten (10) days after the date such request is given, give a Demand Notice to all Holders other than the Initiating Holders; and (ii) as soon as practicable, and in any event within forty-five (45) days after the date such request is given by the Initiating Holders, file a Form S-3 registration statement under the Securities Act covering all Registrable Securities requested to be included in such registration by any other Holders, as specified by notice given by each such Holder to the Company within twenty (20) days of the date the Demand Notice is given, and in each case, subject to the limitations of Subsection 2.1(c) and Subsection 2.3.

(c) Notwithstanding the foregoing obligations, if the Company furnishes to Holders requesting a registration pursuant to this Subsection 2.1 a certificate signed by the Company’s chief executive officer stating that in the good faith judgment of the Company’s Board of Directors it would be materially detrimental to the Company and its stockholders for such registration statement to either become effective or remain effective for as long as such registration statement otherwise would be required to remain effective, because such action would (i) materially interfere with a significant acquisition, corporate reorganization, or other similar transaction involving the Company; (ii) require premature disclosure of material information that the Company has a bona fide business purpose for preserving as confidential; or (iii) render the Company unable to comply with requirements under the Securities Act or Exchange Act, then the Company shall have the right to defer taking action with respect to such filing, and any time periods with respect to filing or effectiveness thereof shall be tolled correspondingly, for a period of not more than one hundred twenty (120) days after the request of the Initiating Holders is given; provided, however, that the Company may not invoke this right more than once in any twelve (12) month period; and provided further that the Company shall not register any securities for its own account or that of any other stockholder during such one hundred twenty (120) day period other than an Excluded Registration.

(d) The Company shall not be obligated to effect, or to take any action to effect, any registration pursuant to Subsection 2.1(a) (i) during the period that is sixty (60) days before the Company’s good faith estimate of the date of filing of, and ending on a date that is one hundred eighty (180) days after the effective date of, a Company-initiated registration, provided, that the Company is actively employing in good faith commercially reasonable efforts to cause such registration statement to become effective; (ii) after the Company has effected three

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registrations pursuant to Subsection 2.1(a); or (iii) if the Initiating Holders propose to dispose of shares of Registrable Securities that may be immediately registered on Form S-3 pursuant to a request made pursuant to Subsection 2.1(b). The Company shall not be obligated to effect, or to take any action to effect, any registration pursuant to Subsection 2.1(b) (i) during the period that is thirty (30) days before the Company’s good faith estimate of the date of filing of, and ending on a date that is ninety (90) days after the effective date of, a Company-initiated registration, provided, that the Company is actively employing in good faith commercially reasonable efforts to cause such registration statement to become effective; or (ii) if the Company has effected two registrations pursuant to Subsection 2.1(b) within the twelve (12) month period immediately preceding the date of such request. A registration shall not be counted as “effected” for purposes of this Subsection 2.1(d) until such time as the applicable registration statement has been declared effective by the SEC, unless the Initiating Holders withdraw their request for such registration, elect not to pay the registration expenses therefor, and forfeit their right to one demand registration statement pursuant to Subsection 2.6, in which case such withdrawn registration statement shall be counted as “effected” for purposes of this Subsection 2.1(d), provided, that if the Initiating Holders withdraw their request for such registration as a result of a material adverse change to the Company, such withdrawn registration statement shall not be counted as “effected” for purposes of this Subsection 2.1(d).

2.2 Company Registration. If the Company proposes to register (including, for this purpose, a registration effected by the Company for stockholders other than the Holders) any of its Common Stock under the Securities Act in connection with the public offering of such securities solely for cash (other than in an Excluded Registration), the Company shall, at such time, promptly give each Holder notice of such registration. Upon the request of each Holder given within twenty (20) days after such notice is given by the Company, the Company shall, subject to the provisions of Subsection 2.3, cause to be registered all of the Registrable Securities that each such Holder has requested to be included in such registration. The Company shall have the right to terminate or withdraw any registration initiated by it under this Subsection 2.2 before the effective date of such registration, whether or not any Holder has elected to include Registrable Securities in such registration. The expenses (other than Selling Expenses) of such withdrawn registration shall be borne by the Company in accordance with Subsection 2.6.

2.3 Underwriting Requirements.

(a) If, pursuant to Subsection 2.1, the Initiating Holders intend to distribute the Registrable Securities covered by their request by means of an underwriting, they shall so advise the Company as a part of their request made pursuant to Subsection 2.1, and the Company shall include such information in the Demand Notice. The underwriter(s) will be selected by the Company and shall be reasonably acceptable to a majority in interest of the Initiating Holders. In such event, the right of any Holder to include such Holder’s Registrable Securities in such registration shall be conditioned upon such Holder’s participation in such underwriting and the inclusion of such Holder’s Registrable Securities in the underwriting to the extent provided herein. All Holders proposing to distribute their securities through such underwriting shall (together with the Company as provided in Subsection 2.4(e)) enter into an underwriting agreement in customary form with the underwriter(s) selected for such underwriting. Notwithstanding any other provision of this Subsection 2.3, if the managing underwriter(s) advise(s) the Initiating Holders in writing that marketing factors require a limitation on the number

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of shares to be underwritten, then the Initiating Holders shall so advise all Holders of Registrable Securities that otherwise would be underwritten pursuant hereto, and the number of Registrable Securities that may be included in the underwriting shall be allocated among such Holders of Registrable Securities, including the Initiating Holders, in proportion (as nearly as practicable) to the number of Registrable Securities owned by each Holder or in such other proportion as shall mutually be agreed to by all such selling Holders; provided, however, that the number of Registrable Securities held by the Holders to be included in such underwriting shall not be reduced unless all other securities are first entirely excluded from the underwriting. To facilitate the allocation of shares in accordance with the above provisions, the Company or the underwriters may round the number of shares allocated to any Holder to the nearest 100 shares.

(b) In connection with any offering involving an underwriting of shares of the Company’s capital stock pursuant to Subsection 2.2, the Company shall not be required to include any of the Holders’ Registrable Securities in such underwriting unless the Holders accept the terms of the underwriting as agreed upon between the Company and its underwriters, and then only in such quantity as the underwriters in their sole discretion determine will not jeopardize the success of the offering by the Company. If the total number of securities, including Registrable Securities, requested by stockholders to be included in such offering exceeds the number of securities to be sold (other than by the Company) that the underwriters in their reasonable discretion determine is compatible with the success of the offering, then the Company shall be required to include in the offering only that number of such securities, including Registrable Securities, which the underwriters and the Company in their sole discretion determine will not jeopardize the success of the offering. If the underwriters determine that less than all of the Registrable Securities requested to be registered can be included in such offering, then the Registrable Securities that are included in such offering shall be allocated among the selling Holders in proportion (as nearly as practicable to) the number of Registrable Securities owned by each selling Holder or in such other proportions as shall mutually be agreed to by all such selling Holders. To facilitate the allocation of shares in accordance with the above provisions, the Company or the underwriters may round the number of shares allocated to any Holder to the nearest 100 shares. Notwithstanding the foregoing, in no event shall (i) the number of Registrable Securities included in the offering be reduced unless all other securities (other than securities to be sold by the Company) are first entirely excluded from the offering, or (ii) the number of Registrable Securities included in the offering be reduced below thirty percent (30%) of the total number of securities included in such offering, unless such offering is the IPO, in which case the selling Holders may be excluded further if the underwriters make the determination described above and no other stockholder’s securities are included in such offering. For purposes of the provision in this Subsection 2.3(b) concerning apportionment, for any selling Holder that is a partnership, limited liability company, or corporation, the partners, members, retired partners, retired members, stockholders, and Affiliates of such Holder, or the estates and Immediate Family Members of any such partners, retired partners, members, and retired members and any trusts for the benefit of any of the foregoing Persons, shall be deemed to be a single “selling Holder,” and any pro rata reduction with respect to such “selling Holder” shall be based upon the aggregate number of Registrable Securities owned by all Persons included in such “selling Holder,” as defined in this sentence.

(c) For purposes of Subsection 2.1, a registration shall not be counted as “effected” if, as a result of an exercise of the underwriter’s cutback provisions in Subsection 2.3(a), fewer than fifty percent (50%) of the total number of Registrable Securities that Holders have requested to be included in such registration statement are actually included.

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2.4 Obligations of the Company. Whenever required under this Section 2 to effect the registration of any Registrable Securities, the Company shall, as expeditiously as reasonably possible:

(a) prepare and file with the SEC a registration statement with respect to such Registrable Securities and use its commercially reasonable efforts to cause such registration statement to become effective and, upon the request of the Holders of a majority of the Registrable Securities registered thereunder, keep such registration statement effective for a period of up to one hundred twenty (120) days or, if earlier, until the distribution contemplated in the registration statement has been completed; provided, however, that (i) such one hundred twenty (120) day period shall be extended for a period of time equal to the period the Holder refrains, at the request of an underwriter of Common Stock (or other securities) of the Company, from selling any securities included in such registration, and (ii) in the case of any registration of Registrable Securities on Form S-3 that are intended to be offered on a continuous or delayed basis, subject to compliance with applicable SEC rules, such one hundred twenty (120) day period shall be extended for up to one hundred fifty (150) days, if necessary, to keep the registration statement effective until all such Registrable Securities are sold;

(b) prepare and file with the SEC such amendments and supplements to such registration statement, and the prospectus used in connection with such registration statement, as may be necessary to comply with the Securities Act in order to enable the disposition of all securities covered by such registration statement;

(c) furnish to the selling Holders such numbers of copies of a prospectus, including a preliminary prospectus, as required by the Securities Act, and such other documents as the Holders may reasonably request in order to facilitate their disposition of their Registrable Securities;

(d) use its commercially reasonable efforts to register and qualify the securities covered by such registration statement under such other securities or blue-sky laws of such jurisdictions as shall be reasonably requested by the selling Holders; provided that the Company shall not be required to qualify to do business or to file a general consent to service of process in any such states or jurisdictions, unless the Company is already subject to service in such jurisdiction and except as may be required by the Securities Act;

(e) in the event of any underwritten public offering, enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the underwriter(s) of such offering;

(f) use its commercially reasonable efforts to cause all such Registrable Securities covered by such registration statement to be listed on a national securities exchange or trading system and each securities exchange and trading system (if any) on which similar securities issued by the Company are then listed;

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(g) provide a transfer agent and registrar for all Registrable Securities registered pursuant to this Agreement and provide a CUSIP number for all such Registrable Securities, in each case not later than the effective date of such registration;

(h) promptly make available for inspection by the selling Holders, any managing underwriter(s) participating in any disposition pursuant to such registration statement, and any attorney or accountant or other agent retained by any such underwriter or selected by the selling Holders, all financial and other records, pertinent corporate documents, and properties of the Company, and cause the Company’s officers, directors, employees, and independent accountants to supply all information reasonably requested by any such seller, underwriter, attorney, accountant, or agent, in each case, as necessary or advisable to verify the accuracy of the information in such registration statement and to conduct appropriate due diligence in connection therewith;

(i) notify each selling Holder, promptly after the Company receives notice thereof, of the time when such registration statement has been declared effective or a supplement to any prospectus forming a part of such registration statement has been filed; and

(j) after such registration statement becomes effective, notify each selling Holder of any request by the SEC that the Company amend or supplement such registration statement or prospectus.

In addition, the Company shall ensure that, at all times after any registration statement covering a public offering of securities of the Company under the Securities Act shall have become effective, its insider trading policy shall provide that the Company’s directors may implement a trading program under Rule 10b5-1 of the Exchange Act.

2.5 Furnish Information. It shall be a condition precedent to the obligations of the Company to take any action pursuant to this Section 2 with respect to the Registrable Securities of any selling Holder that such Holder shall furnish to the Company such information regarding itself, the Registrable Securities held by it, and the intended method of disposition of such securities as is reasonably required to effect the registration of such Holder’s Registrable Securities.

2.6 Expenses of Registration. All expenses (other than Selling Expenses) incurred in connection with registrations, filings, or qualifications pursuant to Section 2, including all registration, filing, and qualification fees; printers’ and accounting fees; fees and disbursements of counsel for the Company; and the reasonable fees and disbursements, not to exceed $25,000, of one counsel for the selling Holders (“Selling Holder Counsel”), shall be borne and paid by the Company; provided, however, that the Company shall not be required to pay for any expenses of any registration proceeding begun pursuant to Subsection 2.1 if the registration request is subsequently withdrawn at the request of the Holders of a majority of the Registrable Securities to be registered (in which case all selling Holders shall bear such expenses pro rata based upon the number of Registrable Securities that were to be included in the withdrawn registration), unless the Holders of a majority of the Registrable Securities agree to forfeit their right to one registration pursuant to Subsection 2.1(a) or Subsection 2.1(b), as the case may be; provided further that if, at the time of such withdrawal, the Holders shall have learned of a material adverse change in the

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condition, business, or prospects of the Company from that known to the Holders at the time of their request and have withdrawn the request with reasonable promptness after learning of such information then the Holders shall not be required to pay any of such expenses and shall not forfeit their right to one registration pursuant to Subsection 2.1(a) or Subsection 2.1(b). All Selling Expenses relating to Registrable Securities registered pursuant to this Section 2 shall be borne and paid by the Holders (other than fees and disbursements of counsel to any Holder, other than the Selling Holder Counsel, which shall be borne solely by the Holder engaging such counsel) pro rata on the basis of the number of Registrable Securities registered on their behalf.

2.7 Delay of Registration. No Holder shall have any right to obtain or seek an injunction restraining or otherwise delaying any registration pursuant to this Agreement as the result of any controversy that might arise with respect to the interpretation or implementation of this Section 2.

2.8 Indemnification. If any Registrable Securities are included in a registration statement under this Section 2:

(a) To the extent permitted by law, the Company will indemnify and hold harmless each selling Holder, and the partners, members, officers, directors, and stockholders of each such Holder; legal counsel and accountants for each such Holder; any underwriter (as defined in the Securities Act) for each such Holder; and each Person, if any, who controls such Holder or underwriter within the meaning of the Securities Act or the Exchange Act, against any Damages, and the Company will pay to each such Holder, underwriter, controlling Person, or other aforementioned Person any legal or other expenses reasonably incurred thereby in connection with investigating or defending any claim or proceeding from which Damages may result, as such expenses are incurred; provided, however, that the indemnity agreement contained in this Subsection 2.8(a) shall not apply to amounts paid in settlement of any such claim or proceeding if such settlement is effected without the consent of the Company, which consent shall not be unreasonably withheld, nor shall the Company be liable for any Damages to the extent that they arise out of or are based upon actions or omissions made in reliance upon and in conformity with written information furnished by or on behalf of any such Holder, underwriter, controlling Person, or other aforementioned Person expressly for use in connection with such registration.

(b) To the extent permitted by law, each selling Holder, severally and not jointly, will indemnify and hold harmless the Company, and each of its directors, each of its officers who has signed the registration statement, each Person (if any), who controls the Company within the meaning of the Securities Act, legal counsel and accountants for the Company, any underwriter (as defined in the Securities Act), any other Holder selling securities in such registration statement, and any controlling Person of any such underwriter or other Holder, against any Damages, in each case only to the extent that such Damages arise out of or are based upon actions or omissions made in reliance upon and in conformity with written information furnished by or on behalf of such selling Holder expressly for use in connection with such registration; and each such selling Holder will pay to the Company and each other aforementioned Person any legal or other expenses reasonably incurred thereby in connection with investigating or defending any claim or proceeding from which Damages may result, as such expenses are incurred; provided, however, that the indemnity agreement contained in this Subsection 2.8(b) shall not apply to amounts paid in settlement of any such claim or proceeding if such settlement is effected without

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the consent of the Holder, which consent shall not be unreasonably withheld; and provided further that in no event shall the aggregate amounts payable by any Holder by way of indemnity or contribution under Subsections 2.8(b) and 2.8(d) exceed the proceeds from the offering received by such Holder (net of any Selling Expenses paid by such Holder), except in the case of fraud or willful misconduct by such Holder.

(c) Promptly after receipt by an indemnified party under this Subsection 2.8 of notice of the commencement of any action (including any governmental action) for which a party may be entitled to indemnification hereunder, such indemnified party will, if a claim in respect thereof is to be made against any indemnifying party under this Subsection 2.8, give the indemnifying party notice of the commencement thereof. The indemnifying party shall have the right to participate in such action and, to the extent the indemnifying party so desires, participate jointly with any other indemnifying party to which notice has been given, and to assume the defense thereof with counsel mutually satisfactory to the parties; provided, however, that an indemnified party (together with all other indemnified parties that may be represented without conflict by one counsel) shall have the right to retain one separate counsel, with the fees and expenses to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented by such counsel in such action. The failure to give notice to the indemnifying party within a reasonable time of the commencement of any such action shall relieve such indemnifying party of any liability to the indemnified party under this Subsection 2.8, to the extent that such failure materially prejudices the indemnifying party’s ability to defend such action. The failure to give notice to the indemnifying party will not relieve it of any liability that it may have to any indemnified party otherwise than under this Subsection 2.8.

(d) To provide for just and equitable contribution to joint liability under the Securities Act in any case in which either (i) any party otherwise entitled to indemnification hereunder makes a claim for indemnification pursuant to this Subsection 2.8 but it is judicially determined (by the entry of a final judgment or decree by a court of competent jurisdiction and the expiration of time to appeal or the denial of the last right of appeal) that such indemnification may not be enforced in such case, notwithstanding the fact that this Subsection 2.8 provides for indemnification in such case, or (ii) contribution under the Securities Act may be required on the part of any party hereto for which indemnification is provided under this Subsection 2.8, then, and in each such case, such parties will contribute to the aggregate losses, claims, damages, liabilities, or expenses to which they may be subject (after contribution from others) in such proportion as is appropriate to reflect the relative fault of each of the indemnifying party and the indemnified party in connection with the statements, omissions, or other actions that resulted in such loss, claim, damage, liability, or expense, as well as to reflect any other relevant equitable considerations. The relative fault of the indemnifying party and of the indemnified party shall be determined by reference to, among other things, whether the untrue or allegedly untrue statement of a material fact, or the omission or alleged omission of a material fact, relates to information supplied by the indemnifying party or by the indemnified party and the parties’ relative intent, knowledge, access to information, and opportunity to correct or prevent such statement or omission; provided, however, that, in any such case, (x) no Holder will be required to contribute any amount in excess of the public offering price of all such Registrable Securities offered and sold by such Holder pursuant to such registration statement, and (y) no Person guilty of fraudulent misrepresentation

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(within the meaning of Section 11(f) of the Securities Act) will be entitled to contribution from any Person who was not guilty of such fraudulent misrepresentation; and provided further that in no event shall a Holder’s liability pursuant to this Subsection 2.8(d), when combined with the amounts paid or payable by such Holder pursuant to Subsection 2.8(b), exceed the proceeds from the offering received by such Holder (net of any Selling Expenses paid by such Holder), except in the case of willful misconduct or fraud by such Holder.

(e) Notwithstanding the foregoing, to the extent that the provisions on indemnification and contribution contained in the underwriting agreement entered into in connection with the underwritten public offering are in conflict with the foregoing provisions, the provisions in the underwriting agreement shall control.

(f) Unless otherwise superseded by an underwriting agreement entered into in connection with the underwritten public offering, the obligations of the Company and Holders under this Subsection 2.8 shall survive the completion of any offering of Registrable Securities in a registration under this Section 2, and otherwise shall survive the termination of this Agreement.

2.9 Reports Under Exchange Act. With a view to making available to the Holders the benefits of SEC Rule 144 and any other rule or regulation of the SEC that may at any time permit a Holder to sell securities of the Company to the public without registration or pursuant to a registration on Form S-3, the Company shall:

(a) make and keep available adequate current public information, as those terms are understood and defined in SEC Rule 144, at all times after the effective date of the registration statement filed by the Company for the IPO;

(b) use commercially reasonable efforts to file with the SEC in a timely manner all reports and other documents required of the Company under the Securities Act and the Exchange Act (at any time after the Company has become subject to such reporting requirements); and

(c) furnish to any Holder, so long as the Holder owns any Registrable Securities, forthwith upon request (i) to the extent accurate, a written statement by the Company that it has complied with the reporting requirements of SEC Rule 144 (at any time after ninety (90) days after the effective date of the registration statement filed by the Company for the IPO), the Securities Act, and the Exchange Act (at any time after the Company has become subject to such reporting requirements), or that it qualifies as a registrant whose securities may be resold pursuant to Form S-3 (at any time after the Company so qualifies); and (ii) such other information as may be reasonably requested in availing any Holder of any rule or regulation of the SEC that permits the selling of any such securities without registration (at any time after the Company has become subject to the reporting requirements under the Exchange Act) or pursuant to Form S-3 (at any time after the Company so qualifies to use such form).

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2.10 Limitations on Subsequent Registration Rights. From and after the date of this Agreement, the Company shall not, without the prior written consent of the Holders of a majority of the Registrable Securities then outstanding, enter into any agreement with any holder or prospective holder of any securities of the Company that (i) would provide to such holder the right to include securities in any registration other than on a subordinate basis after all Holders have had the opportunity to include in the registration and offering all shares of Registrable Securities that they wish to so include or (ii) allow such holder or prospective holder to initiate a demand for registration of any securities held by such holder or prospective holder; provided that this limitation shall not apply to any additional Investor who becomes a party to this Agreement in accordance with Subsection 6.9.

2.11 “Market Stand-off” Agreement. Each Holder hereby agrees that it will not, without the prior written consent of the managing underwriter, during the period commencing on the date of the final prospectus relating to the IPO, and ending on the date specified by the Company and the managing underwriter (such period not to exceed one hundred eighty (180) days, plus an additional eighteen (18) days to the extent necessary as may be requested by the Company or an underwriter to accommodate regulatory restrictions on (1) the publication or other distribution of research reports and (2) analyst recommendations and opinions, including, but not limited to, the restrictions contained in applicable FINRA rules or NYSE Rule 472(f)(4), or any successor provisions or amendments thereto), (i) lend; offer; pledge; sell; contract to sell; sell any option or contract to purchase; purchase any option or contract to sell; grant any option, right, or warrant to purchase; or otherwise transfer or dispose of, directly or indirectly, any shares of Common Stock or any securities convertible into or exercisable or exchangeable (directly or indirectly) for Common Stock held immediately before the effective date of the registration statement for the IPO or (ii) enter into any swap or other arrangement that transfers to another, in whole or in part, any of the economic consequences of ownership of such securities, whether any such transaction described in clause (i) or (ii) above is to be settled by delivery of Common Stock or other securities, in cash, or otherwise. The foregoing provisions of this Subsection 2.11 shall not apply to the sale of any shares to an underwriter pursuant to an underwriting agreement, or the transfer of any shares to any trust for the direct or indirect benefit of the Holder or the immediate family of the Holder, provided that the trustee of the trust agrees to be bound in writing by the restrictions set forth herein, and provided further that any such transfer shall not involve a disposition for value, and shall be applicable to the Holders only if all officers and directors are subject to the same restrictions and the Company uses commercially reasonable efforts to obtain a similar agreement from all stockholders individually owning more than one percent (1%) of the Company’s outstanding stock (after giving effect to a conversion into Common Stock of all outstanding Preferred Stock). The underwriters in connection with such registration are intended third-party beneficiaries of this Subsection 2.11 and shall have the right, power, and authority to enforce the provisions hereof as though they were a party hereto. Each Holder further agrees to execute such agreements as may be reasonably requested by the underwriters in connection with such registration that are consistent with this Subsection 2.11 or that are necessary to give further effect thereto. Any discretionary waiver or termination of the restrictions of any or all of such agreements by the Company or the underwriters shall apply pro rata to all Holders subject to such agreements, based on the number of shares subject to such agreements.

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2.12 Restrictions on Transfer.

(a) The Preferred Stock and the Registrable Securities shall not be sold, pledged, or otherwise transferred, and the Company shall not recognize and shall issue stop-transfer instructions to its transfer agent with respect to any such sale, pledge, or transfer, except upon the conditions specified in this Agreement, which conditions are intended to ensure compliance with the provisions of the Securities Act. A transferring Holder will cause any proposed purchaser, pledgee, or transferee of the Preferred Stock and the Registrable Securities held by such Holder to agree to take and hold such securities subject to the provisions and upon the conditions specified in this Agreement. Notwithstanding the foregoing, the Company shall not require any transferee of shares pursuant to an effective registration statement or, following the IPO, SEC Rule 144, in each case, to be bound by the terms of this Agreement

(b) Each certificate or instrument representing (i) the Preferred Stock, (ii) the Registrable Securities, and (iii) any other securities issued in respect of the securities referenced in clauses (i) and (ii), upon any stock split, stock dividend, recapitalization, merger, consolidation, or similar event, shall (unless otherwise permitted by the provisions of Subsection 2.12(c)) be stamped or otherwise imprinted with a legend substantially in the following form:

THE SECURITIES REPRESENTED HEREBY HAVE BEEN ACQUIRED FOR INVESTMENT AND HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933. SUCH SHARES MAY NOT BE SOLD, PLEDGED, OR TRANSFERRED IN THE ABSENCE OF SUCH REGISTRATION OR A VALID EXEMPTION FROM THE REGISTRATION AND PROSPECTUS DELIVERY REQUIREMENTS OF SAID ACT.

THE SECURITIES REPRESENTED HEREBY MAY BE TRANSFERRED ONLY IN ACCORDANCE WITH THE TERMS OF AN AGREEMENT BETWEEN THE COMPANY AND THE STOCKHOLDER, A COPY OF WHICH IS ON FILE WITH THE SECRETARY OF THE COMPANY.

The Holders consent to the Company making a notation in its records and giving instructions to any transfer agent of the Restricted Securities in order to implement the restrictions on transfer set forth in this Subsection 2.12.

(c) The holder of each certificate representing Restricted Securities, by acceptance thereof, agrees to comply in all respects with the provisions of this Section 2. Before any proposed sale, pledge, or transfer of any Restricted Securities, unless there is in effect a registration statement under the Securities Act covering the proposed transaction or following the IPO, the transfer is made pursuant to SEC Rule 144, the Holder thereof shall give notice to the Company of such Holder’s intention to effect such sale, pledge, or transfer, provided that no such notice shall be required in connection if the intended sale, pledge or transfer complies with SEC Rule 144. Each such notice shall describe the manner and circumstances of the proposed sale, pledge, or transfer in sufficient detail and, if reasonably requested by the Company, shall be accompanied at such Holder’s expense by either (i) a written opinion of legal counsel who shall, and whose legal opinion shall, be reasonably satisfactory to the Company, addressed to the Company, to the effect that the proposed transaction may be effected without registration under the Securities Act; (ii) a “no action” letter from the SEC to the effect that the proposed sale, pledge, or transfer of such Restricted Securities without registration will not result in a recommendation by the staff of the SEC that action be taken with respect thereto; or (iii) any other evidence reasonably satisfactory to counsel to the Company to the effect that the proposed sale, pledge, or transfer of the Restricted Securities may be effected without registration under the Securities Act,

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whereupon the Holder of such Restricted Securities shall be entitled to sell, pledge, or transfer such Restricted Securities in accordance with the terms of the notice given by the Holder to the Company. The Company will not require such a legal opinion or “no action” letter (x) in any transaction in compliance with SEC Rule 144 or (y) in any transaction in which such Holder distributes Restricted Securities to an Affiliate of such Holder for no consideration; provided that with respect to transfers under the foregoing clause (y), each transferee agrees in writing to be subject to the terms of this Subsection 2.12. Each certificate or instrument evidencing the Restricted Securities transferred as above provided shall bear, except if such transfer is made pursuant to SEC Rule 144, the appropriate restrictive legend set forth in Subsection 2.12(b), except that such certificate shall not bear such restrictive legend if, in the opinion of counsel for such Holder and the Company, such legend is not required in order to establish compliance with any provisions of the Securities Act.

2.13 Termination of Registration Rights. The right of any Holder to request registration or inclusion of Registrable Securities in any registration pursuant to Subsection 2.1 or Subsection 2.2 shall terminate upon the earlier of:

(a) the closing of a Deemed Liquidation Event, as such term is defined in the Restated Certificate, where the consideration received by the Investors is in the form of cash and/or publicly traded securities or where the Investors receive registration rights from the acquiring company or other successor comparable to those set forth in this Section 2; and

(b) such time after consummation of the IPO as SEC Rule 144 or another similar exemption under the Securities Act is available for the sale of all of such Holder’s shares without limitation during a three-month period without registration.

3. Management and Information Rights.

3.1 Delivery of Financial Statements. The Company shall deliver to each Major Investor, provided that the Board of Directors has not reasonably determined that such Major Investor is a competitor of the Company:

(a) as soon as practicable, but in any event within one hundred and eighty (180) days after the end of each fiscal year of the Company, (i) an audited balance sheet as of the end of such year, (ii) audited statements of income and of cash flows for such year, and (iii) an audited statement of stockholders’ equity as of the end of such year, all prepared in accordance with GAAP, and a comparison between (x) the actual amounts as of and for such fiscal year and (y) the comparable amounts for the prior year and as included in the Budget (as defined in Subsection 3.1(d)) for such year;

(b) as soon as practicable, but in any event within forty-five (45) days after the end of each of the first three (3) quarters of each fiscal year of the Company, unaudited statements of income and cash flows for such fiscal quarter, and an unaudited balance sheet as of the end of such fiscal quarter, all prepared in accordance with GAAP (except that such financial statements may (i) be subject to normal year-end audit adjustments and (ii) not contain all notes thereto that may be required in accordance with GAAP);

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(c) as soon as practicable, but in any event within 30 days of the end of each month, an unaudited income statement and statement of cash flows for such month, and an unaudited balance sheet as of the end of such month, all prepared in accordance with GAAP (except that such financial statements may (i) be subject to normal year-end audit adjustments and (ii) not contain all notes thereto that may be required in accordance with GAAP);

(d) as soon as practicable, but in any event thirty (30) days before the end of each fiscal year, a budget and business plan for the next fiscal year (collectively, the “Budget”), prepared on a monthly basis, including balance sheets, income statements, and statements of cash flow for such quarters and, promptly after prepared, any other budgets or revised budgets prepared by the Company;

(e) as soon as practicable, but in any event within 30 days after the end of each month, a statement indicating no change or showing any change in the number of shares of each class and series of capital stock and securities convertible into or exercisable for shares of capital stock outstanding at the end of the period, the Common Stock issuable upon conversion or exercise of any outstanding securities convertible or exercisable for Common Stock and the exchange ratio or exercise price applicable thereto, and the number of shares of issued stock options and stock options not yet issued but reserved for issuance, if any, all in sufficient detail as to permit the Major Investors to calculate their respective percentage equity ownership in the Company, and certified by the chief financial officer or chief executive officer of the Company as being true, complete, and correct.

(f) such other information relating to the financial condition, business, prospects, or corporate affairs of the Company as any Major Investor may from time to time reasonably request; provided, however, that the Company shall not be obligated under this Subsection 3.1 to provide information (i) that the Company reasonably determines in good faith to be a trade secret or confidential information (unless covered by an enforceable confidentiality agreement, in a form acceptable to the Company) or (ii) the disclosure of which would adversely affect the attorney-client privilege between the Company and its counsel.

If, for any period, the Company has any subsidiary whose accounts are consolidated with those of the Company, then in respect of such period the financial statements delivered pursuant to the foregoing sections shall be the consolidated financial statements of the Company and all such consolidated subsidiaries.

Notwithstanding anything else in this Subsection 3.1 to the contrary, the Company may cease providing the information set forth in this Subsection 3.1 during the period starting with the date sixty (60) days before the Company’s good-faith estimate of the date of filing of a registration statement if it reasonably concludes it must do so to comply with the SEC rules applicable to such registration statement and related offering; provided that the Company’s covenants under this Subsection 3.1 shall be reinstated at such time as the Company is no longer actively employing its commercially reasonable efforts to cause such registration statement to become effective.

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3.2 Inspection. The Company shall permit each Major Investor (provided that the Board of Directors has not reasonably determined that such Major Investor is a competitor of the Company), at such Major Investor’s expense, to visit and inspect the Company’s properties; examine its books of account and records; and discuss the Company’s affairs, finances, and accounts with its officers, during normal business hours of the Company as may be reasonably requested by the Major Investor; provided, however, that the Company shall not be obligated pursuant to this Subsection 3.2 to provide access to any information that it reasonably and in good faith considers to be a trade secret or confidential information (unless covered by an enforceable confidentiality agreement, in form acceptable to the Company) or the disclosure of which would adversely affect the attorney-client privilege between the Company and its counsel.

3.3 Termination of Information. The covenants set forth in Subsection 3.1 and Subsection 3.2 shall terminate and be of no further force or effect (i) immediately before the consummation of the IPO, (ii) when the Company first becomes subject to the periodic reporting requirements of Section 12(g) or 15(d) of the Exchange Act, or (iii) upon the closing of a Deemed Liquidation Event, as such term is defined in the Restated Certificate, whichever event occurs first; provided, that, with respect to clause (iii), the covenants set forth in Section 3.1 and 3.2 shall only terminate if the consideration received by the Investors in such Deemed Liquidation Event is in the form of cash and/or publicly traded securities unless the Major Investors receive financial information from the acquiring company or other successor to the Company comparable to those set forth in Section 3.1.

3.4 Confidentiality. Each Investor agrees that such Investor will keep confidential and will not disclose, divulge, or use for any purpose (other than to monitor or make decisions with respect to its investment in the Company) any confidential information obtained from the Company pursuant to the terms of this Agreement (including notice of the Company’s intention to file a registration statement), unless such confidential information (a) is known or becomes known to the public in general (other than as a result of a breach of this Subsection 3.4 by such Investor), (b) is or has been independently developed or conceived by the Investor without use of the Company’s confidential information, or (c) is or has been made known or disclosed to the Investor by a third party without a breach of any obligation of confidentiality such third party may have to the Company; provided, however, that an Investor may disclose confidential information (i) to its attorneys, accountants, consultants, and other professionals to the extent reasonably necessary to obtain their services in connection with monitoring its investment in the Company; (ii) to any prospective purchaser of any Registrable Securities from such Investor, if such prospective purchaser agrees to be bound by the provisions of this Subsection 3.4; (iii) to any existing or prospective Affiliate, partner, member, stockholder, or wholly owned subsidiary of such Investor in the ordinary course of business, provided that such Investor informs such Person that such information is confidential and directs such Person to maintain the confidentiality of such information; or (iv) as may otherwise be required by law, regulation, rule, court order or subpoena, provided that the Investor promptly notifies the Company of such disclosure and takes reasonable steps to minimize the extent of any such required disclosure.

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3.5 Critical Technology Matters.

(a) To the extent (i) any pre-existing products or services provided by the Company are re-categorized by the U.S. government as a critical technology within the meaning of Section 721 of the Defense Production Act of 1950, as amended, including all implementing regulations thereof (the “DPA”), or would reasonably be considered to constitute the design, fabrication, development, testing, production or manufacture of a critical technology after a re-categorization of selected technologies by the U.S. government, or (ii) after execution of the Purchase Agreement, the Company engages in any activity that could reasonably be considered to constitute the design, fabrication, development, testing, production or manufacture of a critical technology within the meaning of the DPA, the Company shall promptly notify the Investors of such change in the categorization of its products or services.

(b) If and only if (i) the Committee on Foreign Investment in the United States or any member agency thereof acting in such capacity (“CFIUS”) requests or requires that any Investor or the Company file a notice or declaration with CFIUS pursuant to the DPA with respect to such Investor’s investment in the Company (the “Covered Transactions”) or (ii) such Investor or the Company reasonably determines that a filing with CFIUS with respect to the Covered Transactions is advisable or required by applicable law, then in either case, (i) or (ii): (x) the Company and each Investor shall, and shall cause its Affiliates to, cooperate with the other parties hereto and shall promptly file a CFIUS filing in the requested, required or advisable form in accordance with the DPA; (y) the Company and each Investor shall, and shall cause its Affiliates to, use reasonable best efforts to obtain, as applicable, the CFIUS Satisfied Condition (as defined in the Restated Certificate); and (z) the Company shall provide notice of clause (i) or (ii) to the Major Investors. For the avoidance of doubt, each such Investor shall have no obligation to accept or take any action, condition or restriction with respect to the Covered Transactions in order to achieve the CFIUS Satisfied Condition.

4. Rights to Future Stock Issuances.

4.1 Right of First Offer. Subject to the terms and conditions of this Subsection 4.1 and applicable securities laws, if the Company proposes to offer or sell any New Securities, the Company shall first offer such New Securities to each Major Investor. A Major Investor shall be entitled to apportion the right of first offer hereby granted to it in such proportions as it deems appropriate, among (i) itself and (ii) its Affiliates; provided that, each such Affiliate (x) is not a competitor of the Company as reasonably determined by the Board of Directors, unless such party’s purchase of New Securities is otherwise consented to by the Board of Directors, (y) agrees to enter into this Agreement and each of the Third Amended and Restated Voting Agreement and Second Amended and Restated Right of First Refusal and Co-Sale Agreement of even date herewith among the Company, the Investors and the other parties named therein, as an “Investor” under each such agreement (provided that, any competitor of the Company as reasonably determined by the Board of Directors shall not be entitled to any rights as an Investor under Subsections 3.1, 3.2 or 4.1 hereof), and (z) agrees to purchase at least such number of New Securities as are allocable hereunder to the Investor holding the fewest number of Preferred Stock and any other Derivative Securities. For purposes of this Agreement, neither Celgene Corporation nor its Affiliates are “a competitor of the Company”.

(a) The Company shall give notice (the “Offer Notice”) to each Major Investor, stating (i) its bona fide intention to offer such New Securities, (ii) the number of such New Securities to be offered, and (iii) the price and terms, if any, upon which it proposes to offer such New Securities.

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(b) By notification to the Company within twenty (20) days after the Offer Notice is given, each Major Investor may elect to purchase or otherwise acquire, at the price and on the terms specified in the Offer Notice, up to that portion of such New Securities which equals the proportion that the Common Stock that are not Default Conversion Shares then held by such Major Investor (including all shares of Common Stock then issuable (directly or indirectly) upon conversion and/or exercise, as applicable, of the Preferred Stock and any other Derivative Securities then held by such Investor) bears to the total Common Stock of the Company then outstanding (assuming full conversion and/or exercise, as applicable, of all Preferred Stock and other Derivative Securities and excluding any Default Conversion Shares). At the expiration of such twenty (20) day period, the Company shall promptly notify each Major Investor that elects to purchase or acquire all the shares available to it (each, a “Fully Exercising Investor”) of any other Major Investor’s failure to do likewise. During the ten (10) day period commencing after the Company has given such notice, each Fully Exercising Investor may, by giving notice to the Company, elect to purchase or acquire, in addition to the number of shares specified above, up to that portion of the New Securities for which Major Investors were entitled to subscribe but that were not subscribed for by the Major Investors which is equal to the proportion that the Common Stock that are not Default Conversion Shares issued and held, or issuable (directly or indirectly) upon conversion and/or exercise, as applicable, of Preferred Stock and any other Derivative Securities then held, by such Fully Exercising Investor bears to the Common Stock, that are not Default Conversion Shares, issued and held, or issuable (directly or indirectly) upon conversion and/or exercise, as applicable, of the Preferred Stock and any other Derivative Securities then held, by all Fully Exercising Investors who wish to purchase such unsubscribed shares. The closing of any sale pursuant to this Subsection 4.1(b) shall occur within the later of forty-five (45) days of the date that the Offer Notice is given and the date of initial sale of New Securities pursuant to Subsection 4.1(c).

(c) If all New Securities referred to in the Offer Notice are not elected to be purchased or acquired as provided in Subsection 4.1(b), the Company may, during the ninety (90) day period following the expiration of the periods provided in Subsection 4.1(b), offer and sell the remaining unsubscribed portion of such New Securities to any Person or Persons at a price not less than, and upon terms no more favorable to the offeree than, those specified in the Offer Notice. If the Company does not enter into an agreement for the sale of the New Securities within such period, or if such agreement is not consummated within thirty (30) days of the execution thereof, the right provided hereunder shall be deemed to be revived and such New Securities shall not be offered unless first reoffered to the Major Investors in accordance with this Subsection 4.1.

(d) The right of first offer in this Subsection 4.1 shall not be applicable to (i) Exempted Securities (as defined in the Restated Certificate); and (ii) shares of Common Stock issued in the IPO.

(e) Notwithstanding any provision hereof to the contrary, in lieu of complying with the provisions of this Subsection 4.1, the Company may elect to give notice to the Major Investors within thirty (30) days after the issuance of New Securities. Such notice shall describe the type, price, and terms of the New Securities. Each Investor shall have twenty (20) days from the date notice is given to elect to purchase up to the number of New Securities that would, if purchased by such Major Investor, maintain such Major Investor’s percentage- ownership position, calculated as set forth in Subsection 4.1(b) before giving effect to the issuance of such New Securities. The closing of such sale shall occur within sixty (60) days of the date notice is given to the Major Investors.

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4.2 Termination. The covenants set forth in Subsection 4.1 shall terminate and be of no further force or effect (i) immediately before the consummation of the IPO, or (ii) upon a Deemed Liquidation Event, as such term is defined in the Restated Certificate, whichever event occurs first.

4.3 Special Mandatory Conversion. For purposes of the Restated Certificate, only those Investors set forth on Schedule B attached hereto shall constitute “Key Investors” (as defined and used in Article IV of the Restated Certificate).

5. Additional Covenants.

5.1 Insurance. The Company shall use its commercially reasonable efforts to maintain Directors and Officers liability insurance covering the Company’s directors and officers, with a minimum coverage amount of $3 million and on terms and conditions satisfactory to the Board of Directors, including the Requisite Directors, until such time as the Board of Directors determines that such insurance should be discontinued. In the event the Company merges with another entity and the Company is not the surviving corporation, or transfers all of its assets, proper provisions shall be made so that successors of the Company assume the Company’s obligations with respect to indemnification of directors.

5.2 Employee Agreements. The Company will cause (i) each person now or hereafter employed by it or by any subsidiary (or engaged by the Company or any subsidiary as a consultant/independent contractor) to enter into a nondisclosure and proprietary rights assignment agreement and (ii) each Key Employee (as defined in the Purchase Agreement) to enter into a one (1) year noncompetition and nonsolicitation agreement, substantially in the form previously approved by the Board of Directors (a copy of which has been made available to Investors). In addition, the Company shall not amend, modify, terminate, waive, or otherwise alter, in whole or in part, any of the above-referenced agreements or any restricted stock agreement between the Company and any employee, without the consent of the Requisite Directors.

5.3 Employee Stock. Unless otherwise approved by the Board of Directors, including the Requisite Directors, all future employees and consultants of the Company who purchase, receive options to purchase, or receive awards of shares of the Company’s capital stock after the date hereof shall be required to execute restricted stock or option agreements, as applicable, providing for (i) vesting of shares over a four (4) year period, with the first twenty- five percent (25%) of such shares vesting following twelve (12) months of continued employment or service, and the remaining shares vesting in equal monthly installments over the following thirty-six (36) months, and (ii) a market stand-off provision substantially similar to that in Subsection 2.11. In addition, unless otherwise approved by the Board of Directors, including the Requisite Directors, the Company shall retain a “right of first refusal” on employee transfers until the Company’s IPO and shall have the right to repurchase unvested shares at the lesser of cost or fair market value of any unvested shares held by such holder upon termination of employment of a holder of restricted stock.

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5.4 Qualified Small Business Stock. The Company shall use commercially reasonable efforts to cause the shares of Preferred Stock issued on or before September 27, 2019, as well as any shares into which such shares are converted, within the meaning of Section 1202(f) of the Internal Revenue Code (the “Code”), to constitute “qualified small business stock” as defined in Section 1202(c) of the Code; provided, however, that such requirement shall not be applicable if the Board of Directors of the Company determines, in its good-faith business judgment, that such qualification is inconsistent with the best interests of the Company. The Company shall submit to its stockholders (including the Investors) and to the Internal Revenue Service any reports that may be required under Section 1202(d)(1)(C) of the Code and the regulations promulgated thereunder. In addition, within twenty (20) business days after any Investor’s written request therefor, the Company shall, at its option, either (i) deliver to such Investor a written statement indicating whether (and what portion of) such Investor’s interest in the Company constitutes “qualified small business stock” as defined in Section 1202(c) of the Code or (ii) deliver to such Investor such factual information in the Company’s possession as is reasonably necessary to enable such Investor to determine whether (and what portion of) such Investor’s interest in the Company constitutes “qualified small business stock” as defined in Section 1202(c) of the Code.

5.5 Matters Requiring Investor Director Approval. So long as the holders of Preferred Stock are entitled to elect a Director, the Company hereby covenants and agrees with each of the Investors that it shall not, without approval of the Board of Directors, which approval must include the affirmative vote of the Requisite Directors:

(a) form any subsidiary or enter into a joint venture;

(b) make, or permit any subsidiary to make, any loan or advance to, or own any stock or other securities of, any subsidiary or other corporation, partnership, or other entity unless it is wholly owned by the Company;

(c) make, or permit any subsidiary to make, any loan or advance to any Person, including, without limitation, any employee or director of the Company or any subsidiary, except advances and similar expenditures in the ordinary course of business or under the terms of an employee stock or option plan approved by the Board of Directors;

(d) guarantee or assume, directly or indirectly, or permit any subsidiary to guarantee or assume, directly or indirectly, any indebtedness except for trade accounts of the Company or any subsidiary arising in the ordinary course of business;

(e) make any investment inconsistent with any investment policy approved by the Board of Directors;

(f) create or authorize the creation of any indebtedness, including without limitation any debt security, if the Company’s aggregate indebtedness would exceed $500,000 to the extent not already included in a Budget approved by the Board of Directors, other than trade credit incurred in the ordinary course of business;

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(g) otherwise enter into or be a party to any transaction with any director, officer, or employee of the Company or any “associate” (as defined in Rule 12b-2 promulgated under the Exchange Act) of any such Person, except for transactions contemplated by this Agreement, the Purchase Agreement, and transactions resulting in payments to or by the Company in the form of compensation or benefits in the ordinary course of business;

(h) hire, fire, or change the compensation of the Chief Executive Officer, President, Chief Scientific Officer, Chief Medical Officer, or Chief Financial Officer, including approving or modifying any option grants or stock awards;

(i) change the principal business of the Company, enter new lines of business, or exit the current line of business (provided that a change in Company’s lead candidate(s) or back-up candidate(s) in connection with oncology-related diseases and indications shall not be deemed to be a change of entering a new line of business or exiting a current line of business requiring the approval described in this Section 5.5);

(j) create or hold capital stock in any subsidiary that is not a wholly-owned subsidiary or dispose of any subsidiary stock or all or substantially all of any subsidiary assets;

(k) acquire all of the equity securities of another entity, or all or substantially all of the assets of another entity;

(l) enter into any corporate strategic relationship involving the payment, contribution or assignment by the Company or to the Company of assets greater than $250,000;

(m) sell, assign, license, pledge, or encumber material technology or intellectual property, other than licenses granted in the ordinary course of business; and

(n) enter into an agreement to do any of the foregoing.

5.6 Board Matters. Unless otherwise determined by the vote of a majority of the directors then in office, the Board of Directors shall meet at least quarterly in accordance with an agreed-upon schedule. The Company shall reimburse the directors for all reasonable out-of-pocket travel expenses incurred (consistent with the Company’s travel policy) in connection with attending meetings of the Board of Directors. Each committee of the Board of Directors shall comprise no fewer than three members.

5.7 Successor Indemnification. If the Company or any of its successors or assignees consolidates with or merges into any other Person and is not the continuing or surviving corporation or entity of such consolidation or merger or the Company or any subsidiary of the Company sells or otherwise transfers all or substantially all of the assets or intellectual property of the Company, then to the extent necessary, proper provision shall be made so that the successors and assignees of the Company assume the obligations of the Company with respect to indemnification of members of the Board of Directors as in effect immediately before such transaction, whether such obligations are contained in the Company’s Bylaws, the Restated Certificate, or elsewhere, as the case may be.

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5.8 Indemnification Matters. The Company hereby acknowledges that the Preferred Directors may have certain rights to indemnification, advancement of expenses and/or insurance provided by one or more of the Investors and certain of their affiliates (collectively, the “Preferred Director Indemnitors”). The Company hereby agrees (a) that it is the indemnitor of first resort (i.e., its obligations to any such Preferred Director are primary and any obligation of the Preferred Director Indemnitors to advance expenses or to provide indemnification for the same expenses or liabilities incurred by such Preferred Director are secondary), (b) that it shall be required to advance the full amount of expenses incurred by such Preferred Director and shall be liable for the full amount of all expenses, judgments, penalties, fines and amounts paid in settlement by or on behalf of any such Preferred Director to the extent legally permitted and as required by the Restated Certificate or Bylaws of the Company (or any agreement between the Company and such Preferred Director), without regard to any rights such Preferred Director may have against the Preferred Director Indemnitors, and, (c) that it irrevocably waives, relinquishes and releases the Preferred Director Indemnitors from any and all claims against the Preferred Director Indemnitors for contribution, subrogation or any other recovery of any kind in respect thereof. The Company further agrees that no advancement or payment by the Preferred Director Indemnitors on behalf of any such Preferred Director with respect to any claim for which such Preferred Director has sought indemnification from the Company shall affect the foregoing and the Preferred Director Indemnitors shall have a right of contribution and/or be subrogated to the extent of such advancement or payment to all of the rights of recovery of such Preferred Director against the Company.

5.9 Termination of Covenants. The covenants set forth in this Section 5, except for Subsection 5.7, shall terminate and be of no further force or effect (i) immediately before the consummation of the IPO, (ii) when the Company first becomes subject to the periodic reporting requirements of Section 12(g) or 15(d) of the Exchange Act, or (iii) upon a Deemed Liquidation Event, as such term is defined in the Restated Certificate, whichever event occurs first.

5.10 Right to Conduct Activities. The Company hereby acknowledges that (a) each of Venrock Associates VII, L.P., Venrock Partners VII, L.P. (collectively, along with their affiliates, “Venrock”), Droia Invest II SCSP (together with its affiliates, “Droia”), Lightstone Ventures II, L.P., Lightstone Ventures II (A), L.P. (collectively, along with their affiliates, “Lightstone”), Novo (together with their affiliates), RA Capital Funds (together with their affiliates), Ally Bridge MedAlpha Master Fund L.P. (together with its affiliates, “Ally Bridge”), Janus Henderson Global Life Sciences Fund, Janus Henderson Biotech Innovation Master Fund Limited, Janus Henderson Capital Funds plc on behalf of its series Janus Henderson Global Life Sciences Fund and Janus Henderson Horizon Fund - Biotechnology Fund (collectively, along with their affiliates, “Janus”), Baker Brothers Life Sciences, L.P. and 667, L.P. (collectively, along with their affiliates, “Baker Brothers”) and CaaS Opportunity LLC (together with its affiliates, “CaaS”) (“Fund Investors”) are professional investment funds, and as such invest capital in numerous portfolio companies, some of which may be deemed competitive with the Company’s business (as currently conducted or as currently propose to be conducted); and (b) Celgene Corporation (“Celgene”) invests capital in other companies, some of which may be deemed competitive with the Company’s business (as currently conducted or as currently proposed to be conducted). The Company hereby agrees that, to the extent permitted under applicable law, Fund Investors and Celgene shall not be liable to the Company for any claim arising out of, or based upon, (i) the investment by a Fund Investor or Celgene in any entity competitive with the

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Company, or (ii) actions taken by any partner, officer or other representative of a Fund Investor or Celgene to assist any such competitive company, whether or not such action was taken as a member of the board of directors of such competitive company or otherwise, and whether or not such action has a detrimental effect on the Company; provided, however, that the foregoing shall not relieve (x) a Fund Investor or Celgene from liability associated with the unauthorized disclosure of the Company’s confidential information obtained pursuant to this Agreement, or any other agreement (y) any director or officer of the Company from any liability associated with his or her fiduciary duties to the Company or (z) Celgene from a breach of any other agreement with the Company. For the avoidance of doubt, no Fund Investor shall be deemed “a competitor of the Company” for purposes of Subsections 3.1, 3.2 or 4.1.

5.11 Restrictions on Publicity. The Company shall not use the name of Novo or its Affiliates, or refer to Novo or its Affiliates, directly or indirectly, in connection with Novo’s or its Affiliates’ relationship, agreements or arrangements with the Company in any advertisement, press release, professional or trade publication, marketing materials or otherwise to the general public or in any other manner, except (i) as may be required by law, (ii) on a confidential basis to potential financing sources, including lenders, investors, investment bankers or acquirors but only as to the fact of Novo’s equity investment in the Company and documentation relating thereto, (iii) on a confidential basis to the Company’s lawyers, contractors, accountants and other advisors who have a need to have access and knowledge of such information, or (iv) with Novo’s, as applicable, prior written consent, which consent may be withheld in its sole discretion; provided that (i) the parties anticipate that there will be a mutually-agreed press release announcing the closing of the transactions contemplated in the Purchase Agreement and (ii) following the public announcement contemplated in clause (i), the Company may confirm that Novo are investors in the Company (but not the amount or terms thereof) in a form of disclosure that has been previously approved by Novo, as applicable.

5.12 Expenses of Counsel.    In the event of a transaction which is a Sale of the Company (as defined in the Third Amended and Restated Voting Agreement of even date herewith among the Company, the Investors and the other parties named therein), the reasonable fees and disbursements, not to exceed $30,000 in the aggregate, of one counsel for the Major Investors (“Investor Counsel”) in their capacities as stockholders, shall be borne and paid by the Company. At the outset of considering a transaction which, if consummated would constitute a Sale of the Company, the Company shall obtain the ability to share with the Investor Counsel (and such counsel’s clients) and shall share the confidential information (including, without limitation, the initial and all subsequent drafts of memoranda of understanding, letters of intent and other transaction documents and related noncompete, employment, consulting and other compensation agreements and plans) pertaining to and memorializing any of the transactions which, individually or when aggregated with others would constitute the Sale of the Company. The Company shall be obligated to share (and cause the Company’s counsel and investment bankers to share) such materials when distributed to the Company’s executives and/or any one or more of the other parties to such transaction(s). In the event that Investor Counsel deems it appropriate, in its reasonable discretion, to enter into a joint defense agreement or other arrangement to enhance the ability of the parties to protect their communications and other reviewed materials under the attorney client privilege, the Company shall, and shall direct its counsel to, execute and deliver to Investor Counsel and its clients such an agreement in form and substance reasonably acceptable to Investor Counsel. In the event that one or more of the other party or parties to such transactions require the

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clients of Investor Counsel to enter into a confidentiality agreement and/or joint defense agreement in order to receive such information, then the Company shall share whatever information can be shared without entry into such agreement and shall, at the same time, in good faith work expeditiously to enable Investor Counsel and its clients to negotiate and enter into the appropriate agreement(s) without undue burden to the clients of Investor Counsel.

5.13 Anti-Harassment Policy. The Company shall, within sixty (60) days following the Closing (as defined in the Purchase Agreement), adopt and thereafter maintain in effect (i) a Code of Conduct governing appropriate workplace behavior and (ii) an Anti-Harassment and Discrimination Policy prohibiting discrimination and harassment at the Company. Such policy shall be reviewed and approved by the Board of Directors.

5.14 Real Property Holding Corporation. Promptly following (and in any event within ten (10) days after receipt of) written request by an Investor, the Company shall provide such Investor with a written statement informing such Investor whether such Investor’s interest in the Company constitutes a United States real property interest. The Company’s determination shall comply with the requirements of Treasury Regulation Section 1.897-2(h)(1) or any successor regulation, and the Company shall provide timely notice to the Internal Revenue Service, in accordance with and to the extent required by Treasury Regulation Section 1.897-2(h)(2) or any successor regulation, that such statement has been made. The Company’s obligation to furnish such written statement shall continue notwithstanding the fact that a class of the Company’s stock may be regularly traded on an established securities market or the fact that there is no Preferred Stock then outstanding.

6. Miscellaneous.

6.1 Successors and Assigns. The rights under this Agreement may be assigned (but only with all related obligations) by a Holder to a transferee of Registrable Securities that (i) is an Affiliate of a Holder; (ii) is a Holder’s Immediate Family Member or trust for the benefit of an individual Holder or one or more of such Holder’s Immediate Family Members; or (iii) after such transfer, holds at least twenty-five percent (25%) of the shares of Registrable Securities held by the Holder at the time Holder first entered in this Agreement (subject to appropriate adjustment for stock splits, stock dividends, combinations, and other recapitalizations); provided, however, that (x) the Company is, within a reasonable time after such transfer, furnished with written notice of the name and address of such transferee and the Registrable Securities with respect to which such rights are being transferred; and (y) such transferee agrees in a written instrument delivered to the Company to be bound by and subject to the terms and conditions of this Agreement, including the provisions of Subsection 2.11. For the purposes of determining the number of shares of Registrable Securities held by a transferee, the holdings of a transferee (1) that is an Affiliate or stockholder of a Holder; (2) who is a Holder’s Immediate Family Member; or (3) that is a trust for the benefit of an individual Holder or such Holder’s Immediate Family Member shall be aggregated together and with those of the transferring Holder; provided further that all transferees who would not qualify individually for assignment of rights shall have a single attorney-in-fact for the purpose of exercising any rights, receiving notices, or taking any action under this Agreement. The terms and conditions of this Agreement inure to the benefit of and are binding upon the respective successors and permitted assignees of the parties. Nothing in this Agreement, express or implied, is intended to confer upon any party other than the parties hereto or their respective successors and permitted assignees any rights, remedies, obligations or liabilities under or by reason of this Agreement, except as expressly provided herein.

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6.2 Governing Law. This Agreement shall be governed by the internal law of the State of Delaware, without regard to conflict of law principles that would result in the application of any law other than the law of the State of Delaware.

6.3 Counterparts. This Agreement may be executed in two (2) or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via electronic mail (including pdf or any electronic signature complying with the U.S. federal ESIGN Act of 2000, e.g., www.docusign.com) or other transmission method and any counterpart so delivered shall be deemed to have been duly and validly delivered and be valid and effective for all purposes.

6.4 Titles and Subtitles. The titles and subtitles used in this Agreement are for convenience only and are not to be considered in construing or interpreting this Agreement.

6.5 Notices. All notices and other communications given or made pursuant to this Agreement shall be in writing and shall be deemed effectively given upon the earlier of actual receipt or: (i) personal delivery to the party to be notified; (ii) when sent, if sent by electronic mail during the recipient’s normal business hours, and if not sent during normal business hours, then on the recipient’s next business day; (iii) five (5) days after having been sent by registered or certified mail, return receipt requested, postage prepaid; or (iv) one (1) business day after the business day of deposit with a nationally recognized overnight courier, freight prepaid, specifying next-day delivery, with written verification of receipt. All communications shall be sent to the respective parties at their addresses as set forth on Schedule A or Schedule B hereto, as applicable, or to the principal office of the Company and to the attention of the Chief Executive Officer, in the case of the Company, or to such email address, or address as subsequently modified by written notice given in accordance with this Subsection 6.5. If notice is given to the Company, a copy shall also be sent to Marc Rubenstein, Esq., Ropes & Gray LLP, Prudential Tower, 800 Boylston Street, Boston, MA 02119-3600; if notice is given to The David and Barbara Roux Trust udt 8/11/99, a copy shall also be given to Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, One Financial Place, Boston, MA 02111, Attn: Michael Fantozzi; if notice is given to Celgene Corporation, a copy shall also be given to Assistant Secretary, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901; if notice is given to Venrock, a copy shall also be given to Wilson Sonsini Goodrich & Rosati, P.C., 650 Page Mill Road, Palo Alto, California 94304, Attn: Steven E. Bochner; if notice is given to Novo, a copy (which shall not constitute notice) shall also be given to Wilson Sonsini Goodrich & Rosati P.C., 12235 El Camino Real, San Diego, California 92130, Attention: Dan Koeppen, Esq; if notice is given to RA Capital Fund, a copy (which shall not constitute notice) shall also be given to Cooley LLP, 500 Boylston Street, Floor 14, Boston, MA 02116, Attention: Ryan S. Sansom; if notice is given to Janus, a copy (which shall not constitute notice) shall also be given to Stradley Ronon Stevens & Young, LLP, 457 Haddonfield Road, Suite 100, Cherry Hill, NJ 08002-2223, Attention: Daniel Knox; and if notice is given to Ally Bridge, a copy (which shall not constitute notice) shall also be given to Latham & Watkins, LLP, 200 Clarendon Street, Boston, MA 02116, Attention: Peter Handrinos.

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6.6 Amendments and Waivers. Any term of this Agreement may be amended and the observance of any term of this Agreement may be waived (either generally or in a particular instance, and either retroactively or prospectively) only with the written consent of the Company and the holders of a majority of the Registrable Securities then outstanding; provided that the Company may in its sole discretion waive compliance with Subsection 2.12(c) (and the Company’s failure to object promptly in writing after notification of a proposed assignment allegedly in violation of Subsection 2.12(c) shall be deemed to be a waiver); and provided further that any provision hereof may be waived by any waiving party on such party’s own behalf, without the consent of any other party. Notwithstanding the foregoing, (a) this Agreement may not be amended or terminated and the observance of any term hereof may not be waived with respect to any Investor without the written consent of such Investor, unless such amendment, termination, or waiver applies to all Investors in the same fashion (it being agreed that a waiver of the provisions of Section 4 with respect to a particular transaction shall be deemed to apply to all Investors in the same fashion if such waiver does so by its terms, notwithstanding the fact that certain Investors may nonetheless, by agreement with the Company, purchase securities in such transaction), (b) Subsections 3.5, 5.10, 5.11, 6.11, 6.15, this clause (b) of this Subsection 6.6 and the definition of Affiliate as it pertains to Novo may not be amended or terminated and the observance of any term may not be waived without the written consent of Novo. The Company shall give prompt notice of any amendment or termination hereof or waiver hereunder to any party hereto that did not consent in writing to such amendment, termination, or waiver. Any amendment, termination, or waiver effected in accordance with this Subsection 6.6 shall be binding on all parties hereto, regardless of whether any such party has consented thereto. No waivers of or exceptions to any term, condition, or provision of this Agreement, in any one or more instances, shall be deemed to be or construed as a further or continuing waiver of any such term, condition, or provision.

6.7 Severability. In case any one or more of the provisions contained in this Agreement is for any reason held to be invalid, illegal or unenforceable in any respect, such invalidity, illegality, or unenforceability shall not affect any other provision of this Agreement, and such invalid, illegal, or unenforceable provision shall be reformed and construed so that it will be valid, legal, and enforceable to the maximum extent permitted by law.

6.8 Aggregation of Stock. All shares of Registrable Securities held or acquired by Affiliates shall be aggregated together for the purpose of determining the availability of any rights under this Agreement and such Affiliated persons may apportion such rights as among themselves in any manner they deem appropriate.

6.9 Additional Investors. Notwithstanding anything to the contrary contained herein, if the Company issues additional shares of the Company’s Preferred Stock after the date hereof, any purchaser of such shares of Preferred Stock may become a party to this Agreement by executing and delivering an additional counterpart signature page to this Agreement, and thereafter shall be deemed an “Investor” for all purposes hereunder. No action or consent by the Investors shall be required for such joinder to this Agreement by such additional Investor, so long as such additional Investor has agreed in writing to be bound by all of the obligations as an “Investor” hereunder.

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6.10 Entire Agreement. This Agreement (including any Schedules and Exhibits hereto) constitutes the full and entire understanding and agreement among the parties with respect to the subject matter hereof, and any other written or oral agreement relating to the subject matter hereof existing between the parties is expressly canceled. Upon the effectiveness of this Agreement, the Prior Agreement shall be deemed amended and restated and superseded and replaced in its entirety by this Agreement, and shall be of no further force or effect.

6.11 Dispute Resolution. The parties (a) hereby irrevocably and unconditionally submit to the jurisdiction of the Court of Chancery of the State of Delaware and to the jurisdiction of the United States District Court for the District of Delaware (the “Courts”) for the purpose of any suit, action or other proceeding arising out of or based upon this Agreement, (b) agree not to commence any suit, action or other proceeding arising out of or based upon this Agreement except in the Courts, and (c) hereby waive, and agree not to assert, by way of motion, as a defense, or otherwise, in any such suit, action or proceeding, any claim that it is not subject personally to the jurisdiction of the Courts, that its property is exempt or immune from attachment or execution, that the suit, action or proceeding is brought in an inconvenient forum, that the venue of the suit, action or proceeding is improper or that this Agreement or the subject matter hereof may not be enforced in or by the Courts.

WAIVER OF JURY TRIAL: EACH PARTY HEREBY WAIVES ITS RIGHTS TO A JURY TRIAL OF ANY CLAIM OR CAUSE OF ACTION BASED UPON OR ARISING OUT OF THIS AGREEMENT, THE OTHER TRANSACTION DOCUMENTS, THE SECURITIES OR THE SUBJECT MATTER HEREOF OR THEREOF. THE SCOPE OF THIS WAIVER IS INTENDED TO BE ALL-ENCOMPASSING OF ANY AND ALL DISPUTES THAT MAY BE FILED IN ANY COURT AND THAT RELATE TO THE SUBJECT MATTER OF THIS TRANSACTION, INCLUDING, WITHOUT LIMITATION, CONTRACT CLAIMS, TORT CLAIMS (INCLUDING NEGLIGENCE), BREACH OF DUTY CLAIMS, AND ALL OTHER COMMON LAW AND STATUTORY CLAIMS. THIS SECTION HAS BEEN FULLY DISCUSSED BY EACH OF THE PARTIES HERETO AND THESE PROVISIONS WILL NOT BE SUBJECT TO ANY EXCEPTIONS. EACH PARTY HERETO HEREBY FURTHER WARRANTS AND REPRESENTS THAT SUCH PARTY HAS REVIEWED THIS WAIVER WITH ITS LEGAL COUNSEL, AND THAT SUCH PARTY KNOWINGLY AND VOLUNTARILY WAIVES ITS JURY TRIAL RIGHTS FOLLOWING CONSULTATION WITH LEGAL COUNSEL.

Each party will bear its own costs in respect of any disputes arising under this Agreement. Each of the parties to this Agreement consents to personal jurisdiction for any equitable action sought in the U.S. District Court for the District of Delaware or any court of the State of Delaware having subject matter jurisdiction.

6.12 Delays or Omissions. No delay or omission to exercise any right, power, or remedy accruing to any party under this Agreement, upon any breach or default of any other party under this Agreement, shall impair any such right, power, or remedy of such nonbreaching or nondefaulting party, nor shall it be construed to be a waiver of or acquiescence to any such breach or default, or to any similar breach or default thereafter occurring, nor shall any waiver of any single breach or default be deemed a waiver of any other breach or default theretofore or thereafter occurring. All remedies, whether under this Agreement or by law or otherwise afforded to any party, shall be cumulative and not alternative.

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6.13 Acknowledgment. The Company acknowledges that the Investors are in the business of venture capital investing and therefore review the business plans and related proprietary information of many enterprises, including enterprises which may have products or services which compete directly or indirectly with those of the Company. Nothing in this Agreement shall preclude or in any way restrict the Investors from investing or participating in any particular enterprise whether or not such enterprise has products or services which compete with those of the Company.

6.14 Default. In the event of a Special Mandatory Conversion (as defined in the Restated Certificate) by an Investor, such Investor shall lose all of its rights under this Agreement with respect to the Default Conversion Shares, except with respect to Sections 5.8 and 5.10. For the avoidance of doubt, each Investor shall remain subject to all of the obligations of an Investor hereunder, including, without limitation, Sections 2.11, 2.12, and 3.4.

6.15 Limitation of Liability; Freedom to Operate Affiliates. The total liability, in the aggregate, of each of the Investors and its respective Affiliates, officers, directors, employees and agents, for any and all claims, losses, costs or damages, including attorneys’ and accountants’ fees and expenses and costs of any nature whatsoever or claims or expenses resulting from or in any way related to this Agreement from any cause or causes shall be several and not joint with the other Investors and in the case of each Investor shall not exceed the total purchase price paid to the Company by the Investor for the shares of capital stock of the Company purchased by the Investor. It is intended that this limitation apply to any and all liability or cause of action however alleged or arising, unless otherwise prohibited by law. Nothing in this Agreement or the Transaction Agreements (as defined in the Purchase Agreement) shall restrict the Investors’ freedom to operate any of its affiliates (including any such affiliate that is a potential competitor of the Company).

6.16 Further Assurances. At any time or from time to time after the date hereof, the parties agree to cooperate with each other, and at the request of any other party, to execute and deliver any further instruments or documents and to take all such further action as the other party may reasonably request in order to evidence or effectuate the consummation of the transactions contemplated hereby and to otherwise carry out the intent of the parties hereunder.

[Remainder of Page Intentionally Left Blank]

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IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

CYTEIR THERAPEUTICS, INC.
By:	/s/ Markus Renschler
Name:	Markus Renschler
Title:	President & Chief Executive Officer

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTORS:

RA CAPITAL HEALTHCARE FUND, L.P.

By: RA Capital Healthcare Fund GP, LLC

Its General Partner

By:	/s/ Rajeev Shah
Name:	Rajeev Shah
Title:	Manager

Address:	RA Capital Management, L.P.
	200 Berkeley Street, 18th Floor
	Boston, MA 02116
	Attn: General Counsel
RA CAPITAL NEXUS FUND II, L.P.
By:	RA Capital Nexus Fund II GP, LLC
Its:	General Partner

By:	/s/ Rajeev Shah
Name:	Rajeev Shah
Title:	Manager

Address:	RA Capital Management, L.P.
	200 Berkeley Street, 18th Floor
	Boston, MA 02116
	Attn: General Counsel

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

		INVESTORS:
JANUS HENDERSON GLOBAL LIFE SCIENCES FUND		JANUS HENDERSON BIOTECH INNOVATION MASTER FUND LIMITED
By: Janus Capital Management LLC, its investment advisor		By: Janus Capital Management LLC, its investment advisor
By:	/s/ Andrew Acker	By:	/s/ Andrew Acker
Name:	Andrew Acker	Name:	Andrew Acker
Title:	Authorized Signatory	Title:	Authorized Signatory
Address:	c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker Attn: Angela Morton	Address:	c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker Attn: Angela Morton
JANUS HENDERSON CAPITAL FUNDS PLC ON BEHALF OF ITS SERIES JANUS HENDERSON GLOBAL LIFE SCIENCES FUND		JANUS HENDERSON HORIZON FUND - BIOTECHNOLOGY FUND
By: Janus Capital Management LLC, its investment advisor		By: Janus Capital Management LLC, its investment advisor
By:	/s/ Andrew Acker	By:	/s/ Andrew Acker
Name:	Andrew Acker	Name:	Andrew Acker
Title:	Authorized Signatory	Title:	Authorized Signatory
Address:	c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker Attn: Angela Morton	Address:	c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker Attn: Angela Morton

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTORS:
667, L.P.
BY:	BAKER BROS. ADVISORS LP, management company and investment adviser to 667, L.P., pursuant to authority granted to it by Baker Biotech Capital, L.P., general partner to 667, L.P., and not as the general partner.
By:	/s/ Scott Lessing
	Name: Scott Lessing
	Title: President
	Address:  Baker Bros. Advisors LP 860 Washington St., 3rd Floor
	New York, N.Y. 10014
BAKER BROTHERS LIFE SCIENCES, L.P.
By:	BAKER BROS. ADVISORS LP,
management company and investment adviser to Baker Brothers Life Sciences, L.P., pursuant to authority granted to it by Baker Brothers Life Sciences Capital, L.P., general partner to Baker Brothers Life Sciences, L.P., and not as the general partner.
	/s/ Scott Lessing
	Name: Scott Lessing
	Title: President
	Address:  Baker Bros. Advisors LP 860 Washington St., 3rd Floor
	New York, N.Y. 10014

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

ALLY BRIDGE MEDALPHA MASTER FUND L.P.

By: Ally Bridge Group (NY) LLC, its manager

By:	/s/ Anna Yaeger
Name:	Anna Yaeger
Title:	Portfolio Manager and President

Address:	c/o Ally Bridge Group (NY) LLC
	430 Park Avenue, 12th Floor
	New York, NY 10022

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:
ACUTA CAPITAL FUND, LP
By: Acuta Capital Partners, LLC
Its: General Partner
By:	/s/ Scott R. Smith
Name:	Scott R. Smith
Title:	Chief Operating Officer

Address:	1301 Shoreway Road, Suite 350, Belmont, CA 94002
ACUTA OPPORTUNITY FUND, LP
By: Acuta Capital Partners, LLC
Its: General Partner

By:	/s/ Scott R. Smith
Name:	Scott R. Smith
Title:	Chief Operating Officer

Address: 1301 Shoreway Road, Suite 350, Belmont, CA 94002

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTORS:

AVIDITY MASTER FUND LP

By: Avidity Capital Partners Fund (GP) LP,

its General Partner

By:	/s/ Michael Gregory
Name:	Michael Gregory
Title:	Director

Address:	2828 N. Harwood St., Suite 1220
	Dallas, TX 75201
AVIDITY CAPITAL FUND II LP
By: Avidity Capital Partners Fund (GP) LP,
its General Partner

By:	/s/ Michael Gregory
Name:	Michael Gregory
Title:	Director

Address:	2828 N. Harwood St., Suite 1220
	Dallas, TX 75201

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:
STRENGTH ALLIANCE LIMITED
c/o Ample Plus Fund Limited Partnership
By:	/s/ Chunshan Tang
Name:	Chunshan Tang
Title:	Authorized Signatory

Address: One Broadway, 9^th Floor Cambridge, MA 02142

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:
CAAS OPPORTUNITY LLC
By:	/s/ Semi Gogliormella
Name:	Semi Gogliormella
Title:	COO

Address:	800 Third Avenue, 26th floor
	New York, New York 10022

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:
NOVO HOLDINGS A/S
By:	/s/ Scott Beardsley
Name:	Scott Beardsley
	under specific power of attorney
Title:	Managing Partner

Address:	Novo Holdings A/S
	Tuborg Havnevej 19
	DK 2900 Hellerup
	Denmark

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:
DROIA INVEST II SCSP
By: DF II GP Sàrl, Its: General Partner
By:	/s/ Janwillem Naesens
Name:	Janwillem Naesens
	(representing Wepaven BV)
Title:	Manager

Address:	Boulevard Joseph II 28
	L-1840 Luxembourg

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTORS:

VENROCK ASSOCIATES VII, L.P.

By:	Venrock Management VII, LLC
Its:	General Partner

By:	/s/ David L. Stepp
Name:	David L. Stepp
Title:	Authorized Signatory

Address:	3340 Hillview Avenue
	Palo Alto, CA 94304

VENROCK PARTNERS VII, L.P.
By:	Venrock Management VII, LLC
Its:	General Partner

By:	/s/ David L. Stepp
Name:	David L. Stepp
Title:	Authorized Signatory

Address:	3340 Hillview Avenue
	Palo Alto, CA 94304

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

OSAGE UNIVERSITY PARTNERS II, LP

By:	Osage University GP II, LLC
Its:	General Partner

By:	/s/ William T. Harrington
Name:	William Harrington
Title:	Managing Member

Address:	50 Monument Rd., Suite 201
	Bala Cynwyd, PA 19004

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTORS:

LIGHTSTONE VENTURES II, L.P.

By:	/s/ Jean George
Name:	Jean George
Title:	General Partner

Address:	500 Boylston Street, Suite 1380
	Boston, MA 02116
LIGHTSTONE VENTURES II (A), L.P.

By:	/s/ Jean George
Name:	Jean George
Title:	General Partner

Address:	500 Boylston Street, Suite 1380
	Boston, MA 02116

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

CELGENE CORPORATION

By:	/s/ Daniel O’Connell
Name:	Daniel O’Connell
Title:	Authorized Signatory

Address:	86 Morris Avenue
	Summit, NJ 07901

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

THE JACKSON LABORATORY

By: /s/ Douglas Abbott

Name:	Douglas Abbott
Title:	CFO
Address:	c/o Mary McWade
	Merrill Lynch
	Private Banking & Investment Group
	100 Federal Street, 17th Floor
	MA5-100-17-7
	Boston, MA 02110

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

Z INVESTMENTS, LLC

By: /s/ Joseph S Zakrzewski

Name:	Joseph S Zakrzewski
Title:	Managing Director
Address:	509 Waterview Place
	New Hope, PA 19838

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

IN WITNESS WHEREOF, the parties have executed this Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

INVESTOR:

Signature: /s/ Timothy Romberger

Name:	Timothy Romberger
Address:	60 Glendale Ave
	Hinsdale, IL 60521

SIGNATURE PAGE TO SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

SCHEDULE A

SERIES A INVESTORS

Name and Address	Number of Shares of Series A Preferred Stock Held
The David and Barbara Roux Trust udt 8/11/99 9323 Saint Brides Lane Upperville, VA 20184		2,000,000
Celgene Corporation 86 Morris Avenue Summit, NJ 07901		2,000,000
Anthony Evnin 364 East Middle Patent Road Greenwich, CT 06831		250,000
Weslie Janeway 8 East 80th Street New York, NY 10075		250,000
Milch Investment Holdings, LLC 12 Nightingale Ct. Manhasset, NY 11030		250,000
David Shaw c/o Maly McWade Menill Lynch Private Banking & Investment Group 100 Federal Street 17th Floor MA5-100-17-7 Boston, MA 02110		250,000
Ehmock Energy Holdings c/o Elmrock 150 East 58th Street 27th Floor New York, NY 10155		250,000
Mills Family 1 LLC 175 Blossom Street Boston, MA 02114		75,000
K&BM LP 175 Blossom Street Boston, MA 02114		75,000

Krishnan-Shah Family Partners, LP 27241 Altamont Road Los Altos Hills, CA 94022	100,000
Geis-Hides Consulting 808 N. Greenview Ave, Unit 3A Chicago, IL 60642	83,403
Timothy Romberger 60 Glendale Ave Hinsdale, IL 60521	69,503
Robert Barbanell 35 Sutton Place New York, NY 10022	32,545
William Rudolf 211 Central Park West New York, NY 10024	32,545
Farzad Nazem & Noosheen Hashemi Living Trust Dated 07/10/95 1259 El Camino Real, #88 Menlo Park, CA	100,000

SCHEDULE A (cont.)

SERIES B INVESTORS

Name and Address	Number of Shares of Series B         Preferred Stock Held
Venrock Associates VII, L.P. 3340 Hillview Avenue Palo Alto, CA 94304	9,235,000
Venrock Partners VII, L.P. 3340 Hillview Avenue Palo Alto, CA 94304	765,000
DROIA Invest II SCSP Boulevard Joseph II 28 L-1840 Luxembourg	10,000,000
Lightstone Ventures II, L.P. 500 Boylston Street, Suite 1380 Boston, MA 02116	7,115,217
Lightstone Ventures II (A), L.P. 500 Boylston Street, Suite 1380 Boston, MA 02116	384,783
Osage University Partners II, LP 50 Monument Rd., Suite 201 Bala Cynwyd, PA 19004	7,592,987
Celgene Corporation 86 Morris Avenue Summit, NJ 07901	3,957,013
Anthony Evnin 364 East Middle Patent Road Greenwich, CT 06831	250,000
Weslie Janeway 8 East 80th Street New York, NY 10075	500,000
Milch Investment Holdings, LLC 12 Nightingale Ct. Manhasset, NY 11030	500,000

Elmrock Energy Holdings, LLC c/o Elmrock 150 East 58th Street, 27th Floor New York, NY 10155	500,000
Timothy Romberger 60 Glendale Ave Hinsdale, IL 60521	200,000
Novo Holdings A/S Tuborg Havnevej 19 DK-2900 Hellerup Denmark Attn: Heather Ludvigsen Email: hlud@novo.dk with a copy (which shall not constitute notice) to: Novo Ventures (US), Inc. 501 2nd Street, Suite 300 San Francisco, CA 94107 United States Attention: Junie Lim and Karen Hong Email: jeql@novo.dk and KHO@novo.com	14,000,000
Z Investments, LLC 509 Waterview Place New Hope, PA 18938	200,000

SCHEDULE A (cont.)

SERIES C INVESTORS

Name and Address	Number of Shares of Series C         Preferred Stock Held
RA Capital Healthcare Fund, L.P. c/o RA Capital Management, L.P. 200 Berkeley Street 18th Floor Boston, MA 02116 Attn: General Counsel	5,786,611
RA Capital NEXUS Fund II, L.P. c/o RA Capital Management, L.P. 200 Berkeley Street 18th Floor Boston, MA 02116 Attn: General Counsel	1,021,167
Janus Henderson Global Life Sciences Fund c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker (andy.acker@janushenderson.com) Attn: Angela Morton (angela.morton@janushenderson.com)	1,873,655
Janus Henderson Biotech Innovation Master Fund Limited c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker (andy.acker@janushenderson.com) Attn: Angela Morton (angela.morton@janushenderson.com)	621,760
Janus Henderson Capital Funds plc on behalf of its series Janus Henderson Global Life Sciences Fund c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker (andy.acker@janushenderson.com) Attn: Angela Morton (angela.morton@janushenderson.com)	1,521,076

Name and Address	Number of Shares of Series C         Preferred Stock Held
Janus Henderson Horizon Fund – Biotechnology Fund c/o Janus Capital Management LLC 151 Detroit Street Denver, CO 80206 Attn: Andy Acker (andy.acker@janushenderson.com) Attn: Angela Morton (angela.morton@janushenderson.com)	68,176
667, L.P. c/o Baker Bros. Advisors L.P. 860 Washington Street 3rd Floor New York, NY 10014	120,790
Baker Brothers Life Sciences, L.P. c/o Baker Bros. Advisors L.P. 860 Washington Street 3rd Floor New York, NY 10014	1,513,076
Ally Bridge MedAlpha Master Fund L.P. 430 Park Avenue 12th Floor New York, NY 10022	1,089,244
Acuta Capital Fund, LP 1301 Shoreway Road, Suite 350 Belmont, CA 94002 Attn: Scott Smith, Chief Operating Officer Email: ssmith@acutacapital.com	904,073
Acuta Opportunity Fund, LP 1301 Shoreway Road, Suite 350 Belmont, CA 94002 Attn: Scott Smith, Chief Operating Officer Email: ssmith@acutacapital.com	185,171
Avidity Master Fund LP 2828 N. Harwood St., Suite 1220 Dallas, TX 75201 Michael.Gregory@aviditypartners.com	867,859

Name and Address	Number of Shares of Series C         Preferred Stock Held
Avidity Capital Fund II LP 2828 N. Harwood St., Suite 1220 Dallas, TX 75201 Michael.Gregory@aviditypartners.com	221,385
Strength Alliance Limited One Broadway, 9th Floor Cambridge, MA 02142 luke@ampleplus.fund and andrew.aherrera@ampleplus.fund	272,311
CaaS Opportunity LLC 800 Third Avenue, 26th floor New York, New York 10022 c/o Semi Gogliormella Email: semi.gogliormella@caascap.com	272,311
Novo Holdings A/S Tuborg Havnevej 19 DK-2900 Hellerup Denmark Attn: Heather Ludvigsen Email: hlud@novo.dk with a copy (which shall not constitute notice) to: Novo Ventures (US), Inc. 501 2nd Street, Suite 300 San Francisco, CA 94107 United States Attention: Junie Lim and Karen Hong Email: jeql@novo.dk and KHO@novo.com	1,553,116
DROIA Invest II SCSP Boulevard Joseph II 28 L-1840 Luxembourg	1,109,368
Venrock Associates VII, L.P. 3340 Hillview Avenue Palo Alto, CA 94304	1,024,501
Venrock Partners VII, L.P. 3340 Hillview Avenue Palo Alto, CA 94304	84,867

Name and Address	Number of Shares of Series C         Preferred Stock Held
Osage University Partners II, LP 50 Monument Rd., Suite 201 Bala Cynwyd, PA 19004	842,342
Lightstone Ventures II, L.P. 500 Boylston Street, Suite 1380 Boston, MA 02116	786,265
Lightstone Ventures II (A), L.P. 500 Boylston Street, Suite 1380 Boston, MA 02116	45,761

SCHEDULE A (cont.)

INVESTORS

Name and Address	Number of Shares of Common Stock Held
The Jackson Laboratory c/o Mary McWade Merrill Lynch Private Banking & Investment Group 100 Federal Street, 17th Floor MA5-100-17-7 Boston, MA 02110	1,339,750

SCHEDULE B

KEY INVESTORS

Key Investor Name

Venrock Associates VII, L.P.

Venrock Partners VII, L.P.

Celgene Corporation*

Droia Invest II SCSP

Lightstone Ventures II, L.P.

Lightstone Ventures II (A), L.P.

Osage University Partners II, LP

Novo Holdings A/S

RA Capital Healthcare Fund, L.P.

RA Capital NEXUS Fund II, L.P.

* Celgene Corporation will constitute a “Key Investor” for purposes of the Company’s Certificate of Incorporation for any future financing only to the extent that Celgene Corporation owns 15% or less of the outstanding shares of capital stock of the Company (on an as-converted basis, but, for clarity, includes all shares of the Company’s common and preferred stock and excludes outstanding but unexercised stock options and shares issuable upon conversion of any other convertible securities). For the avoidance of doubt, Article Fourth, Section B.5A.1 of the Company’s Certificate of Incorporation will apply to Celgene Corporation up until Celgene Corporation’s ownership is 15% of the outstanding shares of capital stock of the Company (on an as-converted basis, but, for clarity, includes all shares of the Company’s common and preferred stock and excludes outstanding but unexercised stock options and shares issuable upon conversion of any other convertible securities), even if Celgene Corporation only invests a portion of its pro rata amount in a future purchase.

EX-10.1

Exhibit 10.1

CYTEIR THERAPEUTICS, INC.

LEDGEMONT RESEARCH CENTER

LEXINGTON, MA

TABLE OF CONTENTS

ARTICLE 1 : BASIC TERMS		1
ARTICLE 2 : PREMISES AND APPURTENANT RIGHTS		3
2.01.	Lease of Premises; Appurtenant Rights	3
2.02.	Right of First Offer on Certain Additional Space	5
2.03.	Roof License	6
2.04.	Emergency Generator Capacity	9
ARTICLE 3 : LEASE TERM		9
3.01.	Lease Term	9
3.02.	Hold Over	9
3.03.	Right to Extend	10
ARTICLE 4 : RENT		11
4.01.	Base Rent	11
4.02.	Additional Rent	11
4.03.	Late Charge	13
4.04.	Interest	13
4.05.	Method of Payment	13
4.06.	Tenant’s Pro Rata Share	14
ARTICLE 5 : TAXES		15
5.01.	Taxes	15
5.02.	Definition of “Taxes”	15
5.03.	Personal Property Taxes	15
ARTICLE 6 : UTILITIES AND LANDLORD SERVICES		15
6.01.	Utility Services	15
6.02.	Landlord Services	16
6.03.	Excess Usage by Tenant	17
ARTICLE 7 : INSURANCE		17
7.01.	Coverages	17
7.02.	Avoid Action Increasing Rates	19
7.03.	Waiver of Subrogation	19
7.04.	Landlord’s Insurance	20
ARTICLE 8 : OPERATING EXPENSES		20
8.01.	Operating Expenses	20
ARTICLE 9 : USE OF PREMISES		21

i

9.01.	Permitted Uses	21
9.02.	Indemnification	21
9.03.	Compliance With Legal Requirements	22
9.04.	Environmental Substances	23
9.05.	Signs and Auctions	25
9.06.	Landlord’s Access	25
ARTICLE 10 : CONDITION AND MAINTENANCE OF PREMISES AND PROPERTY		25
10.01.	Existing Conditions	25
10.02.	Exemption and Limitation of Landlord’s Liability	25
10.03.	Landlord’s Obligations	26
10.04.	Tenant’s Obligations	27
10.05.	Tenant Work	28
10.06.	Condition upon Termination	31
10.07.	Decommissioning of the Premises	32
ARTICLE 11 : INITIAL TENANT IMPROVEMENTS		33
ARTICLE 12 : DAMAGE OR DESTRUCTION; CONDEMNATION		36
12.01.	Damage or Destruction of Premises	36
12.02.	Eminent Domain	37
ARTICLE 13 : ASSIGNMENT AND SUBLETTING		38
13.01.	Landlord’s Consent Required	38
13.02.	Terms	39
13.03.	Right of Termination or Recapture	40
13.04.	Procedures	40
13.05.	Excess Rents	41
13.06.	No Release	41
13.07.	Certain Additional Rights	42
ARTICLE 14 : EVENTS OF DEFAULT AND REMEDIES		42
14.01.	Events of Default	42
14.02.	Remedies for Default	44
ARTICLE 15 : LETTER OF CREDIT		46
ARTICLE 16 : PROTECTION OF LENDERS		48
16.01.	Subordination and Superiority of Lease	48
16.02.	Rent Assignment	49
16.03.	Other Instruments	49

-ii-

16.04.	Estoppel Certificates	49
16.05.	Tenant’s Financial Condition	50
ARTICLE 17 : MISCELLANEOUS PROVISIONS		50
17.01.	Landlord’s Consent Fees	50
17.02.	Notice of Landlord’s Default	50
17.03.	Quiet Enjoyment	50
17.04.	Interpretation	51
17.05.	Notices	51
17.06.	No Recordation	51
17.07.	Security Measures	51
17.08.	Corporate Authority	51
17.09.	Intentionally Omitted	52
17.10.	Joint and Several Liability; Right to Lease	52
17.11.	Force Majeure	52
17.12.	Limitation of Warranties	52
17.13.	No Other Brokers	53
17.14.	Applicable Law and Construction	53
17.15.	Construction on the Property or Adjacent Property	54
17.16.	Vacancy at End of Term	55
17.17.	Confidentiality	55
17.18.	OFAC CERTIFICATION AND INDEMNITY	55
17.19.	WAIVER OF JURY TRIAL	56

-iii-

ARTICLE 1: BASIC TERMS

The following terms used in this Lease shall have the meanings set forth below.

Date of Lease:	August 08, 2018
Landlord:	128 Spring Street Lexington, LLC, a Delaware limited liability company
Tenant:	CYTEIR THERAPEUTICS, INC., a Delaware corporation
Building and Property:	The building complex known as Ledgemont Technology Center and consisting of the “A Building.” “B Building, “ “C Building,” “D Building.” “E Building” and the parking garage and other appurtenances thereto located at 99 Hayden Avenue, Lexington, Massachusetts (the “Building” and such parcel of land hereinafter being collectively referred to as the “Property”).
Premises:	Portions of the Building consisting of approximately 7, 442 rentable square feet located on the 500 Level of Building A, as described in Exhibit A.
Initial Term:	Five (5) Lease Years (defined below) commencing on the Term Commencement Date (defined below).
Extension Term:	One (1) additional term of three (3) Lease Years.
Lease Year:	A period of twelve (12) consecutive months, commencing on the Term Commencement Date and each successive twelve (12) month period during the Term, except that if the Term Commencement Date shall occur on a date other than the first day of a month, then the first Lease Year shall include the period of the Term Commencement Date to the first day of the following month and twelve (12) calendar months thereafter.
Anticipated Term Commencement Date:	November 1, 2018.
Term Commencement Date:	The Substantial Completion Date, as defined in Section 11.4 below.
Permitted Uses:	General office, research and laboratory use(s) only and lawful ancillary uses relating thereto.
Tenant’s Pro Rata Share:	3.97% subject to Section 4.06.

Brokers:	JLL (Landlord) and Newmark Knight Frank (Tenant) by separate letter agreement between Landlord and Brokers.
Landlord’s Managing Agent:	Related Beal, LLC
Letter of Credit Amount:	$143, 258.50, subject to reduction as provided in Article 15 below.
Parking:	As set forth in Section 2.01(d) of the Lease.
Base Rent:	Initial Term:

Lease Year	Base Rent	Base Rent Monthly Installment
1	$286, 517.00	$23, 876.42
2	$295, 149.72	$24, 595.81
3	$304, 005.70	$25, 333.81
4	$313, 159.36	$26, 096.61
5	$322, 536.28	$26, 878.02
Extension Term:	As provided in Section 3.03(b).

Additional Rent:	All amounts payable by Tenant under this Lease other than Base Rent, including, without limitation, Tenant’s Pro Rata Share of Taxes (Article 5); Utilities (Article 6); Insurance premiums (Article 7); and Operating Expenses (Article 8) (See Section 4.02). Tenant’s Pro Rata Share is defined in Section 4.06 hereof.
Original Address of Landlord for Notices:	c/o Related Beal 177 Milk Street Boston, Massachusetts 02109 Attention: Lease Coordinator with copies to: c/o Related Beal 177 Milk Street Boston, Massachusetts 02109 Attention: General Counsel             - and - Sherin and Lodgen LLP 101 Federal Street Boston, Massachusetts 02110 Attention: Robert M. Camey, Esquire

-2-

Original Address of Tenant for Notices:	Before Term Commencement Date: 763E Concord Avenue Cambridge, Massachusetts 02138 Attention: Markus Renschler, MD
	After Term Commencement Date: Ledgemont Research Center 99 Hayden Avenue Lexington Massachusetts 02421 Attention: Markus Renschler, MD
Tenant Improvement Allowance:	$50, 00 per rentable square foot of the Premises, and as further provided in Article 11
Additional Improvement Allowance:	Up to a maximum of $20.00 per square foot of Rentable Area in the, as provided in Section 11.09.
Initial Tenant Improvements:	To be constructed by Landlord as set forth in Article 11.
Exhibits:	Exhibit A:  Floor Plan of the Premises Exhibit B:   Rules and Regulations Exhibit C:   Rules and Regulations for Tenant Work Exhibit D:  Tenant Work Insurance Schedule Exhibit E:   Form of Term Commencement Date Agreement Exhibit F:   Construction Documents Exhibit G:  Environmental Substances Exhibit H:  Plans and Specifications for Initial Tenant Improvements Exhibit I:  Plan Showing Additional Space Exhibit J:  Form of Letter of Credit

ARTICLE 2: PREMISES AND APPURTENANT RIGHTS

2.01.    Lease of Premises; Appurtenant Rights. Landlord hereby leases the Premises to Tenant, and Tenant hereby leases the Premises from Landlord, for the Term, subject to all matters of record and matters referred to below. Subject to Landlord’s rules and regulations attached hereto as Exhibit B and such other reasonable rules and regulations as Landlord may from time to time adopt and of which Tenant is given notice (collectively, “Landlord’s Rules”) and to Force Majeure (as hereinafter defined), Tenant shall have access to the Premises twenty-four (24) hours a day, seven (7) days a week. Landlord shall enforce the rules and regulations in a uniform manner and in the event of any express conflict between the terms of this Lease and the Landlord’s Rules, the terms of this Lease shall govern.

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(a)    Exclusions. The Premises exclude common areas and facilities of the Property, including, without limitation, exterior faces of exterior walls, the common stairways and stairwells (subject to Tenant’s rights to use the stairways for access between portions of the Premises pursuant to Section 2.01(b)), entranceways and the main lobby, elevators and elevator wells, fan rooms, electric and telephone closets, janitor closets, freight elevator vestibules, and pipes, ducts, conduits, wires and appurtenant fixtures serving other parts of the Property (exclusively or in common) and other common areas and facilities from time to time designated as such by Landlord. If the Premises include less than the entire rentable area of any floor, then the Premises also exclude the common corridors, elevator lobby and toilets located on such floor.

(b)    Appurtenant Rights. Tenant shall have, as appurtenant to the Premises, the nonexclusive right to use in common with others (subject to Landlord’s Rules and Force Majeure) the common areas and facilities of the Property necessary for Tenant’s use and occupancy of the Premises, including, without limitation, the loading dock servicing the tenants and occupants of the Building, but excluding the entrance to A Building. Subject to Landlord’s Rules and to Force Majeure, Tenant shall have access to the seating area of the common cafe in the Building twenty-four (24) hours a day, seven (7) days a week.

(c)    Reservations. In addition to other rights reserved herein or by law, Landlord reserves the right from time to time, provided that Landlord shall use commercially reasonable efforts to avoid unreasonable (except in emergency) interference of Tenant’s use of the Premises: (i) to make additions to or reconstructions of the Building and to install, use, maintain, repair, replace and relocate for service to the Premises and other parts of the Building, or either, pipes, ducts, conduits, wires and appurtenant fixtures, wherever located in the Premises, the Building, or elsewhere in the Property; (ii) to alter, eliminate or relocate any other common area or facility, including the drives, lobbies and entrances; and (iii) to grant easements and other rights with respect to the Property; provided, however, that Landlord’s exercise of any of the foregoing rights shall not result in a decrease of the square footage of the Premises in any material respect. Installations, replacements and relocations within the Premises referred to in clause (i) shall be located as far as practicable in the core areas of the Building, above ceiling surfaces, below floor surfaces or within perimeter walls of the Premises. The Building may be subdivided or combined into separate or unified lots, submitted to or removed from a condominium regime or divided or combined into separate leasehold lots by ground leases to facilitate financing, ownership or operation of all or portions of the Property and Building, provided that Tenant’s rights and obligations under this Lease shall not be affected in any material respect Tenant agrees to enter into any instruments reasonably requested by Landlord in connection with the foregoing so long as the same are not inconsistent with the rights of Tenant under this Lease and are otherwise reasonably acceptable to Tenant.

(d)    Parking.

(i)    Commencing on the Term Commencement Date, Tenant shall have, at no additional cost to Tenant, the appurtenant right to use up 2.5 unreserved parking spaces for standard size automobiles and small utility vehicles per 1, 000 rentable square feet of the Premises. The parking spaces shall be used by Tenant and Tenant’s employees and business invitees and may be located on or about the Property and/or within the parking garage, and the location of said parking spaces, and the layout and location of the parking facilities, are subject to change from time to time. Tenant’s right to use such parking spaces shall be non-exclusive. Tenant shall have access to the parking area(s) of the Building twenty-four (24) hours a day, seven (7) days a week.

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(ii)    None of Tenant’s parking rights hereunder shall be assigned or sublicensed except in connection with a Transfer permitted under Article 13. Landlord shall have the right to make such parking available pursuant to a pass system or on any other reasonable basis determined by Landlord, and such parking rights shall be subject to Landlord’s reasonable rules and regulations of which Tenant is provided written notice, from time to time, and the right of Landlord to limit the number of parking spaces available to Tenant, its employees and invitees, where the use of the same exceeds the above-stated ratio. Tenant acknowledges that Landlord has informed Tenant that Landlord intends to allocate in its tenant leases more than the actual parking spaces servicing the Property. It is further acknowledged and agreed that as a consequence of such over-allocation of parking spaces, there may occasionally occur instances in which the number of parking spaces actually available to Tenant shall be less than the parking spaces to which Tenant is permitted to use under this Lease. Landlord shall incur no liability to Tenant as a consequence of such over-allocation of parking spaces. Landlord shall have the right to alter the parking areas or their operation from time to time, and to temporarily close portions thereof for maintenance as necessary. Tenant’s parking privileges constitute a license only, and no bailment is intended or shall be created. Neither Landlord nor any parking operator of the parking areas will have any responsibility for loss or damage due to fire or theft or otherwise to any automobile parked in the parking areas or to any personal property therein.

2.02.    Right of First Offer on Certain Additional Space.

(a)    Provided this Lease is then in full force and effect and Tenant is not then in default hereunder (beyond any applicable notice and cure periods), in the event that during the Initial Term any of the Additional Space (defined below) becomes available (meaning that no other tenant or occupant is occupying the Additional Space, has entered into occupancy of the Additional Space or any portion thereof, or has executed a lease or occupancy agreement or a written commitment or letter of intent to lease or occupy same), Tenant shall have the one-time right of first offer to lease such Additional Space subject to and in accordance with the terms and conditions set forth in this Section 2.02. The Additional Space shall be comprised of the contiguous space in the “A Building” shown on Exhibit I attached hereto (the “Additional Space”). If at any time from and after the Term Commencement Date, any of the Additional Space shall become available for occupancy, Landlord shall notify Tenant thereof in writing (“Landlord’s Additional Space Notice”), which notice shall include the anticipated estimated date upon which such Additional Space shall become available for occupancy by Tenant, the proposed term for the Additional Space and the economic terms upon which Landlord would be willing to lease the Additional Space to Tenant. Tenant shall have the right to lease all such Additional Space described in Landlord’s Additional Space Notice only by giving written notice to Landlord within ten (10) days after Tenant receives Landlord’s Additional Space Notice, time being of the essence For the purposes hereof, space shall be deemed “available for occupancy” when any lease or occupancy agreement (including extension periods) has expired or is due to expire within not less than six (6) months, or Landlord has elected not to renew or otherwise extend the lease of the present tenant, and any prior options, rights or rights to lease with respect to such Additional Space have expired or been waived and Landlord is free to lease such space to third parties without restriction,

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(b)    If Tenant so elects to lease the Additional Space, the Additional Space shall be leased to Tenant upon the same terms and conditions contained in this Lease, except for Base Rent, which shall be the Market Rent as initially set forth in Landlord’s Additional Space Notice and determined in accordance with Sections 3.03(c), (d) and (e) below if Tenant disputes same (made applicable hereto by such changes and modifications as are required given the application hereof, mutatis mutandis) and the Additional Space shall be and become part of the Premises hereunder upon the delivery of the Additional Space to Tenant (the “Additional Space Commencement Date”). It is understood and agreed that the Additional Space shall be leased by Tenant in its then “as is” condition, without warranty or representation by Landlord, and that Landlord shall have no obligation to complete any work to prepare the Additional Space for Tenant’s occupancy. Following such election by Tenant, and effective as of the Additional Space Commencement Date and for the balance of the Term and any extension thereof: (a) the “Premises”, as used in this Lease, shall also include the Additional Space; (b) Tenant’s Pro Rata Share of Operating Expenses and Tenant’s Pro Rata Share of Taxes shall be increased to include the rentable square footage of the Additional Space; and (c) the Base Rent shall equal the sum of the Base Rent provided for in this Lease for the original Premises plus the Base Rent for the Additional Space as stated in Landlord’s First Offer Notice. The foregoing terms and provisions shall be self-operative, but to confirm the foregoing, Landlord shall prepare a mutually agreed upon amendment to this Lease reflecting the foregoing terms, which shall be signed by Landlord and Tenant within ten (10) days of submission.

(c)    If Tenant fails to timely exercise any of its rights hereunder, or if Landlord and Tenant are unable to agree upon an amendment to reflect the lease of the Additional Space, the right(s) granted hereunder as to the Additional Space shall expire, terminate and be of no further force and effect waived for all purposes, and Landlord may lease all or any portion of the Additional Space to any party and upon any terms free of any rights of Tenant. Tenant, following such waiver and within seven (7) days of Landlord’s request therefor, shall execute and deliver to Landlord a certification, in recordable form, confirming the waiver of such right, and Tenant’s failure to so execute and deliver such certification shall (without limiting Landlord’s remedies on account thereof) entitle Landlord to execute and deliver to any third party, and record, an affidavit confirming the waiver, which affidavit shall be binding on Tenant and may be conclusively relied on by third parties.

(d)    Tenant understands that its rights under this Section are and shall be subject and subordinate to any options to lease or any rights of first negotiation, first offer or first refusal to lease granted to other tenants of the Building prior to the date of execution and delivery of this Lease.

2.03.    Roof License.

(a)    Tenant shall have the non-exclusive license, at no additional cost, to install, operate and maintain, all in good order and repair, an antenna or dish (“Antenna”) and supplemental HVAC unit (“Tenant’s HVAC Unit”) on a portion or portions of the roof of the Building (“Roof”) in compliance with all of the terms and conditions of this Lease, including, but not limited to, Section 10.05 and Exhibit C. Tenant acknowledges and agrees that the right granted to Tenant hereunder is a non-exclusive license and is not a lease or an appurtenant right to the Premises and, further, that Tenant’s liabilities and obligations under this Lease are not contingent or conditioned upon its ability to use the Antenna and Tenant shall continue to be obligated to perform all of its obligations under the Lease if Tenant is unable to use the Antenna. Tenant shall only use the Antenna to transmit and receive data transmissions for Tenant’s use in the Premises. No person or entity other than Tenant (or a Permitted Transferee, subtenant, successor or assign) shall have the right to use or receive transmissions from the Antenna.

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(b)    The Antenna and Tenant’s HVAC Unit shall be of a size and location approved by Landlord, which approval shall not be unreasonably withheld, conditioned or delayed as to nonstructural aspects thereof (nonstructural aspects being those that do not adversely affect the Building’s structure, roof, exterior or mechanical, electrical, plumbing, life safety or other Building systems or architectural design, character or use of the Premises or the Building), and shall be installed at a location or locations on the Roof selected by Landlord, in its sole but reasonable discretion, and Landlord shall have the right, to be exercised in good faith, to require Tenant to relocate the Antenna, but not Tenant’s HVAC Unit, from time to time, at Tenant’s sole cost and expense. Landlord makes no representation or warranty to Tenant that the Roof will be satisfactory to Tenant or will permit Tenant to receive the transmissions it desires to receive. Prior to installing, removing or replacing either the Antenna or Tenant’s HVAC Unit, Tenant shall submit to Landlord plans and specifications for the installation of the Antenna and/or Tenant’s HVAC Unit, as the case may be, prepared by a licensed engineer reasonably satisfactory to Landlord (the “Plans”). The Plans shall be reasonably satisfactory to Landlord, and shall show the location of the installations of the Antenna and/or Tenant’s HVAC Unit and all related equipment and components on the Roof, the location and type of all piping, conduit, wiring, cabling, the manner in which the Antenna and/or Tenant’s HVAC Unit will be placed on and fastened to the Roof, number, type, size and sealing of any Roof penetrations, and any other information requested by Landlord, in Landlord’s good faith discretion. Landlord shall have the right to require that the Antenna and/or Tenant’s HVAC Unit not be visible from any location on the ground and/or that the all such equipment be screened in a manner satisfactory to Landlord, in Landlords good faith discretion. Landlord shall have the right to employ an engineer or other consultant to review the Plans and the reasonable, actual cost of such engineer or consultant shall be paid by Tenant to Landlord within thirty (30) days after request therefor. After Landlord has approved the Plans and prior to installing the Antenna and/or Tenant’s HVAC Unit and any related equipment, wiring, conduit, piping, or cabling, Tenant shall obtain and provide to Landlord: (a) all required governmental and quasi-governmental permits, licenses, special zoning variances and authorizations, as required by applicable local, state or federal laws, regulations or ordinances, all of which Tenant shall obtain at its own cost and expense; and (b) a policy or certificate of insurance evidencing such insurance coverage as may be reasonably required by Landlord. Any alteration or modification of the Antenna and/or Tenant’s HVAC Unit or any associated piping, conduit, wiring, cabling, equipment after the Plans have been approved shall require Landlord’s prior written approval, which may be given or withheld in Landlord’s good faith discretion.

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(c)    Installation and maintenance of the Antenna, Tenant’s HVAC Unit or any associated piping, conduit, wiring, cabling, equipment shall be performed solely by contractors approved by Landlord, in its reasonable discretion. Landlord’s may require Tenant to use a roofing contractor selected by Landlord to perform any work that could damage, penetrate or alter the Roof and an electrician selected by Landlord to install any associated piping, conduit, wiring, cabling, equipment on the Roof or in the Building. Landlord may require anyone going on the Roof to execute in advance a liability waiver reasonably satisfactory to Landlord. Tenant shall bear all costs and expenses incurred in connection with the installation, operation and maintenance of the Antenna and Tenant’s HVAC Unit.

(d)    Tenant acknowledges that Landlord may decide, in its good faith discretion, from time to time, to repair or replace the Roof (hereinafter “Roof Repairs”). Tenant is encouraged to design, install and maintain the Antenna and any Roof-top Equipment in a manner that allows for Landlord to conduct Roof Repairs without any removal thereof being required (e.g., using adequately framed, reinforced, sealed and elevated dunnage and/or roof framing) and Landlord shall reasonably cooperate with Tenant to accomplish this during the review and approval of any plans therefor. If Landlord elects to make Roof Repairs, Tenant shall, upon Landlord’s request, temporarily remove the Antenna so that the Roof Repairs may be completed. The cost of removing and reinstalling the Antenna shall be paid by Tenant, at Tenant’s sole cost and expense. Landlord shall not be liable to Tenant for any damages, lost profits or other costs or expenses incurred by Tenant as the result of the Roof Repairs. Maintenance, repair and replacement of the Antenna and Tenant’s HVAC Unit shall be Tenant’s sole responsibility throughout the entire Term, Tenant shall enter into a regularly scheduled (annually or semi-annually as reasonably determined by Landlord) preventive maintenance/service contract with an HVAC contractor reasonably approved by Landlord. The service contract must become effective within thirty (30) days of the Term Commencement Date, and a copy of the service contract forwarded to the Landlord upon request. At Landlord’s option, Landlord may enter into a regularly scheduled preventive maintenance/service contract with an HVAC contractor selected by Landlord for the Tenant’s HVAC Unit serving the Premises, Tenant shall reimburse Landlord upon demand, as additional rent, the cost of such contract and will make (or reimburse Landlord if Landlord elects to make) all repairs recommended by such HVAC contractor.

(e)    On the termination or expiration of the Lease, Tenant shall remove the Antenna and all associated conduit, wiring, cabling, equipment and repair any damages caused thereby, at Tenant’s sole cost and expense. If Tenant does not remove the Antenna on or before the date this Lease terminates or expires, Tenant hereby authorizes Landlord to remove and dispose of the Antenna and associated conduit, wiring, cabling, equipment, and Tenant shall promptly reimburse Landlord for the costs and expenses it incurs in removing and disposing of same and repairing any damages caused thereby. Tenant agrees that Landlord may dispose of the Antenna and any associated conduit, wiring, cabling, equipment in any manner selected by Landlord.

(f)    Tenant’s license to operate and maintain the Antenna and Tenant’s HVAC Unit shall automatically expire and terminate on the date that the term of the Lease expires or is otherwise terminated. This license to operate and maintain the Antenna shall also terminate if any of the following continue for more than three (3) days after written notice from Landlord to Tenant: (a) the Antenna is causing physical damage to the Building or the Roof, (b) the Antenna is interfering with the normal or customary transmission or receipt of transmission or receipt of signals from or to the Building, (c) the Antenna is causing Landlord to be in violation of any agreement to which Landlord is a party or (d) the Antenna is causing Landlord to be in violation any local, state or federal law, regulation or ordinance.

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(g)    Tenant represents and warrants to Landlord that neither the Antenna nor Tenant’s HVAC Unit will cause interference with (i) any existing communications equipment installed on the Building, or (ii) with the ability of office tenants/occupants of the Building or Project to receive or transmit radio, television, telephone, microwave, short-wave, long-wave or other signals of any sort presently or hereafter installed, or (iii) with any equipment, installation, wires, cabling or machinery (electronic or otherwise) at the Building or Project Should any such interference occur, Landlord shall provide Tenant with notice of such interference and Tenant shall promptly make all necessary repairs and adjustments, at Tenant’s expense, to insure cessation of interference to Landlord’s reasonable satisfaction and any costs and expenses incurred by Landlord in connection therewith shall be paid to Landlord within thirty (30) days after Tenant’s receipt of Landlord’s invoice. If interference cannot be eliminated within forty-eight (48) hours after receipt of notice from Landlord to Tenant, Tenant shall temporarily disconnect the electric power and shut down the interfering equipment, except for intermittent operation for the purpose of testing correction of such interference. In the event Tenant does not shut down such equipment as aforesaid, Landlord may do so without liability to Tenant.

2.04.    Emergency Generator Capacity. Tenant shall have the right to access to up to five (5) watts of emergency generator capacity per square foot of that portion of the Premises dedicated to laboratory space (not to exceed 18 kw in the aggregate) from the emergency generator(s) serving the Building, from time to time.

ARTICLE 3: LEASE TERM

3.01.    Lease Term. Subject to the terms and conditions of this Lease, the Initial Term of this Lease is set forth in Article 1, unless sooner terminated as provided herein. Landlord and Tenant agree to execute a Term Commencement Date Agreement substantially in the form attached hereto as Exhibit E, or as otherwise reasonably requested by Landlord confirming the actual Term Commencement Date and expiration date of the Term, once same are determined.

3.02.    Hold Over. If Tenant (or anyone claiming through Tenant) shall remain in occupancy of the Premises or any part thereof after the expiration or early termination of the Term without a written agreement therefor executed and delivered by Landlord, then without limiting Landlord’s other rights and remedies the person remaining in possession shall be deemed a tenant at sufferance, and Tenant shall thereafter pay monthly rent (pro-rated for such portion of any partial month as Tenant shall remain in possession) at a rate equal to, for the first thirty (30) days, 150% of the amount payable as monthly Base Rent for the twelve (12) month period immediately preceding such expiration or termination, and a rate equal to 200% of the same thereafter, and in each case with all Additional Rent also payable as provided in this Lease. After Landlord’s acceptance of the full amount of such rent for the first month of such holding over, the person remaining in possession shall be deemed a tenant at will at such rent and otherwise subject to all of the provisions of this Lease. Notwithstanding the foregoing, if Landlord desires to regain possession of the Premises promptly after the termination or expiration hereof and prior to acceptance of rent for any period thereafter, Landlord may, at its option, forthwith re-enter and take possession of the Premises or any part thereof without process or by any legal process in force in the state where the Property is located. In any case, Tenant shall be liable to Landlord for all damages resulting from any failure by Tenant to vacate the Premises or any portion thereof when required hereunder.

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3.03.    Right to Extend.

(a)    Extension Term. The Term of this Lease of all of the Premises may be extended for the Extension Term by unconditional written notice from Tenant to Landlord at least nine (9) (but not more than fifteen (15)) months before the end of the Initial Term, time being of the essence. If Tenant does not timely exercise this option, or if on the date of such notice or at the beginning of the Extension Term (i) a default by Tenant exists, or (ii) Tenant is not leasing one hundred percent (100%) of the Premises, or (iii) Tenant has made any Transfer under Article 13, at Landlord’s option upon written notice to Tenant, Tenant’s right to extend the Term of this Lease shall irrevocably lapse and be void and of no further force and effect, Tenant shall have no further right to extend, and this Lease shall expire at the end of the Initial Term. If Tenant fails to timely exercise its rights hereunder, then within seven (7) days of Landlord’s request therefor, Tenant shall execute and deliver to Landlord a certification, in recordable form, confirming the Tenant’s failure to exercise (or waiver of) such right, and Tenant’s failure to so execute and deliver such certification shall (without limiting Landlord’s remedies on account thereof) entitle Landlord to execute and deliver to any third party, and record, an affidavit confirming the failure or waiver, which affidavit shall be binding on Tenant and may be conclusively relied on by third parties. All references to the Term shall mean the Initial Term as it may be extended by the Extension Term. The Extension Term shall be on all the same terms and conditions except that the Base Rent for the Extension Term shall be as set forth below.

(b)    Extension Term Base Rent. Base Rent for each year of the Extension Term shall be established as the higher of (x) of the Market Rent (as defined in Section 3.03(c)) or (y) the Base Rent last in effect for the last Lease Year prior to the Extension Term. If Tenant gives Landlord timely notice of its exercise of the Extension Term option, then Landlord shall give Tenant written notice of Landlord’s determination of Market Rent for the Premises for the Extension Term prior to the expiration of the Initial Term. Within ten (10) days after Tenant receives such notice, Tenant shall notify Landlord of its agreement with or objection to Landlord’s determination of the Market Rent, whereupon in the case of Tenant’s objection, Market Rent shall be determined by arbitration conducted in the manner set forth below. If Tenant does not notify Landlord within such ten (10) day period of Tenant’s agreement with or objection to Landlord, s determination of the Market Rent, then the Market Rent for the Extension Term shall be conclusively deemed to be Landlord’s determination of the Market Rent as set forth in Landlord’s notice to Tenant.

(c)    Arbitration of Market Rent. If Tenant timely notifies Landlord of Tenant’s objection to Landlord’s determination of Market Rent under the preceding subsection with respect to the Extension Term, such notice shall also set forth a request for arbitration and Tenant’s appointment of a commercial real estate appraiser (an “Arbitrator”). Within five (5) business days thereafter, Landlord shall by notice to Tenant appoint a second Arbitrator. Each Arbitrator shall determine the Market Rent for the Extension Term within thirty (30) days after Landlord’s appointment of the second Arbitrator. On or before the expiration of such thirty (30) day period, the two Arbitrators shall confer to compare their respective determinations of the Market Rent. If the difference between the amounts so determined by the two (2) Arbitrators is less than or equal to ten percent (10%) of the lower of said amounts then the final determination of the Market Rent shall be equal to the arithmetical average of said amounts. If such difference between said amounts is greater than ten percent (10%), then the two arbitrators shall within ten (10) days thereafter to appoint a similarly qualified third Arbitrator (“Third Arbitrator”), who shall determine the Market Rent for the Extension Term within ten (10) days after his or her appointment by selecting one or the other of the amounts determined by the other two (2) Arbitrators. Each party shall bear the cost of the Arbitrator selected by such party. The cost for the Third Arbitrator, if any, shall be shared equally by Landlord and Tenant. All Arbitrators appointed hereunder shall be MAI appraisers, so-called, knowledgeable in the field of commercial real estate and experienced in the market in which the Building is located. The foregoing determination shall be conclusive, final and binding on the parties and enforceable in any court having jurisdiction over the parties.

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(d)    “Market Rent” shall be the fair market rent that willing parties would pay and receive as the Base Rent to lease similar space in the Building and similar space in similar buildings in the same geographic area, during the Extension Term and under the applicable terms and conditions of this Lease (and other relevant market factors).

(e)    Rent Continuation. For any part of the Extension Term during which the Base Rent is in dispute or has otherwise not finally been determined, Tenant shall make payment on account of Base Rent at the Market Rent estimated by Landlord, and the parties shall adjust for any overpayments or underpayments upon the final determination of Base Rent. The failure by the parties to complete the process contemplated under this Section prior to commencement of the Extension Term shall not affect the continuation of the Term or the parties’ obligation to make any adjustments for any overpayments or underpayments for the Base Rent due for the Extension Term promptly after the determination thereof is made.

ARTICLE 4: RENT

4.01.    Base Rent. On the Term Commencement Date and thereafter on the first day of each month during the Term, Tenant shall pay Landlord the monthly installment of Base Rent and the monthly installments of Tenant’s Pro Rata Share of Total Operating Costs, including without limitation Tenant’s Pro Rata Share of Taxes required by Section 4.02, in each case in advance. Rent shall be payable at Landlord’s address or otherwise as Landlord may designate in writing from time to time,

4.02.    Additional Rent.

(a)    General. “Rent” means Base Rent and Additional Rent. Landlord shall estimate in advance (i) all Taxes under Article 5, (ii) all utility costs (unless separately metered to or separately contracted for by Tenant) under Article 6, (iii) all insurance premiums to be paid by Landlord under Article 7 and (iv) all Operating Expenses under Article 8 (individually, all such items in clauses (i) through (iv) being “Operating Costs” and collectively, being “Total Operating Costs”) and Tenant shall pay one-twelfth (l/12th) of Tenant’s Pro Rata Share of such estimated Total Operating Costs monthly in advance together with Base Rent Landlord may adjust its estimates of Total Operating Costs at any time based upon its experience and reasonable anticipation of costs. Such adjustments shall be effective as of the next Rent payment date after notice to Tenant. Within one hundred twenty (120) days after the end of each fiscal year of the Property during the Term, Landlord shall endeavor to give to Tenant a reasonably detailed statement of the Total Operating Costs paid or incurred by Landlord during the preceding fiscal year and Tenant’s Pro Rata Share of such expenses. Within the next thirty (30) days, Tenant shall pay Landlord any underpayment, or Landlord shall credit Tenant with any overpayment, of Tenant’s Pro Rata Share of such Total Operating Costs. If the Term expires or the Lease is terminated as of a date other than the last day of a fiscal year for the Property, Tenant’s payment of Additional Rent pursuant to this Section for such partial fiscal year shall be based on Landlord’s reasonable estimate of the items otherwise includable in Total Operating Costs and shall be made on or before the later of (x) ten (10) days after Landlord delivers such estimate to Tenant or (y) the last day of the Term, with an appropriate payment or refund to be made upon Tenant’s receipt of Landlord’s statement of Total Operating Costs for such fiscal year. This Section shall survive the expiration or earlier termination of the Term.

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(b)    Allocation of Certain Operating Costs; Gross Up. If at any time during the Term Landlord provides services only with respect to particular portions of the Building that include the Premises or incurs other Operating Costs allocable to particular portions of the Building that include the Premises alone, then such Operating Costs shall be charged entirely to those tenants, including Tenant, if applicable, of such portions, notwithstanding the provisions hereof referring to Tenant’s Pro Rata Share. If, during any period for which Landlord’s Operating Costs are being computed, less than all of the Building is occupied by tenants, or if Landlord is not supplying all tenants with the services being supplied hereunder, Operating Costs shall be reasonably estimated and extrapolated by Landlord to determine the Operating Costs that would have been incurred if the Building were fully occupied for such year and such services were being supplied to all tenants, and such estimated and extrapolated amount shall be deemed to be the Operating Costs for such period. Landlord shall make a reasonable allocation of any Operating Costs incurred jointly for the Property and any other property.

(c)    This Lease requires Tenant to pay directly to suppliers, vendors, carriers, contractors, etc., certain insurance premiums, utility costs, personal property taxes, maintenance and repair costs and other expenses. If Landlord pays any of these amounts in accordance with this Lease, Tenant shall reimburse such costs in full with the next monthly Rent payment. Unless this Lease provides otherwise, Tenant shall pay all Additional Rent then due on or before the date for the next monthly Rent payment.

(d)    Audit Right. Provided there is no Event of Default, Tenant shall have the right to cause Landlord’s determination of Tenant’s Pro Rata Share of Total Operating Costs to be audited by an auditor reasonably acceptable to Landlord, one time with respect to any fiscal year, provided notice of Tenant’s desire to so audit is given to Landlord no later than sixty (60) days after Tenant receives an annual statement from Landlord and provided that such review is thereafter commenced and prosecuted by Tenant with due diligence. Any Operating Costs statement or accounting by Landlord shall be binding and conclusive upon Tenant unless (i) Tenant duly requests such review within such 60-day period, and (ii) within three (3) months after such review request, Tenant shall notify Landlord in writing that Tenant disputes the correctness of such statement, specifying the particular respects in which the statement is claimed to be incorrect The auditor conducting the review shall be compensated on an hourly basis and shall not be compensated based upon percentage of overcharges it discovers. No subtenant shall have any right to conduct a review, and no assignee shall conduct a review for any period during which such assignee was not in possession of the Premises. Tenant shall provide Landlord with a true and accurate copy of the audit and related materials provided by such auditor upon request Tenant agrees that all information obtained from any such Operating Costs review, including without limitation, the results of any Operating Costs review shall be kept strictly confidential by Tenant and shall not be disclosed to any other person or entity. If as a result of such audit it is mutually agreed, or if it is ultimately determined, that Landlord’s determination of the foregoing is (i) overstated, or (ii) understated, then in the case of (i) Landlord shall credit the difference against monthly installments of Rent next thereafter coming due (or refund he difference if the Term has ended and Tenant has no further obligation to Landlord), or in the case of (ii) Tenant shall pay to Landlord the amount of such excess. The cost of such audit shall be paid by Tenant; provided, however, if the final, agreed to, determination discloses that Tenant’s Pro Rata Share of Total Operating Costs for the calendar year in question were overstated by more than five percent (5%), then Landlord shall reimburse Tenant, within thirty (30) days after such final, agreed to, determination and Landlord’s receipt of reasonable back-up therefor, for the commercially reasonable costs of the independent audit, not to exceed $2, 500.00.

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4.03.    Late Charge. Tenant acknowledges that if it pays Rent late, Landlord shall incur unanticipated costs, which shall be extremely difficult to ascertain exactly. Such costs include processing and accounting charges, and late charges that may be imposed on Landlord by any mortgagee of the Property. Accordingly, if Landlord does not receive any Rent payment within five (5) days following its due date, Tenant shall pay Landlord a late charge equal to five percent (5%) of the overdue amount. The parties agree that this late charge represents a fair and reasonable estimate of the costs Landlord shall incur by reason of Tenant’s payment default. Payment of the late charge shall not cure Tenant’s payment default or prevent Landlord from exercising other rights and remedies.

4.04.    Interest. Any late Rent shall bear interest from the date due until paid at the rate equal to the Prime Rate plus four percent (4%) per annum except to the extent such interest would cause the total interest to be in excess of that legally permitted. The “Prime Rate” shall mean the prime lending rate per annum published in the Wall Street Journal from time to time. Payment of interest shall not cure Tenant’s payment default or prevent Landlord from exercising other rights and remedies.

4.05.    Method of Payment. Tenant shall pay the Base Rent and Additional Rent to Landlord in advance in equal monthly installments by the first of each calendar month during the Term. Tenant shall make a pro rata payment of Base Rent and Additional Rent for any period of less than a month at the beginning or end of the Term. All payments of Base Rent, Additional Rent and other sums due shall be paid in current U.S, exchange by check drawn on a clearinghouse bank at the Original Address of Landlord or such other place as Landlord may from time to time direct (or if requested by Landlord, by electronic fund transfer), without demand, set-off or other deduction. Without limiting the foregoing, Tenant’s obligation to pay Rent shall be absolute, unconditional, and independent and shall not be discharged or otherwise affected by any law or regulation now or hereafter applicable to the Premises, or any other restriction on Tenant’s use, or, except as expressly provided in herein, any casualty or taking, or any failure by Landlord to perform or other occurrence; and Tenant assumes the risk of the foregoing and waives all rights now or hereafter existing to quit or surrender this Lease or the Premises or any part thereof, or to assert any defense in the nature of constructive eviction to any action seeking to recover Rent; provided, however, the foregoing shall not limit any right that Tenant might otherwise have, subject to the terms and conditions of this Lease including but not limited to Section 10, 02 below, to obtain injunctive relief against Landlord or to take any other action which shall not involve the personal liability of Landlord to respond in monetary damages from Landlord’s assets other than as specifically provided in this Lease. It is intended that Base Rent payable hereunder shall be a net return to Landlord throughout the Term, free of expense, charge, offset, diminution or other deduction whatsoever on account of the Premises (excepting Landlord’s financing expenses, federal and state income taxes of general application, and those expenses that this Lease expressly makes the responsibility of Landlord), and all provisions hereof shall be construed in terms of such intent.

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4.06.    Tenant’s Pro Rata Share.

(a)    Tenant’s Pro Rata Share of Taxes is equal to the product of the rentable square footage of the Premises multiplied by Landlord’s PSF Taxes (hereafter defined) for each fiscal year, or ratable portion thereof, included in the Term. “Landlord’s PSF Taxes” shall mean the Taxes (as defined in Section 5.02) divided by the rentable square footage of the Building, as same may be adjusted by Landlord from time to time for a remeasurement of or changes in the physical size of the Premises, the Building and/or the Project (as defined below), whether such changes in size are due to an addition to or a sale or conveyance of a portion of the Building, the Project or otherwise. As of the date hereof, the rentable floor area of the Building is conclusively deemed to be 187, 507 rentable square feet.

(b)    Tenant’s Pro Rata Share of Operating Expenses, utilities and insurance is equal to the product of the rentable square footage of the Premises multiplied by Landlord’s PSF Operating Expenses (hereafter defined) for each calendar year, or ratable portion thereof, included in the Term. “Landlord’s PSF Operating Expenses” shall mean Operating Expenses (as defined in Section 8.01), utilities and insurance costs divided by the rentable square footage of the Building or the portion thereof with respect to which such Operating Expenses, utilities and insurance costs are determined.

(c)    Tenant’s Pro Rata Share shall be the percentage set forth in Article 1, which percentage has been determined by dividing the total number of rentable square feet in the Premises by the total number of rentable square feet in the Building, and multiplying the resulting quotient by one hundred (100). As of the date hereof, the rentable floor area of the Premises is as set forth in Article 1 and the rentable floor area of the Building is conclusively deemed to be 187, 507 rentable square feet. The rentable square footage of the Building may be adjusted by Landlord from time to time for a remeasurement of or changes in the physical size of the Premises, the Building and/or the Project (as defined below), whether such changes in size are due to an addition to or a sale or conveyance of a portion of the Building, the Project or otherwise. Without limiting the generality of the foregoing, Landlord may equitably adjust Tenant’s Pro Rata Share upon Tenant’s use of the Utility Services as reasonably estimated and equitably determined by Landlord based upon factors such as the intensity of use of such Utility Services by Tenant such that Tenant shall pay the portion of such charges reasonably consistent with Tenant’s use thereof.

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ARTICLE 5: TAXES

5.01.    Taxes. Tenant covenants and agrees to pay to Landlord as Additional Rent Tenant’s Pro Rata Share of the Taxes for each fiscal tax period, or ratable portion thereof, included in the Lease Term. If Landlord receives a refund of any such Taxes, Landlord shall pay Tenant Tenant’s Pro Rata Share of the refund after deducting Landlord’s costs and expenses incurred in obtaining the refund. Tenant shall make estimated payments on account of Taxes in monthly installments on the first day of each month, in amounts reasonably estimated from time to time by Landlord pursuant to Section 4.02(a).

5.02.    Definition of “Taxes”. “Taxes” means all taxes, assessments, betterments, excises, user fees and all other governmental charges and fees of any kind or nature, or impositions or agreed payments in lieu thereof or voluntary payments made in connection with the provision of governmental services or improvements of benefit to the Building or the Property (including any so-called linkage, impact, or voluntary betterment payments), and all penalties and interest thereon (if due to Tenant’s failure to make timely payments), assessed or imposed against the Premises or the property of which the Premises are a part (including, without limitation, any personal property taxes levied on such property or on fixtures or equipment used in connection therewith), other than a federal or state income tax of general application. If during the Term the present system of ad valorem taxation of property shall be changed so that, in lieu of or in addition to the whole or any part of such ad valorem tax there shall be assessed, levied or imposed on such property or Premises or on Landlord any kind or nature of federal, state, county, municipal or other governmental capital levy, income, sales, franchise, excise or similar tax, assessment, levy, charge or fee (as distinct from the federal and state income tax in effect on the Date of Lease) measured by or based in whole or in part upon Building valuation, mortgage valuation, rents, services or any other incidents, benefits or measures of real property or real property operations, then any and all of such taxes, assessments, levies, charges and fees shall be included within the term of Taxes. Taxes shall also include expenses, including fees of attorneys, appraisers and other consultants, incurred in connection with any efforts to obtain abatements or reduction or to assure maintenance of Taxes for any year wholly or partially included in the Term, whether or not successful and whether or not such efforts involved filing of actual abatement applications or initiation of formal proceedings.

5.03.    Personal Property Taxes. Tenant shall pay directly all taxes charged against Tenant Property (as defined in Section 10.06). Tenant shall use commercially reasonable efforts to have personal property taxed separately from the Property. Landlord shall notify Tenant if any of Tenant’s personal property is taxed with the Property, and Tenant shall pay such taxes to Landlord within fifteen (15) days of such notice.

ARTICLE 6: UTILITIES AND LANDLORD SERVICES

6.01.    Utility Services. Tenant shall provide and pay all charges and deposits for gas, water, sewer, electricity, and other energy, utilities and services used or consumed on the Premises (“Utility Services”) during the Term which now or hereafter separately serve the Premises, or are not expressly to be provided by Landlord elsewhere hereunder. If any such Utility Services are not separately metered, Tenant shall pay the cost of the same as part of the Operating Costs payable hereunder. It is understood that the electrical service for the Premises shall be either separately metered or sub or check metered to measure Tenant’s consumption of electricity. If such electrical service is separately metered Tenant shall pay directly to the utility supplier, as Additional Rent hereunder, all electrical service charges before delinquency. If such electrical service is sub or check metered, Landlord shall calculate the electrical service charge based on Tenant’s actual usage of electricity and Tenant shall pay same to Landlord, as Additional Rent, within fifteen (15) days of billing therefore. It is understood and agreed that except as may be expressly provided hereunder, Landlord shall be under no obligation whatsoever to furnish any such services to the Premises, and shall not be liable for (nor suffer any reduction in any rent on account of) any interruption or failure in the supply of the same.

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If the any such Utility Services are not separately metered, Landlord reserves the right, at any time during the Term, to install a monitor or check meter to measure Tenant’s consumption of such Utility Service(s), in which event Landlord shall calculate the applicable Utility Services charges based on Tenant’s actual usage thereof, rather than as otherwise provided herein. To the extent permitted by law, Landlord shall have the right at any time and from time to time during the Term to contract for or purchase one or more Utility Services from any company or third-party providing Utility Services (“Utility Service Provider”). Tenant agrees reasonably to cooperate with Landlord and the Utility Service Providers and at all times as reasonably necessary, and on reasonable advance notice (except in the event of emergency), shall allow Landlord and the Utility Service Providers reasonable access to any utility lines, equipment, feeders, risers, fixtures, wiring and any other such machinery or personal property within the Premises and associated with the delivery of Utility Services.

6.02.    Landlord Services. Landlord agrees to furnish reasonable heat and air conditioning (HVAC) to the Premises and to common hallways and lavatories, if any, during normal business hours on regular business days during the heating or air conditioning season, as applicable, to light common passageways twenty-four (24) hours a day, to provide hot water to common lavatories, and to clean common areas, common area glass, common lavatories and glass main entry doorways to the Premises Mondays through Fridays, in substantially the same fashion as is typical for comparable first class office and laboratory projects in the Lexington area, subject to interruption due to accident, to the making of repairs, alterations or improvements, to labor difficulties, to trouble in obtaining fuel, electricity, service or supplies from the sources from which they are usually obtained for such Building, governmental restraints, or to any cause beyond the Landlord’s control. To the maximum extent this agreement may be made effective according to law (including the limitations set forth in M.G.L. c. 186, §15), but subject to Tenant’s insurance requirements hereunder and Section 7.03, in no event shall Landlord be liable for any interruption or delay in any of the above services for any of such causes. For the purposes of this clause, reasonable heating of common areas shall be provided between the hours of 8:00 a.m. to 6:00 p.m. Monday through Friday and 8:00 a.m. to 1:00 p.m. on Saturday during the months from November through April (holidays excepted). Reasonable cooling of common areas shall be provided between the hours of 8:00 a.m. and 6:00 p.m. Monday through Friday and 8:00 a.m. to 1:00 p.m. on Saturday during the cooling season (holidays excepted). If Tenant requests Landlord to provide additional heat or air conditioning outside of such hours, Tenant shall pay therefor (within fifteen (15) days after billing) at reasonable rates established by Landlord from time to time. Notwithstanding the foregoing, Tenant shall be entitled to a proportionate abatement of Base Rent in the event of a Landlord Service Interruption (as defined below), from the first (1st) business day following the Landlord Service Interruption Cure Period (as defined below) until the Landlord Service Interruption is cured. For the purposes hereof, a “Landlord Service Interruption” shall occur in the event (i) the Premises, or any material portion thereof, shall lack any service which Landlord is required to provide hereunder thereby rendering the Premises, or the applicable portion, untenantable for the entirety of the Landlord Service Interruption Cure Period (as defined below), (ii) such lack of service was not caused by Tenant, its employees, contractors, invitees or agents or by a casualty (in which event Section 12.01 shall control); (iii) Tenant in fact ceases to use the entire Premises, or the applicable portion, for the entirety of the Landlord Service Interruption Cure Period; and (iv) such interruption of service was the result of causes, events or circumstances within the Landlord’s reasonable control and the cure of such interruption is within Landlord’s reasonable control. For the purposes hereof, the “Landlord Service Interruption Cure Period” shall be defined as five (5) consecutive business days after Landlord’s receipt of written notice from Tenant of the Landlord Service Interruption. In any event, Landlord shall use commercially reasonable and diligent efforts to resolve and/or mitigate any such interruption of services.

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6.03.    Excess Usage by Tenant. Tenant shall not introduce to the Premises personnel, fixtures or equipment which (individually or in the aggregate) exceed those used by the average Building tenant or overload the capacity of the electrical, heating, ventilating and air conditioning, mechanical, plumbing or other utility systems serving the Premises or generate above average heat, noise or vibration at the Premises. If Tenant uses the Premises or installs fixtures or equipment in such a manner as would so overload said systems, as reasonably determined by Landlord, then, in addition to any other remedies Landlord may have, Tenant shall pay, as Additional Rent, within ten (10) days of billing therefor, the cost of providing and installing any additional equipment, facilities or services that may be required as a result thereof, and for any repairs or damage resulting therefrom.

ARTICLE 7: INSURANCE

7.01.    Coverages. Tenant shall, at its own expense, maintain and keep in force, or cause to be maintained and kept in force by any general contractors, sub-contractors or third party entities where required by contract, throughout the term of this Lease and/or alteration or construction period and for such longer period, if any, Tenant remains in occupancy of the Premises, the following insurance coverages:

(a)    Property Insurance. “All-Risk” or “Special” Form property insurance, and/or Builders Risk coverage for renovation projects, including, without limitation, coverage for fire, and earthquake; boiler and machinery (if applicable); sprinkler damage; vandalism; malicious mischief coverage on all equipment, furniture, fixtures, fittings, Initial Tenant Improvements, Tenant Work, Tenant Property or other improvements and betterments installed in or about the Premises by or on behalf of Tenant, business income, extra expense, merchandise, inventory/stock, contents, and personal property of Tenant (or those taking by or through Tenant) located on or in the Premises. Such insurance shall be in an amount equal to the full replacement cost of the aggregate of the foregoing and shall provide coverage comparable to the coverage in the standard ISO “All-Risk” or “Special”, Form, when such coverage is supplemented with the coverages required above. This property policy shall also include coverage for plate glass, where required by written contract.

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(b)    Liability Insurance. Commercial General Liability insurance against any and all claims for personal injury, death or property damage occurring in, or about the Premises and arising out of Tenant’s operations on the Premises, or Tenant’s agents’, invitees’, sublessees, use or occupancy of the Premises. Such insurance shall have a limit of not less than One Million Dollars ($1, 000, 000) per occurrence with a Two Million Dollar ($2, 000, 000) aggregate limit Such insurance shall contain an extended (broad form) liability endorsement, including contractual liability coverage (including this Lease, and Tenant’s indemnity obligations hereunder). Such liability insurance shall be primary and not contributing to any insurance available to Landlord, and Landlord’s insurance (if any) shall be in excess thereto. Tenant’s commercial general liability insurance policy shall include Landlord, Landlord’s Management Agent, Landlord’s mortgagees and Landlord’s designees as additional insureds, and shall provide that such parties may, although additional insureds, recover for any loss suffered by Tenant’s negligence.

(c)    Umbrella / Excess Liability Insurance. The foregoing liability limits shall be adequate as long as Tenant maintains an Umbrella policy limit of not less than Three Million Dollars ($3, 000, 000) per occurrence. Should Tenant not maintain an Umbrella policy with such limits, then the limits of the underlying Commercial General Liability policy shall be increased to Two Million Dollars ($2, 000, 000) per occurrence and Four Million Dollars ($4,000,000) aggregate.

(d)    Other. Such other insurance as Landlord may reasonably require, from time to time, and as may be required by law, including, without limitation (i) workers’ compensation insurance with a limit of liability as required by law to be maintained; (ii) employer’s liability insurance with a minimum limit of coverage of Two Million Dollars ($2, 000, 000); and (iii) business interruption and extra expense insurance coverage(s) reasonably satisfactory to Landlord.

(e)    Form of the Policies. Tenant shall have the right to provide insurance coverage which it is obligated to carry pursuant to the terms hereof in a blanket policy, provided such policy expressly affords coverage to the Premises and to Landlord as required by this Lease.

(f)    Failure by Tenant to Obtain Insurance. If Tenant does not procure the insurance required pursuant to this Section, or keep the same in full force and effect, Landlord may, but shall not be obligated to, take out the necessary insurance and pay the premium therefor after notice thereof to Tenant, and Tenant shall repay to Landlord, as Additional Rent, the amount so paid promptly upon demand. In addition, Landlord may recover from Tenant, as Additional Rent, any and all reasonable expenses (including attorneys’ fees) and damages which Landlord may sustain by reason of the failure by Tenant to obtain and maintain such insurance, it being expressly declared that the expenses and damages of Landlord shall not be limited to the amount of the premiums thereon.

(g)    Contractor Insurance. Tenant shall cause all contractors and subcontractors to maintain during any period of Tenant Work (including the Initial Tenant Improvements) the insurance described on Exhibit D attached hereto.

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(h)    Deductibles. Tenant’s insurance policies shall not include deductibles in excess of Five Thousand Dollars ($5, 000) without Landlord’s prior written consent If any of the above insurances have deductibles or self-insured retentions, Tenant and/or contractor (policy Named Insured) shall be responsible for the deductible amount.

(i)    General Requirements. All of the insurance policies required in this Section (“Insurance Requirements”) shall be written by insurance companies which are licensed to do business in the state where the Property is located, or obtained through a duly authorized surplus lines insurance agent or otherwise in conformity with the laws of such state, with an A.M. Best rating of at least “A” and a financial size category of not less than “VII”. The liability policy(ies) shall name, as additional insureds, Landlord, Landlord’s Management Agent, Landlord’s mortgagees and Landlord’s designees, and provide thirty (30) days’ notice of cancellation, non-renewal, or material change in the terms and conditions of coverage. Tenant shall provide Landlord with certificates of insurance upon request, prior to move-in date, prior to commencement of the Tenant/contractor work, and within thirty (30) days of coverage inception and subsequent renewals or rewrites/replacements of any cancelled/non-renewed policies.

7.02.    Avoid Action Increasing Rates. Tenant shall comply with Sections 9.01, 9.02, 9.03 and 9.04 and in addition shall not, directly or indirectly, use the Premises in any way that is prohibited by law or dangerous to people or property or that may jeopardize or increase the cost of any insurance coverage or require additional insurance. Tenant shall cure any breach of this Section within ten (10) days after notice from Landlord (or Tenant’s independent knowledge of such breach) by (i) stopping any use that jeopardizes any insurance coverage or increases its cost and (ii) reimbursing Landlord for the increased cost of insurance. Tenant shall have no further notice or cure right under Article 14 for any such breach. Tenant shall reimburse Landlord for all of Landlord’s costs incurred in providing any insurance that is attributable to any special endorsement or increase in premium resulting from the business or operations of Tenant, and any special or extraordinary risks or hazards resulting therefrom, including, without limitation, any risks or hazards associated with the generation, storage and disposal of Environmental Substances.

7.03.    Waiver of Subrogation. Landlord and Tenant each waive any and every claim for recovery from the other for any and all loss of or damage to the Property or any part of it, or to any of its contents, which loss or damage is covered by valid and collectible property insurance. Landlord waives any and every such claim against Tenant that would have been covered had the insurance policies required to be maintained by Landlord by this Lease been in force, to the extent that such loss or damage would have been recoverable under such policies. Tenant waives any and every such claim against Landlord that would have been covered had the insurance policies required to be maintained by Tenant under this Lease been in force, to the extent that such loss or damage would have been recoverable under such policies. This mutual waiver precludes the assignment of any such claim by subrogation (or otherwise) to an insurance company (or any other person), and Landlord and Tenant each agree to give written notice of this waiver to each insurance company that has issued or shall issue any property insurance policy to it, and to have the policy properly endorsed, if necessary, to prevent invalidation of the insurance coverage because of this waiver.

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7.04.    Landlord’s Insurance. Landlord shall purchase and maintain during the Term, with insurance companies qualified to do business in the state where the Property is located insurance that may include the following: (i) commercial general liability insurance for incidents occurring in the common areas, with coverage for premises/operations, personal and advertising injury, products/completed operations and contractual liability for bodily injury and property damage per occurrence, together with such other coverages and risks as Landlord shall reasonably decide or a mortgagee may require; (ii) property insurance covering property damage to the Building, excluding the Initial Tenant Improvements and any other Tenant Work, and loss of rental income, for full replacement cost value of the Building with co-insurance waived by inclusion of an agreed amount endorsement; and (iii) such other coverage(s) as may be required by Landlord’s mortgagee or otherwise be deemed commercially reasonable by Landlord. As set forth in Section 4.02? the cost thereof shall be borne by Tenant and other tenants.

ARTICLE 8: OPERATING EXPENSES

8.01.    Operating Expenses.

(a)    “Operating Expenses” shall mean all costs and expenses associated with the ownership, operation, management, maintenance and repair of the Building and Property and of all heating, ventilating, air conditioning, plumbing, electrical, utility and safety systems for the Building. “Common Elements” shall mean all areas in the Building available for the common use of tenants of the Building and not leased or held for the exclusive use of Tenant or other tenants, including, but not limited to, the common cafe and common parking areas, driveways, sidewalks, access roads, plazas, landscaping and planted areas located in the Building or on the Property. Operating Expenses include, without limitation, the costs and expenses incurred in connection with the following: compliance with Landlord’s obligations under Section 10.03; planting and landscaping; snow plowing and removal; utility, water and sewage services; maintenance of signs; supplies, materials and equipment purchased or rented, total wage and salary costs paid to, and all contract payments made on account of, all persons engaged in the operation, maintenance, security, cleaning and repair of the Property and Common Elements, including Social Security, old age and unemployment taxes and so-called “fringe benefits”; services generally furnished to tenants of the Building; maintenance, repair and replacement of Building and Common Elements equipment and components; utilities consumed and expenses incurred in the operation, maintenance and repair of the Property and Common Elements; costs incurred under any reciprocal easement agreements benefiting the Property; costs incurred by Landlord to comply with the terms and conditions of any governmental approvals affecting operations of the Property; the amortized portion, properly attributable to the year in question, of the cost, with interest thereon at a rate reasonably determined by Landlord, of any capital repairs, improvements or replacements made to the Property, by Landlord; workers’ compensation insurance and property, liability and other insurance premiums; personal property taxes; rental or lease payments paid by Landlord for rented or leased personal property used in the operation or maintenance of the Property and Common Elements; fees for required licenses and permits; losses or subsidies paid or incurred by Landlord in operating the common cafe; routine maintenance and repair of parking areas and paving (including sweeping, striping, repairing, resurfacing, and repaving); refuse removal; security; reasonable reserves, including for roof replacement and exterior painting; and property management fees. Operating Expenses shall also include the Building’s share (as reasonably determined and allocated by Landlord) of: (i) the costs incurred by Landlord in operating, maintaining, repairing, insuring and paying real estate taxes upon any common facilities of the office park or development (including, without limitation, the common facilities from time to time serving the Building in common with other buildings or parcels of land) of which the Property may be a part, from time to time, such as any so-called “loop” access roads, retention ponds, sewer and other utility lines, amenities and the like; (ii) shuttle bus service (if and so long as Landlord shall provide the same); (iii) the actual or imputed cost of the space occupied by on-the-grounds building attendant(s) and related personnel and the cost of administrative and or service personnel whose duties are not limited solely to the Building, as allocated to the Building by Landlord; and (iv) payments made by Landlord under any easement, license, operating agreement, declaration, restrictive covenant, or instrument pertaining to the payment or sharing of costs among park or development property owners. Landlord may use third parties or affiliates to perform any of the foregoing services, and the cost thereof shall be included in Operating Expenses. Costs referred to in this Section shall be ascertained in accordance with generally accepted accounting principles, including allowances for appropriate reserves, and allocated to appropriate fiscal periods on the accrual method of accounting.

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(b)    Operating Expenses shall not include: the cost of casualty repairs to the extent covered by insurance (except for reasonable deductibles paid by Landlord under insurance policies maintained by Landlord); costs associated with the operation of the business of Landlord and/or the sale and/or financing of the Building, as distinguished from the cost of Building operations, maintenance and repair; and costs of disputes between Landlord and its employees, tenants or contractors; mortgage, interest and other financing costs; depreciation on the Building or other systems, fixtures or equipment in the Building; cost of any improvements to a particular tenant’s space; leasing fees and commissions, and advertising costs in connection with the Building; expenses for which Landlord, by the terms of this Lease or any other lease, makes a separate charge to Tenant or any other tenant and is entitled to reimbursement therefrom; any capital expenditure which Landlord is not entitled to include in Operating Expenses (e.g., except as expressly provided in Subsection (a) above); and salaries of employees above the grade of building superintendent or building manager (or those performing the tasks of such parties regardless of title).

(c)    Tenant shall pay Tenant’s Pro Rata Share of Operating Expenses in accordance with Section 4.02.

ARTICLE 9: USE OF PREMISES

9.01.    Permitted Uses. Tenant may use the Premises only for the Permitted Uses described in Article 1, and for no other purpose(s). Tenant shall keep the Premises equipped with appropriate safety appliances to the extent required by applicable laws or insurance requirements.

9.02.    Indemnification. Tenant shall assume exclusive control of all areas of the Premises, including all improvements, utilities, equipment, and facilities therein. Tenant is responsible for the Premises and any Tenant’s improvements, equipment, facilities and installations, wherever located on the Property and all liabilities, including, without limitation, tort liabilities, incident thereto. To the maximum extent this agreement may be made effective according to law (including the limitations set forth in M.G.L. c. 186, §15), but subject to Tenant’s insurance requirements hereunder and Section 7.03? Tenant shall indemnify, save harmless and defend Landlord and Landlord’s members, managers, officers, mortgagees, agents, employees, independent contractors, invitees, Landlord’s Managing Agent and other persons acting under them (collectively, “Indemnitees”) from and against all liability, claims, damages or costs (including reasonable attorneys’ fees) arising in whole or in part out of (i) any injury, loss, theft or damage (a) to any person or property while on or about the Premises or (b) to Tenant or Tenant’s agents, employees, independent contractors, suppliers or invitees (each a “Tenant Party”) while on or about the Property or the Building, except, in either case, to the extent caused by the negligence or willful misconduct of any Indemnitee; (ii) any injury, loss, theft or damage to any person or property, other than a Tenant Party, while on or about the Property or the Building to the extent caused by the negligence or willful misconduct of a Tenant Party; (iii) any condition within the Premises or, to the extent arising from the acts or omissions of Tenant, the Property or the Building; (iv) failure to comply with any Lease covenant by Tenant; or (v) the use of the Premises (or, to the extent arising from the acts or omissions of Tenant, the Property or the Building) by, or any act or omission of, Tenant or persons claiming by, through or under Tenant, or any of its agents, employees, independent contractors, suppliers or invitees, in each case paying any cost to Landlord on demand as Additional Rent. The provisions of this Section shall survive the expiration or earlier termination of this Lease.

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9.03.    Compliance With Legal Requirements. Tenant shall not cause or permit the Premises, or, to the extent arising from the acts or omissions of Tenant, the Property or the Building to be used in any way that violates any law, code, ordinance, restrictive covenant, encumbrance, governmental regulation, order, permit, approval, variance, covenants or restrictions of record or any provision of the Lease (each a “Legal Requirement”), annoys or interferes with the rights of tenants of the Building, or constitutes a nuisance or waste. Tenant shall obtain, maintain and pay for all permits and approvals and shall promptly take all actions necessary to comply with all Legal Requirements, including, without limitation, the Occupational Safety and Health Act, applicable to Tenant’s use of the Premises, the Property or the Building. Tenant shall maintain in full force and effect all certifications or permissions to provide its services required by any authority having jurisdiction to authorize, franchise or regulate such services. Tenant shall be solely responsible for procuring and complying at all times with any and all necessary permits and approvals directly or indirectly relating or incident to: the conduct of its activities on the Premises; its scientific experimentation, transportation, storage, handling, use and disposal of any chemical or radioactive or bacteriological or pathological substances or organisms or other hazardous wastes or environmentally dangerous substances or materials or medical waste or animals or laboratory specimens. Within ten (10) days of a request by Landlord, which request shall be made not more than once during each period of twelve (12) consecutive months during the Term hereof, unless otherwise requested by any mortgagee of Landlord, Tenant shall furnish Landlord with copies of all such permits and approvals that Tenant possesses or has obtained together with a certificate certifying that such permits are all of the permits that Tenant possesses or has obtained with respect to the Premises. Tenant shall promptly give written notice to Landlord of any warnings or violations involving the Premises (or Tenant’s use or occupancy thereof) relative to the above received from any federal, state or municipal agency or by any court of law and shall promptly cure the conditions causing any such warnings or violations. Tenant shall not be deemed to be in default of its obligations under the preceding sentence to promptly cure any condition causing any such violation in the event that, in lieu of such cure, Tenant shall contest the validity of such violation by appellate or other proceedings permitted under applicable law, provided that: (i) any such contest is made reasonably and in good faith, (ii) Tenant makes provisions, including, without limitation, posting bond(s) or giving other security, acceptable to Landlord to protect Landlord, the Building and the Property from any liability, costs, damages or expenses arising in connection with such violation and failure to cure, (iii) Tenant shall agree to indemnify, defend (with counsel reasonably acceptable to Landlord) and hold Landlord harmless from and against any and all liability, costs, damages, or expenses arising in connection with such condition and/or violation, (iv) Tenant shall promptly cure any violation in the event that its appeal of such violation is overruled or rejected, and (v) Tenant’s decision to delay such cure shall not, in Landlord’s good faith determination, be likely to result in any actual or threatened bodily injury, property damage, or any civil or criminal liability to Landlord, any tenant or occupant of the Building or the Property, or any other person or entity.

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9.04.    Environmental Substances. “Environmental Law(s)” means all statutes, laws, rules, regulations, codes, ordinances, standards, guidelines, authorizations and orders of federal, state and local public authorities pertaining to any of the Environmental Substances or to environmental compliance, contamination, cleanup or disclosures of any release or threat of release to the environment, of any hazardous, biological, chemical, radioactive or toxic substances, wastes or materials, any pollutants or contaminants that are included under or regulated by any municipal, county, state or federal statutes, laws, rules, regulations, codes, ordinances, standards, guidelines, authorizations or orders, including, without limitation, the Toxic Substances Control Act, 15 U.S.C. § 2601, et seq.; the Clean Water Act, 33 U.S.C. § 1251, et seq.: the Clean Air Act, 42 U.S.C. § 7401, et seq.; the Safe Drinking Water Act, 42 U.S.C. § 300f-300j, et seq.; the Federal Water Pollution Control Act, 33 U.S.C. § 1321, et seq.; the Comprehensive Environmental Response, Compensation and Liability Act of 1980, 42 U.S.C. Section 9601 et seq.; the Federal Resource Conservation and Recovery Act, 42 U.S.C. Section 6901 et seq.; the Massachusetts Hazardous Waste Management Act, as amended, M.G.L. Chapter 21C, and the Massachusetts Oil and Hazardous Material Release Prevention Act, as amended, M.G.L., Chapter 21E, as any of the same are from time to time amended, and the rules and regulations promulgated thereunder, and any judicial or administrative interpretation thereof, including any judicial or administrative orders or judgments, and all other federal, state and local statutes, laws, rules, regulations, codes, ordinances, standards, guidelines, authorizations and orders regulating the generation, storage, containment or disposal of any Environmental Substances, including, but not limited to, those relating to lead paint, radon gas, asbestos, storage and disposal of oil, biological, chemical, radioactive and hazardous wastes, substances and materials, and underground and above ground oil storage tanks; and any amendments, modifications or supplements of any of the foregoing.

“Environmental Substances” means, but shall not be limited to, any hazardous substances, hazardous waste, environmental, biological, chemical, radioactive substances, oil, petroleum products and any waste or substance, which because of its quantitative concentration, chemical, biological, radioactive, flammable, explosive, infectious or other characteristics, constitutes or may reasonably be expected to constitute or contribute to a danger or hazard to public health, safety or welfare or to the environment, or that would trigger any employee or community “right-to-know” requirements adopted by any federal, state or local governing or regulatory body, or for which any such body has adopted any requirements for the preparation or distribution of a materials safety data sheet (“MSDS”), including, without limitation, any asbestos (whether or not friable) and any asbestos- containing materials, lead paint, waste oils, solvents and chlorinated oils, polychlorinated biphenyls (PCBs), toxic metals, etchants, pickling and plating wastes, explosives, reactive metals and compounds, pesticides, herbicides, radon gas, urea formaldehyde foam insulation and chemical, biological and radioactive wastes, or any other similar materials that are mentioned under or regulated by any Environmental Law; and the regulations adopted under these acts, and including any other products or materials subsequently found by an authority of competent jurisdiction to have adverse effects on the environment or the health and safety of persons.

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Tenant shall neither cause or permit (by Tenant or any party taking by or through Tenant) any Environmental Substances to be generated, produced, brought upon, used, stored, treated or disposed of in or about or on the Property or Building by Tenant, nor permit or suffer persons acting under Tenant, to do the same, whether with or without negligence, without (i) Landlord’s prior written consent, which consent shall not be unreasonably withheld, conditioned or delayed (provided that Landlord’s consent shall not be required for typical office products in reasonable quantities) and (ii) complying with all applicable Environmental Laws and Legal Requirements pertaining to the transportation, storage, use or disposal of such Environmental Substances, including obtaining proper permits and approvals and providing Landlord the applicable MSDS for each Environmental Substance. Landlord may take into account any factors or facts that Landlord reasonably believes relevant in determining whether to grant its consent. Tenant is required to adhere to and comply with the allowable quantities of Environmental Substances that are allocated to them by the Landlord’s flammable and/or Environmental Substances matrix, from time to time. Landlord consents to Tenant’s use of the Environmental Substances (and quantities) listed in Exhibit G. From time to time at Landlord’s request, Tenant shall execute affidavits, representations and the like in commercially reasonable forms concerning Tenant’s best knowledge and belief, after due inquiry, regarding the presence or absence of Environmental Substances on the Premises, the Property or the Building. Tenant agrees to pay the reasonable cost of any environmental inspection or assessment requested by any lender that holds a security interest in the Property or this Lease, or by any insurance carrier, to the extent that such inspection or assessment pertains to any release, threat of release, contamination, claim of contamination, loss or damage or determination of condition in the Premises arising from any act or omission of Tenant, its agents, employees, independent contractors, or invitees or otherwise arising from Tenant’s breach of its obligations hereunder. In addition, at Landlord’s request, Tenant shall promptly provide to Landlord all MSDSs for products used within the Premises.

If any transportation, storage, use or disposal of Environmental Substances On or about the Property or Building by Tenant, its agents, employees, independent contractors, or invitees results in any escape to, release to, threat of release to or contamination of the soil, surface or ground water, sewage system or ambient air or any loss or damage to person or property, Tenant agrees to: (a) notify Landlord immediately of the occurrence; (b) after consultation with Landlord, clean up the occurrence in full compliance with all applicable statutes, regulations and standards; and (c) indemnify, defend and hold Landlord, and the Indemnitees harmless from and against any claims, suits, causes of action, costs and fees, including reasonable attorneys’ fees and costs, arising from or connected with any such occurrence. In the event of such occurrence, Tenant agrees to cooperate fully with Landlord and provide such documents, affidavits, information and actions as may be reasonably requested by Landlord (1) to comply with any Environmental Law or Legal Requirement, (2) to comply with any request of any mortgagee or tenant and/or (3) for any other reason deemed reasonably necessary by Landlord in its sole discretion. In the event of any such occurrence that is required to be reported to a governmental authority under any Environmental Law or Legal Requirement, Tenant shall simultaneously deliver to Landlord copies of any notices given or received by Tenant and shall promptly pay when due any fine or assessment against Landlord, Tenant or the Premises or Property relating to such occurrence.

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9.05.    Signs and Auctions. No sign, antenna or other structure or thing, shall be erected or placed on the Premises or any part of the exterior of the Building or erected so as to be visible from the exterior of the Building without first securing the written consent of the Landlord. Tenant shall not conduct or permit any auctions or sheriffs sales at the Property. Landlord, at Landlord’s cost, shall provide Tenant identification on existing multi-tenant signs or directories at the entrance to Building A and in the parking garage, as appropriate. Such signs will be mutually agreed upon by Landlord and Tenant provided that all such signs will be consistent with standard Building signage and will conform to local regulations.

9.06.    Landlord’s Access. Landlord or its agents may enter the Premises at all reasonable times to show the Premises to potential buyers, investors or tenants or other parties; to inspect and conduct tests in order to monitor Tenant’s compliance with Legal Requirements governing Environmental Substances; for purposes described in Sections 2.01, 9.04, 10.03 and/or 10.04(b) or for any other purpose Landlord reasonably deems necessary. Landlord shall give Tenant commercially reasonable prior notice (which may be oral) of such entry. However, in case of emergency, Landlord may enter any part of the Premises without prior notice to Tenant’s representative and shall make reasonable efforts to notify Tenant.

ARTICLE 10: CONDITION AND MAINTENANCE OF PREMISES AND PROPERTY

10.01.    Existing Conditions. Tenant shall accept the Premises and Property in their condition as of the Term Commencement Date “as is” and subject to all Legal Requirements. As of the Commencement Date, the roof and all Core Building Systems (as defined herein) shall be in good working condition and suitable for general office, research and laboratory uses without taking into account Tenant’s specific use or manner of use. Tenant acknowledges that except for any express representations in this Lease, neither Landlord nor any person acting under Landlord has made any representation as to the condition of the Property or the suitability of the Property for Tenant, s intended use. Tenant represents and warrants that Tenant has made its own inspection and inquiry regarding the Property and is not relying on any representations of Landlord or any Broker or persons acting under either of them.

10.02.    Exemption and Limitation of Landlord’s Liability.

(a)    Exemption of Landlord from Liability. Tenant shall insure its personal property under a full replacement cost property insurance policy. To the maximum extent this agreement may be made effective according to law (including the limitations set forth in M.G.L. c. 186, §15), but subject to Tenant’s insurance requirements hereunder and Section 7.03, Landlord shall not be liable for any damage or injury to the person, property or business (including loss of revenue, profits or data) of Tenant, Tenant’s employees, agents, contractors, or invitees, or any other person on or about the Property or the Building. This exemption shall apply whether such damage or injury is caused by (among other things): (i) fire, steam, electricity, water, gas, sewage, sewer gas or odors, snow, ice, frost or rain; (ii) the breakage, leakage, obstruction or other defects of pipes, faucets, sprinklers, wires, appliances, plumbing, windows, air conditioning or lighting fixtures or any other cause; (iii) any other casualty or any Taking; (iv) theft; (v) conditions in or about Property or the Building or from other sources or places; or (vi) any act Or omission of any other tenant.

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(b)    Limitation On Landlord’s Liability. Tenant agrees that Landlord shall be liable only for breaches of its covenants occurring while it is owner of the Property (provided, however, that if Landlord from time to time is lessee of the ground or improvements constituting the Building, then Landlord’s period of ownership of the Property shall be deemed to mean only that period while Landlord holds such leasehold interest). Upon any sale or transfer of the Building, the transferor Landlord (including any mortgagee) shall be freed of any liability or obligation thereafter arising and, subject to Section 9.02, Tenant shall look solely to the transferee Landlord as aforesaid for satisfaction of such liability or obligation. Tenant and each person acting under Tenant agrees to look solely to Landlord’s interest from time to time in the Property for satisfaction of any claim against Landlord. No owner, trustee, beneficiary, partner, member, manager, agent, or employee of Landlord (or of any mortgagee or any lender or ground or improvements lessor) nor any person acting under any of them shall ever be personally or individually liable to Tenant or any person claiming under or through Tenant for or on account of any default by Landlord or failure by Landlord to perform any of its obligations hereunder, or for or on account of any amount or obligations that may be or become due under or in connection with this Lease or the Premises; nor shall it or they ever be answerable or liable in any judicial proceeding or order beyond the extent of their interest in the Property. No deficit capital account of any member or partner of Landlord shall be deemed to be a liability of such member or partner or an asset of Landlord. Any lien obtained to enforce any judgment against Landlord shall be subject and subordinate to any mortgage encumbering the Property. In no event shall Landlord (or any such persons) ever be liable to Tenant for indirect or consequential damages.

10.03.    Landlord’s Obligations.

(a)    Repair and Maintenance. Subject to the provisions of Article 12, and except for damage caused by any act or omission of Tenant or persons acting under Tenant, Landlord shall keep the common areas of the Building (including, without limitation, common elevators, common driveways and walkways and common parking areas) and the foundation, roof, Core Building Systems (to the extent not serving the Premises or another tenant’s premises exclusively), structural supports, exterior windows and exterior walls of the Building in good order, condition and repair reasonable wear and tear excepted in a manner commensurate with first class biotech/life science complexes in the greater Boston area and in compliance with applicable laws and regulations. Landlord shall be responsible for snow and ice removal from the walkways, driveways and parking areas. Landlord shall provide first-class janitorial service in the Common Elements the cost of which may be included in the Operating Expenses. Landlord shall not be obligated to maintain or repair any interior windows, doors, plate glass, the surfaces of walls or other fixtures, components or equipment within the Premises (other than components of Core Building Systems that do not exclusively serve the Premises), but the same shall be Tenant’s obligation. Tenant shall promptly report in writing to Landlord any defective condition known to it that Landlord is required to repair. Tenant waives the benefit of any present or future law that provides Tenant the right to repair the Premises or Property at Landlord’s expense or to terminate this Lease because of the condition of the Property or Premises, Notwithstanding the fact that Landlord may elect, at Landlord’s sole discretion, to provide security services at the Property or Building at any time during the Term of this Lease, then to the maximum extent this agreement may be made effective according to law (including the limitations set forth in M.G.L. c. 186, §15), but subject to Tenant’s insurance requirements hereunder and Section 7.03 (i) Tenant hereby releases Landlord from any claim for injury to person or damage to property asserted by Tenant or any personnel, employee, guest, invitee or agent of Tenant that is suffered or occurs in or about the Premises or in or about the Building or Property or the common areas appurtenant thereto by reason of the act of any intruder or any other person in or about the Premises, Building or Property, and (ii) Landlord shall not be deemed to owe Tenant, or any person claiming by, through or under Tenant, any duty or standard of care as a result of Landlord’s provision of such security services.

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10.04.    Tenant’s Obligations.

(a)    Repair and Maintenance. Except for work that Section 10.03 or Article 12 requires Landlord to do, Tenant at its sole cost and expense shall keep the Premises including, without limitation, all Initial Tenant Improvements, other Tenant Work, Tenant Property, fixtures, systems and equipment now or hereafter on the Premises, or elsewhere exclusively serving the Premises, in good order, condition and repair, reasonable wear and tear, and damage by casualty or taking (to the extent provided in Article 12 only), excepted; shall keep in a safe, secure and sanitary condition all trash and rubbish temporarily stored at the Premises; and shall make all repairs and replacements and to do all other work necessary for the foregoing purposes whether the same may be ordinary or extraordinary, foreseen or unforeseen. The foregoing shall include, without limitation, Tenant’s obligation to maintain floors and floor coverings, to paint and repair walls and doors, to replace and repair all interior glass and windows, ceiling tiles, lights and light fixtures, pipes, drains and the like in the Premises. Tenant shall hire its own cleaning contractor for the Premises and shall provide first- class janitorial service in the Premises on each business day during the Term (including daily disposal of trash from trash bins in the Premises). If applicable, Tenant shall arrange for disposal of its own lab-related refuse and/or hazardous waste by a licensed vendor in accordance with all applicable Legal Requirements and Section 9.04 hereof. No storage shall be permitted outside of the Premises. Storage inside the Premises shall be provided in a manner not visible from outside the Premises. (For purposes of this Section, the term “reasonable wear and tear” constitutes that normal, gradual deterioration that occurs due to aging and ordinary use despite reasonable and timely maintenance and repairs or repairs and restoration, as the case may be; in no event shall “reasonable wear and tear” excuse Tenant from its obligations duty to maintain and/or repair as may be required hereunder.)

(b)    Landlord’s Right to Cure. If Tenant does not perform any of its obligations under Section 10.04(a), Landlord upon ten (10) days’ prior notice to Tenant (or without prior notice in the case of emergency) may perform such maintenance, repair or replacement on Tenant’s behalf, and Tenant shall reimburse Landlord for all costs reasonably incurred together with an Administrative Charge (as defined in Section 14.02(f)), immediately upon demand.

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10.05.    Tenant Work.

(a)    General. “Tenant Work” shall mean all work including demolition, improvements, additions and alterations in or to the Premises, including the Initial Tenant Improvements. Without limitation, Tenant Work includes any penetrations in the walls, partitions, ceilings or floors and all attached carpeting, all signs visible from the exterior of the Premises, and any change in the exterior appearance of the windows in the Premises (including shades, curtains and the like). All Tenant Work shall be subject to Landlord’s prior written approval, which approval Landlord agrees not unreasonably to withhold, condition or delay as to nonstructural aspects of Tenant’s Work (nonstructural aspects being those that do not adversely affect the Building’s structure, roof, exterior or mechanical, electrical, plumbing, life safety or other Building systems or architectural design, character or use of the Premises or the Building) and shall be arranged and paid for by Tenant all as provided herein; provided that any interior, non-structural Tenant Work (including any series of related Tenant Work projects) that (a) costs less than the “Tenant Work Threshold Amount” (which shall be $25, 000.00), (b) does not affect, except to a de minimis extent, any fire-safety, telecommunications, electrical, mechanical, ventilation or plumbing systems of the Building (“Core Building Systems”), and (c) does not affect any penetrations in or otherwise affect any walls (except, as to non-structural walls, to a de minimis extent), floors, roofs, or other structural elements of the Building or any signs visible from the exterior of the Premises or any change in the exterior appearance of the windows in the Premises (including shades, curtains and the like) shall not require Landlord’s prior approval if Tenant delivers the Construction Documents (as defined in Section 10.05(b)) for such work to Landlord at least five (5) business days’ prior to commencing such work along with notice including the name and contact information for the contractor(s) performing work in connection therewith, required evidence of insurance and such other reasonable information as Landlord may reasonably require, if any). Whether or not Landlord’s approval is required, Tenant shall neither propose nor effect any Tenant Work that in Landlord’s reasonable judgment (i) adversely affects any structural component of the Building, (ii) would be incompatible with the Core Building Systems, (iii) affects the exterior or the exterior appearance of the Building or common areas within or around the Building or other property than the Premises, (iv) diminishes the value of the Premises, or (v) requires any unusual expense to readapt the Premises. Prior to commencing any Tenant Work affecting air disbursement from ventilation systems serving Tenant or the Building, including, without limitation, the installation of Tenant’s exhaust systems, Tenant shall provide Landlord with a third party report from a consultant, and in a form, reasonably acceptable to Landlord, showing that such work will not adversely affect the ventilation systems of the Building (or of any other tenant in the Building) and shall, upon completion of such work, provide Landlord with a certification reasonably satisfactory to Landlord from such consultant confirming that no such adverse effects have resulted from such work. If, as a result of any Tenant Work, Landlord is obligated to comply with any Legal Requirement, including, but not limited to, the Americans With Disabilities Act, and such compliance requires Landlord to make any improvement or alteration to any portion of the Property, as a condition to Landlord’s consent, Landlord shall have the right to require Tenant to pay to Landlord prior to the construction of any improvement or alteration by Tenant, as Additional Rent, the entire cost of any improvement or alteration Landlord is obligated to complete by such law or regulation.

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(b)    Construction Documents. No Tenant Work which is of a nature typically requiring construction drawings and specifications or requires a building permit shall be effected except in accordance with complete, coordinated construction drawings and specifications (“Construction Documents”) prepared in accordance with Exhibit F. Before commencing any Tenant Work requiring Landlord’s approval hereunder, Tenant shall obtain Landlord’s prior written approval of the Construction Documents for such work, which approval shall not be unreasonably withheld or delayed. The Construction Documents shall be prepared by an architect (“Tenant’s Architect”) registered in the Commonwealth of Massachusetts experienced in the construction of tenant space improvements in comparable buildings in the area where the Premises are located and, if the value of such Tenant Work will equal or exceed the Tenant Work Threshold Amount or will affect any Core Building Systems or structural components of the Building, the identity of such Architect shall be approved by Landlord in advance, such approval not to be unreasonably withheld in the case of interior, non-structural Tenant Work. Tenant shall be solely responsible for the liabilities associated with and expenses of all architectural and engineering services relating to Tenant Work and for the adequacy, accuracy, and completeness of the Construction Documents even if approved by Landlord (and even if Tenant’s Architect has been otherwise engaged by Landlord in connection with the Building). The Construction Documents shall set forth in detail the requirements for construction of the Tenant Work and shall show all work necessary to complete the Tenant Work including all cutting, fitting, and patching and all connections to the mechanical, electrical, and plumbing systems and components of the Building. Submission of the Construction Documents to Landlord for approval shall be deemed a warranty by Tenant that all Tenant Work described in the Construction Documents (i) complies with all applicable laws, regulations, building codes, and highest design standards, (ii) does not adversely affect any structural component of the Building, (iii) is compatible with and does not adversely affect the Core Building Systems, (iv) does not affect any property other than the Premises, (v) conforms to floor loading limits specified by Landlord, and (vi) with respect to all materials, equipment and special designs, processes or products, does not infringe on any patent or other proprietary rights of others. The Construction Documents shall comply with Landlord’s requirements for the uniform exterior appearance of the Building, including, without limitation, the use of Building standard window blinds and Building standard light fixtures within fifteen (15) feet of each exterior window. Landlord’s approval of Construction Documents shall signify only Landlord’s consent to the Tenant Work shown and shall not result in any responsibility or warranty of Landlord concerning compliance of the Tenant Work with laws, regulations, or codes, or coordination or compatibility with any component or system of the Building, or the feasibility of constructing the Tenant Work without damage or harm to the Building, all of which shall be the sole responsibility of Tenant.

(c)    Performance. The identity of any person or entity (including any employee or agent of Tenant) performing or designing any Tenant Work (“Tenant Contractor”) shall, if the cost of such work in any instance is in excess of the Tenant Work Threshold Amount or will affect any Core Building Systems or structural components of the Building or involves any work other than interior, nonstructural alterations, be approved in advance by Landlord, such approval not to be unreasonably withheld. Once any Tenant Contractor has been approved, then the same Tenant Contractor may thereafter be used by Tenant for the same type of work until Landlord notifies Tenant that such Tenant Contractor is no longer approved. Tenant shall procure at Tenant’s expense all necessary permits and licenses before undertaking any Tenant Work but shall not take any plans for Tenant Work to the municipal inspection services or fire departments, without on each occasion obtaining Landlord’s prior written consent. Tenant shall perform all Tenant Work at Tenant’s risk in compliance with all applicable laws and the rules and regulations for Tenant Work attached hereto as Exhibit C as the same may be reasonably amended by Landlord from time to time and in a good and workmanlike manner employing new materials of good quality and producing a result at least equal in quality to the other parts of the Premises. When any Tenant Work is in progress, Tenant shall cause to be maintained insurance as described in the Tenant Work Insurance Schedule attached as Exhibit D and such other insurance as may be required under this Lease or reasonably required by Landlord covering any additional hazards due to such Tenant Work, and, if the cost of such Tenant Work exceeds the Tenant Work Threshold Amount also such bonds or other assurances of satisfactory completion and payment as Landlord may reasonably require, in each case for the benefit of Landlord. If the Tenant Work in any instance requires Landlord’s approval hereunder, Tenant shall reimburse Landlord for its reasonable costs of reviewing the proposed Tenant Work and inspecting installation of the same. At all times while performing Tenant Work, Tenant shall require any Tenant Contractor to comply with all applicable laws, regulations, permits and Landlord’s rules and regulations relating to such work, including, without limitation, use of loading areas, elevators and lobbies. Landlord shall have the right to stop any work not being performed in conformance with this Lease, and, at its option, may repair or remove non-conforming work at the expense of Tenant. Each Tenant Contractor working on the roof of the Building shall coordinate with Landlord’s roofing contractor, shall comply with its requirements and shall not violate existing roof warranties. Each Tenant Contractor shall work on the Premises without causing labor disharmony, coordination difficulties, or delay to or impairing of any guaranties, warranties or the work of any other contractor. Tenant shall obtain from each Tenant Contractor, prior to entry into the Building, an agreement to indemnify and hold the Indemnitees harmless from any claim, loss or expense arising in whole or in part out of any act or neglect committed by or under such person while on or about the Premises or Building to the same extent as Tenant has so agreed in this Lease, the indemnities of Tenant and Tenant Contractor being joint and several.

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(d)    Payment. Tenant shall pay the entire cost of all Tenant Work so that the Premises, including Tenant’s leasehold, shall always be free of liens for labor or materials. If any such lien is filed that is claimed to be attributable to Tenant or persons acting under Tenant, then Tenant shall promptly (and always within thirty (30) days of Tenant’s notice of filing thereof) discharge the same.

(e)    Other. (i) Tenant must schedule and coordinate all aspects of work with the Building manager and Building engineer and shall make prior arrangements for elevator use with the Building manager. If an operating engineer is required by any union regulations, Tenant shall pay for such engineer. If shutdown of risers and mains for electrical, mechanical and plumbing work is required, such work shall be supervised by Landlord’s representative at Tenant’s cost. If special security arrangements must be made (e.g., in connection with work outside normal business hours), Tenant Contractor shall pay the actual cost of such security. No work shall be performed in Building mechanical or electrical equipment rooms without Landlord’s approval, which approval shall not be unreasonably withheld or delayed, and all such work shall be performed under Landlord’s supervision. Except in case of emergency, at least forty-eight (48) hours’ prior notice must be given to the Building management office prior to the shutdown of fire, sprinkler and other alarm systems, and in case of emergency, prompt notice shall be given. In the event that such work unintentionally alerts the Fire or Police Department or any private alarm monitoring company through an alarm signal, Tenant shall be liable for any fees or charges levied in connection with such alarm. Tenant shall pay to Landlord such charges as may from time to time be in effect with respect to any such shutdown. All demolition, installations, removals or other work that is reasonably likely to inconvenience other tenants or disturb Building operations must be scheduled with the Building manager at least twenty-four (24) hours in advance.

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(ii)    Tenant shall take all necessary and appropriate steps to ensure that any work carried out by or on behalf of Tenant is done in a manner so as to not interfere with any other tenants or occupants of the Building, except to a de minimis extent. Installations within the Premises (and elsewhere where Tenant is permitted to make installations) shall not interfere with existing services and shall be installed so as not to unreasonably interfere with subsequent installation of ceilings or services for other tenants. Redundant electrical, control and alarm systems and mechanical equipment and sheet metal used or placed on the Property during construction and not maintained as part of Tenant5 s use of the Premises must be removed as part of the work.

(iii)    Each Tenant Contractor shall take all reasonable steps to assure that any work is carried out without disruption from labor disputes arising from whatever cause, including disputes concerning union jurisdiction and the affiliation of workers employed by said Tenant Contractor or its subcontractors. Tenant shall be responsible for, and shall reimburse Landlord for, all actual costs and expenses, including reasonable attorneys’ fees incurred by Landlord in connection with the breach by any Tenant Contractor of such obligations. If Tenant does not promptly resolve any labor dispute caused by or relating to any Tenant Contractor, Landlord may in its sole discretion request that Tenant remove such Tenant Contractor from the Property, and if such Tenant Contractor is not promptly removed, Landlord may prohibit such Tenant Contractor from entering the Property.

(iv)    Tenant shall diligently pursue and complete all Tenant Work and upon completion thereof, Tenant shall give to Landlord (x) a permanent certificate of occupancy (if one is legally required) and any other final governmental approvals required for such work, (y) copies of “as built” plans and all construction contracts and (z) proof of payment for all labor and materials.

10.06.    Condition upon Termination. At the expiration or earlier termination of the Term, Tenant (and all persons claiming through Tenant) shall without the necessity of notice, deliver the Premises (including all Initial Tenant Improvements and Tenant Work, and all replacements thereof, except such additions, alterations, Initial Tenant Improvements and other Tenant Work as the Landlord may direct to be removed at the time the Landlord approves the plans thereof, or, in the case of Tenant Work not subject to Landlord approval, at the time of expiration or earlier termination of the Term) broom-clean, in compliance with the requirements of Section 10.07 and in good and tenantable condition, reasonable wear and tear, and damage by casualty or taking (to the extent provided in Article 12 only) excepted. (For purposes of the foregoing sentence, the term “reasonable wear and tear” constitutes that normal, gradual deterioration that occurs due to aging and ordinary use despite reasonable and timely maintenance and repairs; in no event shall “reasonable wear and tear” excuse Tenant from its duty to maintain same in good condition and repair and otherwise serviceable.) The Premises shall be surrendered to Landlord free and clear of any mechanic’s liens (or any similar lien related to labor or materials) filed against any part of the Premises and free and clear of any financing or other encumbrance on any equipment and/or Initial Tenant Improvements or Tenant Work to be surrendered with the Premises. As part of such delivery, Tenant shall also provide all keys (or lock combinations, codes or electronic passes) to the Premises to Landlord; remove all signs wherever located; and, except as provided in this Section 10.06, remove all Tenant Property whether or not bolted or otherwise attached. As used herein, “Tenant Property” shall mean all trade fixtures, furnishings, equipment inventory, cabling and other personal property owned by Tenant or any person acting under Tenant at the Premises. Tenant shall repair all damage that results from such removal and restore the Premises substantially to a fully functional and tenantable condition (including the filling of all floor and wall holes, the removal of all disconnected wiring back to junction boxes and the replacement of all damaged ceiling tiles). Any property not so removed shall be deemed abandoned, shall at once become the property of Landlord, and may be disposed of in such manner as Landlord shall see fit; and Tenant shall pay the cost of removal and disposal to Landlord upon demand. The covenants of this Section shall survive the expiration or earlier termination of the Term.

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10.07.    Decommissioning of the Premises. Prior to the expiration of this Lease (or within thirty (30) days after any earlier termination), Tenant shall clean and otherwise decommission all interior surfaces (including floors, walls, ceilings, and counters), piping, supply lines, waste lines and plumbing in and/or exclusively serving the Premises, and all exhaust or other ductwork in and/or exclusively serving the Premises, in each case which has carried or released or been exposed to any Environmental Substances, and shall otherwise clean the Premises so as to permit the report hereinafter called for by this Section 10.07 to be issued. Prior to the expiration of this Lease (or within thirty (30) days after any earlier termination), Tenant, at Tenant’s expense, shall obtain for Landlord a report addressed to Landlord and Landlord’s designees (and, at Tenant’s election, Tenant) by a reputable licensed environmental engineer that is designated by Tenant and acceptable to Landlord in Landlord’s reasonable discretion, which report shall be based on the environmental engineer’s inspection of the Premises and shall show: that the Environmental Substances, to the extent, if any, existing prior to such decommissioning, have been removed as necessary so that the interior surfaces of the Premises (including floors, walls, ceilings, and counters), piping, supply lines, waste lines and plumbing, and all such exhaust or other ductwork in and/or exclusively serving the Premises, may be reused by a subsequent tenant or disposed of in compliance with applicable Environmental Laws (as defined in Section 9.04 hereof) without taking any special precautions for Environmental Substances, without incurring special costs or undertaking special procedures for demolition, disposal, investigation, assessment, cleaning or removal of Environmental Substances and without incurring regulatory compliance requirements or giving notice in connection with Environmental Substances; and that the Premises may be reoccupied for office or laboratory use, demolished or renovated without taking any special precautions for Environmental Substances, without incurring special costs or undertaking special procedures for disposal, investigation, assessment, cleaning or removal of Environmental Substances and without incurring regulatory requirements or giving notice in connection with Environmental Substances. Further, for purposes of this Section: “special costs” or “special procedures” shall mean costs or procedures, as the case may be, that would not be incurred but for the nature of the Environmental Substances as Environmental Substances instead of non-hazardous materials. The report shall include reasonable detail concerning the clean-up location, the tests run and the analytic results. If Tenant fails to perform its obligations under this Section, without limiting any other right or remedy, Landlord may, on ten (10) business days’ prior written notice to Tenant perform such obligations at Tenant’s expense, and Tenant shall promptly reimburse Landlord upon demand for all costs and expenses reasonably incurred together with an Administrative Charge, as defined in Section 14.02(f). Tenant’s obligations under this Section shall survive the expiration or earlier termination of this Lease.

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ARTICLE 11: INITIAL TENANT IMPROVEMENTS

11.01.    Tenant has provided Landlord with all necessary information regarding Tenant’s space planning needs in connection with its use of the Premises. Based upon such information supplied by Tenant, space plans and specifications have been prepared (the “Plans and Specifications”) for the layout of Tenant’s leasehold improvements to the Premises (“Initial Tenant Improvements”), The Initial Tenant Improvements shall not include Tenant’s furniture, trade fixtures, equipment and personal property and are limited to the fit-up construction, as generally laid out and specified on the Plans and Specifications, Tenant acknowledges that the Initial Tenant Improvements, except as expressly provided in the Plans and Specifications, will be substantially designed and constructed to the general quality of the design and construction of the Building and in accordance with Landlord’s building standards for the Building. Tenant has approved and agreed to the Plans and Specifications. The Plans and Specifications are attached hereto as Exhibit H.

11.02.    Tenant agrees that Landlord shall have no obligation to make any material changes to the Plans and Specifications requested by Tenant, provided, however, to the extent Landlord agrees to any changes whether material or immaterial, Tenant agrees that any additional actual cost to Landlord, in excess of the Improvement Allowance and the Additional Allowance, if applicable, resulting from such approved changes shall be the responsibility of Tenant and shall be paid in full by Tenant to Landlord within ten (10) business days of billing therefor by Landlord; and Tenant agrees that if any such changes do result in delay in Substantial Completion, same shall be deemed a Tenant Delay (as defined below).

11.03.    Landlord shall proceed, using reasonable efforts, to obtain all necessary permits and approvals for the construction of the Initial Tenant Improvements, to engage a contractor or construction manager to perform or supervise the construction and to proceed to construct the Initial Tenant Improvements in substantial conformance with the Plans and Specifications. Landlord reserves the right to make changes and substitutions to the Plans and Specifications in connection with the construction of the Initial Tenant Improvements, provided same do not materially adversely modify the Plans and Specifications or the schedule or delivery of the Initial Tenant Improvements. Landlord agrees to use reasonable efforts to Substantially Complete the Initial Tenant Improvements in a good and workmanlike manner by the Anticipated Term Commencement Date, but in no event shall Landlord be liable to Tenant for any failure to deliver the Premises on any specified date, nor shall such failure give rise to any default or other remedies under this Lease or at law or equity; provided, however, in the event Landlord has failed to Substantially Complete the Initial Tenant Improvements on or before the date that is sixty (60) days after the Anticipated Term Commencement Date (as such date shall be extended due to Tenant Delay (as defined herein) or Force Majeure), then Tenant shall be entitled to a credit against Base Rent first due under the Lease in an amount equal to one day of Base Rent for each day after such sixtieth (60th) day until the Initial Tenant Improvements is Substantially Complete. Such rent credit shall be applied against the Base Rent obligations beginning on the Term Commencement Date until such credit has been exhausted.

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11.04.    Tenant’s Improvements shall be deemed “Substantially Complete” on the date (the “Substantial Completion Date”) Tenant receives notice from Landlord that Landlord has received a certificate of occupancy (temporary or permanent) or a fully-signed off building permit for the Premises issued by the Town of Lexington (the “Certificate of Occupancy”). Any of the Initial Tenant Improvements not fully completed (of which Tenant shall give Landlord notice as provided below) on the Term Commencement Date shall thereafter be so completed with reasonable diligence by Landlord. Notwithstanding the foregoing, if any delay in the Substantial Completion of the Initial Tenant Improvements by Landlord is due to Tenant Delays, then the Substantial Completion Date shall be deemed to be the date (as set forth in a written notice from Landlord to Tenant) the Initial Tenant Improvements would have been Substantially Complete, if not for such Tenant Delays, as reasonably determined by Landlord. “Tenant Delays”, shall mean delays caused by: (i) requirements of the Plans and Specifications requested by Tenant that do not conform to Landlord’s building standards for office build-out, or which contain long lead-time or non-standard items requested by Tenant; (ii) any material change in the Plans and Specifications requested by Tenant and agreed to by Landlord; (iii) any request by Tenant for a delay in the commencement or completion of the Initial Tenant Improvements for any reason; or (iv) any other act or omission of Tenant or its employees, agents or contractors which reasonably inhibits the Landlord from timely completing the Initial Tenant Improvements. The Premises shall not be deemed to be unavailable if only minor or insubstantial details of construction, decoration or mechanical adjustments remain to be done. If as a result of Tenant Delays the Premises are deemed ready for Tenant’s occupancy, pursuant to the foregoing (and the term shall have commenced by reason thereof), but the Premises are not in fact actually ready for Tenant’s occupancy, Tenant shall not (except with Landlord’s consent not to be unreasonably withheld, conditioned or delayed) be entitled to take possession of the Premises for the permitted use until the premises are in fact actually ready for such occupancy.

11.05.    Within seven (7) business days after the Term Commencement Date, Landlord and Tenant shall confer and create a specific list of any defects or incomplete remaining items of work with respect to the Initial Tenant Improvements (a “Punchlist”). Except with respect to the items contained in the Punchlist, Tenant shall be deemed satisfied with the Initial Tenant Improvements, Landlord shall be deemed to have completed all of its obligations under this Article 11 and Tenant shall have no claim that Landlord has failed to perform in full its obligations hereunder.

11.06.    This Lease is subject to the Landlord obtaining all permits, licenses and approvals necessary to allow Landlord to construct the Initial Tenant Improvements and obtain a Certificate of Occupancy with respect thereto; and if despite Landlord’s good faith efforts Landlord shall be unable to obtain such permits, license, approvals, or Certificate of Occupancy, and is therefore unable to commence or complete the Initial Tenant Improvements, then this lease may be terminated by Landlord by written notice to Tenant.

11.07.    If Tenant occupies the Premises prior to the Term Commencement Date (which shall only be allowed upon the prior written consent of the Landlord), such occupancy shall be subject to all provisions of this Lease, such occupancy shall not change the Termination Date, and Tenant shall pay rent and all other charges provided for in this Lease during the period of such occupancy. Tenant shall be liable for any damages or delays caused by Tenant’s activities at the Premises. Prior to entering the Premises, Tenant shall obtain all insurance it is required to obtain by the Lease and shall provide certificates of said insurance to Landlord. Tenant shall coordinate such entry with Landlord’s building manager, and such entry shall be made in compliance with all terms and conditions of this Lease and the rules and regulations in effect from time to time.

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11.08.    Landlord shall pay the costs and expenses incurred by Landlord in connection with the performance and completion of the Initial Tenant Improvements in an amount not to exceed $372, 100.00 (based on $50.00 multiplied by 7, 442 rentable square feet of the Premises) (the “Improvement Allowance”) and this shall be Landlord’s maximum contribution to the cost of constructing and installing the Initial Tenant Improvements. Landlord may include within the Improvement Allowance all reasonable, costs and expenses incurred by or on behalf of Landlord in connection with the Initial Tenant Improvements including without limitation, all design, review, permitting, bid preparation and bid review, construction, materials and supplies, and including a construction or project management fee payable to Landlord of three percent (3%) of the costs of the Initial Tenant Improvements. Landlord shall have no separate or additional obligation to pay Tenant the Improvement Allowance. Tenant shall be responsible for and promptly (but in no event longer than ten (10) days after request therefor) pay directly or pay to Landlord for, as appropriate, and indemnify and reimburse Landlord from and against, any actual costs of the Initial Tenant Improvements that are in excess of the Improvement Allowance including, without limitation, such costs over and above the Improvement Allowance necessary to complete the Initial Tenant Improvements as set forth in the Plans and Specifications, costs resulting from the Tenant’s upgrades from building standard construction materials or Tenant’s upgrades or changes to the Initial Tenant Improvements or any plans or specifications relating thereto. Landlord shall have the same rights and remedies which Landlord has upon the nonpayment of Base Rent and other charges due under this Lease for nonpayment of any amounts which Tenant is required to pay to Landlord or Landlord’s contractor in connection with the Initial Tenant Improvements or in connection with any construction in the Premises performed for Tenant by Landlord, Landlord’s contractor or any other person, firm or entity after the Term Commencement Date. Except for the Initial Tenant Improvements and any repairs expressly required to be made by Landlord under this Lease, Landlord shall have no obligation to perform any work or construction to make the premises fit for use and occupation or for Tenant’s particular purpose or to make them acceptable to Tenant.

11.09.    Additional Improvement Allowance. In addition to the Tenant Improvement Allowance, upon the full use of the Tenant Improvement Allowance as provided herein, Landlord will make available to Tenant an additional allowance in an amount not to exceed $148, 840.00 (based on $20.00 multiplied by 7, 442 rentable square feet of the Premises) (the “Additional Improvement Allowance”), subject to repayment with interest as provided herein. The Additional Improvement Allowance shall be utilized for the same purposes of the Improvement Allowance and paid (and repaid) as provided below pursuant to the terms and conditions hereof. Notwithstanding anything to the contrary set forth in this Lease, all amounts disbursed or advanced under the Additional Improvement Allowance shall (together with interest as set forth below) be repaid to Landlord as Additional Rent on the following terms and conditions follows:

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(a)    Interest on the principal balance of the Additional Improvement Allowance from time to time outstanding shall accrue from the Commencement Date at the rate of eight percent (8%) per year. Interest shall be calculated on the basis of a 360-day year times the actual number of days elapsed.

(b)    Until the first (1st) day of the month following the month in which the Term Commencement Date shall have occurred (the “Conversion Date”), interest only on the principal balance of the Additional Improvement Allowance shall be payable monthly in arrears on the first (1st) day of each month.

(c)    From and after the Conversion Date, principal and interest on the principal balance of the Additional Improvement Allowance shall be payable, as Additional Rent, in arrears on the first (1st) day of each month in equal monthly installments and in a manner such that the entire principal and interest shall be paid by no later than the last day of the Initial Term.

(d)    Tenant may prepay the outstanding balance of the Additional Improvement Allowance, in whole or in part, and any accrued interest thereon, at any time, without premium or penalty.

11.10.    All components of the Initial Tenant Improvements shall be part of the Building, except only for such items as Landlord shall designate in writing to be removed by Tenant on the termination of this Lease, which notice shall be delivered to Tenant simultaneously with the approval of the Plans and Specifications.

ARTICLE 12: DAMAGE OR DESTRUCTION; CONDEMNATION

12.01.    Damage or Destruction of Premises.

12.01.01    If the Premises or any part thereof shall be damaged by fire or other insured casualty, then, subject to Subsection 12.01.2, Landlord shall proceed with diligence, subject to then applicable statutes, building codes, zoning ordinances and regulations of any governmental authority, and at the expense of Landlord (but only to the extent of insurance proceeds made available to Landlord by any mortgagee of the Building and any ground lessor) to repair or cause to be repaired such damage (other than any Initial Tenant Improvements and Tenant Work, which Tenant shall promptly commence, and proceed with diligence, to restore, but only to the extent of insurance proceeds (plus commercially reasonable deductible(s)) so long as Tenant was carrying the insurance coverages required in this Lease). All such repairs made necessary by any act or omission of Tenant shall be made at the Tenant’s expense to the extent that the cost of such repairs are less than the deductible amount in Landlord’s insurance policy. All repairs to and replacements of Tenant Property and any Initial Tenant Improvements and Tenant Work shall be made by and at the expense of Tenant. The cost of any repairs performed under this Section by Landlord at Tenant’s expense (including costs of design fees, financing, and charges for administration, overhead and construction management services by Landlord and Landlord’s contractor) shall constitute Additional Rent hereunder. If the Premises or any part thereof shall have been rendered unfit for use and occupation hereunder by reason of such damage, the Base Rent or a just and proportionate part thereof, according to the nature and extent to which the Premises shall have been so rendered unfit, shall be abated until the Premises (except as to Tenant Property, Initial Tenant Improvements and any Tenant Work) shall have been restored as nearly as practicable to the condition in which they were immediately prior to such fire or other casualty. Landlord shall not be liable for delays in the making of any such repairs that are due to government regulation, casualties, and strikes, unavailability of labor and materials, delays in obtaining insurance proceeds, and other causes beyond the reasonable control of Landlord, nor shall Landlord be liable for any inconvenience or annoyance to Tenant or injury to the business of Tenant resulting from delays in repairing such damage.

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12.01.2    If (i) the Premises are so damaged by fire or other casualty (whether or not insured) at any time during the last thirty (30) months of the Term that the cost to repair such damage is reasonably estimated to exceed one-third (1/3) of the total Base Rent payable hereunder for the period from the estimated completion date of repair until the end of the Term, (ii) at any time the Building (or any portion thereof, whether or not including any portion of the Premises) is so damaged by fire or other casualty (whether or not insured) that substantial alteration or reconstruction or demolition of the Building (or a portion thereof) shall in Landlord’s good faith judgment be required, or (iii) at any time damage to the Building occurs by fire or other insured casualty and any mortgagee or ground lessor shall refuse to permit insurance proceeds to be utilized for the repair or replacement of such property and Landlord determines not to repair such damage, then and in any of such events, this Lease and the term hereof may be terminated at the election of Landlord by a notice from Landlord to Tenant within ninety (90) days, or such longer period, but in any event not to exceed one hundred twenty (120) days as is required to complete arrangements with any mortgagee or ground lessor regarding such situation, following such fire or other casualty; the effective termination date pursuant to such notice shall be not less than thirty (30) days after the day on which such termination notice is received by Tenant. If any mortgagee refuses without fault by Tenant to permit insurance proceeds to be applied to replacement of the Premises, and neither Landlord nor such mortgagee has commenced such replacement within six (6) months following adjustment of such casualty loss with the insurer, then Tenant may, until any such replacement commences, terminate this Lease by giving at least thirty (30) days prior written notice thereof to Landlord and such termination shall be effective on the date specified if such replacement has not then commenced. In addition, if a substantial portion of the Premises is damaged by fire or other casualty or Tenant’s access to the Premises is denied by reason of damage by fire or other casualty to such extent that Landlord fails to complete the repairs required hereunder within seven (7) months after the occurrence thereof, Tenant, upon sixty (60) days’ written notice to Landlord, may terminate this Lease; provided, however, that if Landlord completes said repairs prior to the end of said sixty (60) day period, Tenant’s notice shall be void and this Lease shall continue in full force and effect. In the event of any termination, the Term shall expire as though such effective termination date were the date originally stipulated in Article 1 for the end of the Term and the Base Rent and Additional Rent for Total Operating Costs (to the extent not abated as set forth above) shall be apportioned as of such date.

12.02.    Eminent Domain. In the event that all or any substantial part of the Premises or the Building or its common areas is taken (other than for temporary use, hereafter described) by public authority under power of eminent domain (or by conveyance in lieu thereof), then by notice given within three (3) months following the recording of such taking (or conveyance) in the appropriate registry of deeds, this Lease may be terminated at Landlord’s election, or Tenant’s election if such taking shall prevent Tenant from using at least fifty percent (50%) of the Premises for their intended purposes, thirty (30) days after such notice, and Base Rent and Tenant’s share of Total Operating Costs and Taxes shall be apportioned as of the date of termination. If this Lease is not terminated as aforesaid, subject to the rights of mortgagees Landlord shall within a reasonable time thereafter, diligently restore what may remain of the Premises (excluding any Tenant Property or other items installed or paid for by Tenant that Tenant is permitted or may be required to remove upon expiration and any Initial Tenant Improvements and Tenant Work) to a tenantable condition. In the event some portion of rentable floor area of the Premises is taken (other than for temporary use) and this Lease is not terminated, Base Rent shall be proportionally abated for the remainder of the Term. In the event of any taking of the Premises or any part thereof for temporary use, (i) this Lease shall be and remain unaffected thereby and rent shall not abate, and (ii) Tenant shall be entitled to receive for itself such portion or portions of any award made for such use with respect to the period of the taking that is within the Term, provided that if such taking shall remain in force at the expiration or earlier termination of this Lease, then Tenant shall pay to Landlord a sum equal to the reasonable cost of performing Tenant’s obligations hereunder with respect to surrender of the Premises and upon such payment shall be excused from such obligations.

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So long as Tenant is not then in breach of any covenant or condition of this Lease beyond any applicable notice and cure periods, any specific damages that are expressly awarded to Tenant on account of its relocation expenses, and specifically so designated, shall belong to Tenant. Except as provided in the preceding sentence of this paragraph, Landlord reserves to itself, and Tenant releases and assigns to Landlord, all rights to damages accruing on account of any taking or by reason of any act of any public authority for which damages are payable. Tenant agrees to execute such further instruments of assignment as may be reasonably requested by Landlord, and to turn over to Landlord any damages that may be recovered in any proceeding or otherwise; and Tenant irrevocably appoints Landlord as its attorney-in-fact with full power of substitution so to execute and deliver in Tenant’s name, place and stead all such further instruments if Tenant shall fail to do so after ten (10) days’ notice.

ARTICLE 13: ASSIGNMENT AND SUBLETTING

13.01.    Landlord’s Consent Required. Except as set forth in this Article, Tenant shall not directly or indirectly assign this Lease, or sublet or license the Premises or any portion thereof, or advertise the Premises for assignment or subletting or permit the occupancy of all or any portion of the Premises by any person other than Tenant (each of the foregoing actions are collectively referred to as a “Transfer”) without obtaining, on each occasion, the prior written consent of Landlord, which consent shall not be unreasonably withheld, conditioned or delayed, and provided that Tenant complies with the provisions of this Article. A Transfer shall include, without limitation, any transfer of Tenant’s interest in this Lease by operation of law, merger or consolidation of Tenant into any other firm or corporation, and the transfer or sale of a controlling interest in Tenant, whether by sale of its capital stock or otherwise or any sale of all or a substantial part of Tenant’s assets. Any Transfer shall be subject to this Lease, all of the provisions of which shall be conditions to such Transfer and be binding on any transferee. No transferee shall have any right further to transfer its interest in the Premises, and nothing herein shall impose any obligation on Landlord with respect to a further Transfer. The foregoing restrictions shall be binding on any assignee or sublessee to which Landlord has consented, provided, notwithstanding anything else contained in this Lease, Landlord’s consent to any further assignment, subleasing or any sub-subleasing by any approved assignee or sublessee may be withheld by Landlord at Landlord’s sole discretion. If Tenant does Transfer with (or without) Landlord’s consent, any option or other right that Tenant may have relating to the Premises, including any right to extend the Term or lease other premises, shall automatically be terminated. Landlord’s Managing Agent (or such other manager of the Building appointed from time to time by Landlord) shall be Tenant’s exclusive broker for a period of six (6) months with respect to any proposed transfer so long as such Managing Agent uses its good faith best efforts to market in accordance with Tenant’s directions; and after such period Tenant may appoint a co-exclusive broker to serve along with Landlord’s Managing Agent Such Managing Agent shall be paid a brokerage fee for any transfer in accordance with such Managing Agent’s commission schedule then in effect so long as such schedule is competitive with similar schedules of major Greater Boston brokerage firms.

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13.02.    Terms. Without limitation, it shall not be unreasonable for Landlord to withhold such consent for any Transfer where, in Landlord’s reasonable opinion: (i) the proposed transferee does not have a financial standing and credit rating reasonably acceptable to Landlord; (ii) the proposed transferee is known to have a bad reputation in the business community; (iii) the business in which the proposed transferee is engaged could detract from, or be inappropriate for, the Building, its value or the costs of ownership thereof; (iv) Intentionally Omitted; (v) the proposed transferee is a current tenant or a prospective tenant (or any affiliate of such tenant or prospective tenant), meaning such tenant has been shown space or has been presented with or has made an offer to lease space, of the Building or the Project; (vi) the use of the Premises by any transferee (even though a Permitted Use) violates any use restriction granted by Landlord in any other lease or would otherwise cause Landlord to be in violation of its obligations under another lease or agreement to which Landlord is a party; (vii) if such Transfer is not approved of by the holder of any mortgage on the Property (if such approval is required); (viii) a proposed transferee’s business will impose a burden on the Property’s parking facilities, elevators, common areas, facilities, or utilities that is greater than the burden imposed by Tenant, in Landlord’s reasonable judgment; (ix) any guarantor (e.g., a subsequent assignor) of this Lease refuses to consent to the proposed transfer or to execute a written agreement reaffirming the guaranty; (x) Tenant is in default of any of its obligations under the Lease at the time of the request or at the time of the proposed Transfer; (xi) if requested by Landlord, the transferee refuses to sign a non-disturbance and attornment agreement in favor of Landlord’s lender; (xii) Landlord has sued or been sued by the proposed transferee or has otherwise been involved in a legal dispute with the proposed transferee; (xiii) the transferee is involved in a business which is not in keeping with the then current standards of the Property; (xiv) the Transfer will result in there being more than one subtenant of the Premises; or (xv) the transferee is a governmental or quasi- governmental entity or an agency, department or instrumentality of a governmental or quasi- governmental agency. Landlord may condition its consent upon such transferee depositing with Landlord such additional security as Landlord may reasonably require to assure the performance and observance of the obligations of such party to Landlord. In no event, however, shall Tenant assign this Lease or sublet the whole or any part of the Premises to a proposed transferee which has been judicially declared bankrupt or insolvent according to law, or with respect to which an assignment has been made of property for the benefit of creditors, or with respect to which a receiver, guardian, conservator, trustee in involuntary bankruptcy or similar officer has been appointed to take charge of all or any substantial part of the proposed transferee’s property by a court of competent jurisdiction, or with respect to which a petition has been filed for reorganization under any provisions of the Bankruptcy Code now or hereafter enacted, or if a proposed transferee has filed a petition for such reorganization, or for arrangements under any provisions of the Bankruptcy Code now or hereafter enacted and providing a plan for a debtor to settle, satisfy or extend the time for the payment of debts.

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13.03.    Right of Termination or Recapture. If Tenant requests Landlord’s consent to a Transfer (excepting a Related Party Transfer), an assignment of this Lease or a sublet of all or substantially all of the Premises for all or substantially all of the Term, Landlord shall have the option, exercisable by written notice to Tenant given within twenty (20) days after Landlord’s receipt of Tenant5s completed request, to terminate this Lease as of the date set forth by Landlord in such notice, which termination date must be no earlier than, and no later than thirty (30) days after, the proposed effective date of such requested assignment or subletting, as to the entire Premises in the case of a proposed Transfer of the whole Premises, and as to the portion of the Premises to be transferred in the case of a partial Transfer. In the event of termination in respect of a portion of the Premises, the portion so eliminated shall be delivered to Landlord on the date specified in good order and condition in the manner required under this Lease at the end of the Term and thereafter, to the extent necessary in Landlord’s judgment, Landlord, at Tenant’s cost and expense, may have access to and may make modification to the Premises (or portion thereof) so as to make such portion a self-contained rental unit with access to common areas, elevators and the like. Base Rent and the Tenant’s share shall be adjusted according to the extent of the rentable square footage of the Premises for which the Lease is terminated.

13.04.    Procedures. At least twenty (20) days prior to the effective date of any Transfer, Tenant shall give Landlord in writing the details of the proposed Transfer, including, but not limited to: (i) the name, business, and financial condition of the prospective transferee, (ii) a true and complete copy of the proposed instrument containing all of the terms and conditions of such Transfer, (iii) a written agreement of the assignee, subtenant or licensee agreeing with Landlord to perform and observe all of the terms, covenants, and conditions of this Lease undertaken by such transferee and such other matters as are contained in Landlord’s standard form of consent to a Transfer, and (iv) any other information Landlord reasonably deems relevant. Tenant shall pay to Landlord, as Additional Rent, Landlord’s reasonable attorneys’ fees in reviewing any Transfer. Tenant may make a Related Party Transfer (as defined below) without the consent of Landlord provided that Tenant gives Landlord at least ten (10) days’ prior notice thereof together with evidence reasonably satisfactory to Landlord that the proposed Transfer is a Related Party Transfer and such Related Party Transfer is subject to all of the other terms and conditions for this Article. A “Related Party Transfer” is a transfer to an entity (i) into or with which Tenant is merged or consolidated, (ii) to which substantially all of Tenant’s assets are transferred as a going concern, or (iii) which controls or is controlled by Tenant or is under common control with Tenant, provided that in any of such events (1) Landlord receives prior written notice of any such transactions, (2) the assignee or subtenant agrees directly with Landlord, by written instrument in form satisfactory to Landlord, to be bound by all the obligations of Tenant hereunder including, without limitation, the covenant against further assignment and subletting, (3) in no event shall Tenant be released from its obligations under this Lease, (4) any such transfer or transaction is for a legitimate, regular business purpose of Tenant other than a transfer of Tenant’s interest in this Lease, and (5) the involvement by Tenant or its assets in any transaction, or series of transactions (by way of merger, sale, acquisition, financing, refinancing, transfer, leveraged buy-out or otherwise) whether or not a formal assignment or hypothecation of this Lease or Tenant’s assets occurs, will not result in a reduction of the Net Worth of Tenant (as defined below), from the Net Worth of Tenant as it is represented to Landlord at the time of the execution by Landlord of this Lease, or as it exists immediately prior to said transaction or transactions constituting such reduction, at whichever time said Net Worth of Tenant was or is greater. “Net Worth” of Tenant for purposes of this Section shall be the tangible net worth of Tenant (excluding any guarantors) established under generally accepted accounting principles consistently applied.

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13.05.    Excess Rents. If the consideration, rent, or other amounts payable to Tenant under any other Transfer exceed the Rent and Tenant’s Transfer Expenses ((a) pro rated based on floor area in the case of a subletting, license or other occupancy of less than the entire area of the Premises and (b) amortized on a straight line basis over the remaining Term), then Tenant shall pay to Landlord, as Additional Rent, fifty percent (50%) of the amount of such excess when and as received. Tenant’s “Transfer Expenses” shall mean Tenant’s actual reasonable and necessary payments to third parties in connection with such a Transfer on account of brokerage, legal and market-based fit-up costs. Without limiting the generality of the first sentence of this Section, any lump-sum payment or series of payments (including, without limitation, for the purchase or use of so-called leasehold improvements or Tenant Property and any separate charges for services) on account of any Transfer shall be deemed to be in excess of Rent and other charges in its or their entirety.

13.06.    No Release. Notwithstanding any Transfer and whether or not the same is a Related Party Transfer or is consented to, the liability of Tenant to Landlord shall remain direct and primary. Any transferee of all or substantially all of Tenant’s interest in the Premises (including any such transferee under a Related Party Transfer) shall be jointly and severally liable with Tenant to Landlord for the performance of all of Tenant’s covenants under this Lease; and such assignee shall upon request execute and deliver such instruments as Landlord reasonably requests in confirmation thereof (and agrees that its failure to do so shall be a default). Tenant hereby irrevocably authorizes Landlord to collect Rent from any transferee (and upon notice any transferee shall pay directly to Landlord) and apply the net amount collected to the rent and other charges reserved under this Lease. No Transfer shall be deemed a waiver of the provisions of this Section, or the acceptance of the transferee as a tenant, or a release of Tenant from direct and primary liability for the performance of all of the covenants of this Lease. Notwithstanding anything to the contrary in the documents effecting the Transfer, no Transfer shall alter in any manner whatsoever the terms of this Lease, to which any Transfer at all times shall be subject and subordinate. The breach by Tenant or any transferee of any covenant in this Article shall be a default for which there is no cure period.

Anything contained in the foregoing provisions of this Section to the contrary notwithstanding, neither Tenant nor any transferee nor any other person having an interest in the possession, use, occupancy or utilization of the Premises shall enter into any lease, sublease, assignment, license, concession or other agreement for use, occupancy or utilization of space in the Premises that provides for rental or other payment for such use, occupancy or utilization based, in whole or in part, on the net income or profits derived by any person from the Premises leased, used, occupied or utilized (other than an amount based on a fixed percentage or percentages of receipts or sales), and any such purported lease, sublease, assignment, license, concession or other agreement shall be absolutely void and ineffective as a conveyance of any right or interest in the possession, use, occupancy or utilization of any part of the Premises.

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13.07.    Certain Additional Rights. If the Premises or any part thereof are Transferred by Tenant, following the occurrence of a default which has continued beyond any applicable cure period, Landlord, in addition to any other remedies provided hereunder or at law, may at its option collect directly from any such transferee(s) all rents becoming due to the Tenant under any such Transfer and apply such rent against any amounts due Landlord by Tenant under this Lease, and Tenant hereby irrevocably authorizes and directs such transferee(s) to so make all such rent payments, if so directed by Landlord; and it is understood that no such election or collection or payment shall be construed to constitute a novation of this Lease or a release of Tenant hereunder, or to create any lease or occupancy agreement between the Landlord and such subtenant or impose any obligations on Landlord, or otherwise constitute the recognition of such sublease by Landlord for any purpose whatsoever. Tenant hereby absolutely and unconditionally assigns and transfers to Landlord all of Tenant’s interest in all rentals and income arising from any Transfer entered into by Tenant, and Landlord may collect such rent and income and apply same toward Tenant’s obligations under this Lease; provided, however, that until a default occurs in the performance of Tenant’s obligations under this Lease, Tenant may receive, collect and enjoy the rents accruing under such Transfer. Landlord shall not, by reason of this or any other assignment of such rents to Landlord nor by reason of the collection of the rents from a transferee, be deemed to have assumed or recognized any Transfer or to be liable to the transferee for any failure of Tenant to perform and comply with any of Tenant’s obligations to such transferee under such Transfer, including, but not limited to, Tenant’s obligation to return any security deposit. Tenant hereby irrevocably authorizes and directs any such transferee, upon receipt of a written notice from Landlord stating that a default exists in the performance of Tenant’s obligations under this Lease, to pay to Landlord the rents due as they become due under the Transfer. Tenant agrees that such transferee shall have the right to rely upon any such statement and request from Landlord, and that such transferee shall pay such rents to Landlord without any obligation or right to inquire as to whether such default exists and notwithstanding any notice from or claim from Tenant to the contrary. In the event Tenant shall default in the performance of its obligations under this Lease or Landlord terminates this Lease by reason of a default of Tenant, Landlord at its option and without any obligation to do so, may require any transferee to attorn to Landlord.

ARTICLE 14: EVENTS OF DEFAULT AND REMEDIES

14.01.    Events of Default. Landlord and Tenant hereby agree that the occurrence of any one or more of the following events is a material default (sometimes referred to as an “Event of Default” by Tenant under this Lease:

14.01.1.    Tenant’s failure to make any payment of Base Rent, Additional Rent, Rent, Tenant’s share of Operating Expenses, Tenant’s share of Taxes, late charges, or any other payment required to be made by Tenant hereunder, as and when due, where such failure shall continue for a period of five (5) days after written notice thereof from Landlord to Tenant;

14.01.2.    Tenant’s failure to observe or perform any of the covenants, conditions or provisions of this Lease to be observed or performed by Tenant (other than those referenced in Section 14.01.1, above) where such failure shall continue for a period of thirty (30) days after written notice thereof from Landlord to Tenant, which thirty (30) day period shall be extendable up to ninety (90) days in the aggregate provided Tenant has commenced and is diligently pursuing cure of the same and provides notice thereof to Landlord;

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14.01.3.    Tenant’s permanent abandonment or vacating the Premises;

14.01.4.    Tenant’s (or any transferee of Tenant’s) attempt to make any Transfer of the Premises in violation of this Lease;

14.01.5.    (i) The making by Tenant or any guarantor of Tenant’s obligations hereunder of any general arrangement or general assignment for the benefit of creditors; (ii) Tenant or any guarantor becoming a “debtor” as defined in 11 U.S.C. 101 or any successor statute thereto (unless, in the case of a petition filed against Tenant or guarantor, the same is dismissed within sixty (60) days); (iii) the appointment of a trustee or receiver to take possession of substantially all of Tenant’s assets located at the Premises or of Tenant’s interest in this Lease, where possession is not restored to Tenant within thirty (30) days; (iv) the attachment, execution or other judicial seizure of substantially all of Tenant’s assets located at the Premises or of Tenant’s interest in this Lease, where such seizure is not discharged within thirty (30) days; or (v) the insolvency of Tenant In the event that any provision of this Section 14.04(e) is unenforceable under applicable law, such provision shall be of no force or effect;

14.01.6.    The discovery by Landlord that any financial statement, representation or warranty given to Landlord by Tenant, or by any guarantor of Tenant’s obligations hereunder, was materially false at the time given, Tenant acknowledging that Landlord has entered into this Lease in material reliance on such information;

14.01.7.    The failure of Tenant to comply with any of its obligations within the applicable specified timeframes under (i) Article 7 with respect to maintaining and evidencing the required insurance coverages; (ii) Article 15; (iii) Section 16.03; and (iv) Section 16.04, then, and in any such case, Landlord and its agents lawfully may, in addition to any remedies for any preceding breach, immediately or at any time thereafter without demand or notice and with or without process of law, enter upon any part of the Premises in the name of the whole or mail or deliver a notice of termination of the Term of this Lease addressed to Tenant at the Premises or any other address herein, and thereby terminate the Term and repossess the Premises as of Landlord’s former estate. At Landlord’s election, such notice of termination may be included in any notice of default. Upon such entry or mailing the Term shall terminate, all executory rights of Tenant and all obligations of Landlord will immediately cease, and Landlord may expel Tenant and all persons claiming under Tenant and remove their effects without any trespass and without prejudice to any remedies for arrears of Rent or prior breach; and Tenant waives all statutory and equitable rights to its leasehold (including rights in the nature of further cure or redemption, if any). If Landlord engages attorneys in connection with any failure to perform by Tenant hereunder, Tenant shall promptly reimburse Landlord for the fees of such attorneys on demand as Additional Rent. Without implying that other provisions do not survive, the provisions of this Article shall survive the Term or earlier termination of this Lease.

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Rent forgiveness, all allowances (including the Tenant Improvement Allowance and any portion of the Additional Improvement Allowance used) for (and/or Landlord expenses in designing and constructing) the Initial Tenant Improvements to ready the Premises for Tenant’s occupancy and the like, if any, have been agreed to by Landlord as inducements for Tenant faithfully to perform all of its obligations. For all purposes, upon the occurrence of any Event of Default and the lapse of the applicable cure period, if any, any such inducements shall be deemed void as of the date hereof as though such had never been included, and the aggregate amounts (or value) thereof will be deemed to be Additional Rent then immediately due. The foregoing will occur automatically without any further notice by Landlord, whether or not the Term is then or thereafter terminated and whether or not Tenant thereafter corrects such Event of Default.

14.02.    Remedies for Default.

14.02.1.    Reletting Expenses Damages. If the Term of this Lease is terminated for an Event of Default, Tenant covenants, as an additional cumulative obligation after such termination, to pay all of Landlord’s reasonable costs, including reasonable attorneys’ fees, related to Tenant’s Event of Default and in collecting amounts due and all reasonable expenses in connection with reletting, including tenant inducements to new tenants, brokerage commissions, fees for legal services, expenses of preparing the Premises for reletting and the like together with an administrative charge of ten percent (10%) of all the foregoing costs (“Reletting Expenses”). It is agreed that Landlord may (i) relet the Premises or part or parts thereof for a term or terms that may be equal to, less than or exceed the period that would otherwise have constituted the balance of the Term, and may grant such tenant inducements, including free rent, as Landlord in its sole discretion considers advisable, and (ii) make such alterations to the Premises as Landlord in its sole discretion considers advisable, and no failure to relet or to collect rent under any reletting shall operate to reduce Tenant’s liability. Any obligation to relet imposed by law will be subject to Landlord’s reasonable objectives of developing its property in a harmonious manner with appropriate mixes of tenants, uses, floor areas, terms and the like. Landlord’s Reletting Expenses together with all other sums provided for whether incurred prior to or after such termination will be due upon demand. Except in accordance with its remedy under Section 14.02.3, Landlord shall use commercially reasonable efforts to mitigate any damages resulting from a default by Tenant under this Lease existing beyond any requisite notice by Landlord and the expiration of any applicable grace period. Landlord’s obligation to mitigate damages after a default by Tenant under this Lease existing beyond any requisite notice by Landlord and the expiration of any applicable grace period shall be satisfied in full if Landlord undertakes to lease the Premises (or any portion thereof) to another tenant (a “Substitute Tenant”) in accordance with the following criteria: (a) Landlord shall have no obligation to solicit or entertain negotiations with any other prospective tenants for the Premises until Landlord obtains full and complete possession of the Premises including, without limitation, the final and unappealable legal right to relet the Premises free of any claim of Tenant; (b) Landlord shall not be obligated to lease or show the Premises, on a priority basis, or offer the Premises to a prospective tenant when other premises in the Building suitable for that prospective tenant’s use and other applicable requirements are (or will be on a timely basis) available; (c) Landlord shall not be obligated to lease the Premises to a Substitute Tenant for a rent less than the current fair market rent then prevailing for similar uses in comparable buildings in the same market area as the Building, nor shall Landlord be obligated to enter into a new lease under other terms and conditions that are unacceptable to Landlord, in Landlord’s good faith discretion; (d) Landlord shall not be obligated to enter into a lease with a Substitute Tenant whose use would: (i) violate any restriction, covenant, or requirement contained in the lease of another tenant of the Building; (ii) adversely affect, in Landlord’s reasonable opinion, the reputation of the Building; or (iii) be incompatible, in Landlord’s reasonable opinion, with the operation of the Building; and (e) Landlord shall not be obligated to enter into a lease with any proposed Substitute Tenant which does not have, in Landlord’s reasonable opinion, sufficient financial resources to operate the Premises in a first class manner and to fulfill all of the obligations in connection with the lease thereof as and when the same become due.

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14.02.2.    Termination Damages. If the Term of this Lease is terminated for default, unless and until Landlord elects lump sum liquidated damages described in the next paragraph, Tenant covenants, as an additional, cumulative obligation after any such termination, to pay punctually to Landlord all the sums and perform all of its obligations in the same manner as if the Term had not been terminated. In calculating such amounts Tenant will be credited with the net proceeds of any rent then actually received by Landlord from a reletting of the Premises after deducting all Rent that has not then been paid by Tenant, provided that Tenant shall never be entitled to receive any portion of the re-letting proceeds, even if the same exceed the Rent originally due hereunder.

14.02.3.    Lump Sum Liquidated Damages. If this Lease is terminated for default, Tenant covenants, as an additional, cumulative obligation after any such termination, to pay forthwith to Landlord at Landlord’s election made by written notice at any time after termination, as liquidated damages a single lump sum payment equal to the sum of (i) all sums to be paid by Tenant and not then paid at the time of such election, plus either, as Landlord elects, (ii) the excess of the present value of all of the Rent reserved for the residue of the Term (with Additional Rent deemed to increase ten percent (10%) in each year on a compounding basis) over the present value of the aggregate fair market rent and Additional Rent payable (if less than the Rent payable hereunder) on account of the Premises during such period, which fair market rent shall be reduced by reasonable projections of vacancies and by Landlord’s Reletting Expenses described above to the extent not theretofore paid to Landlord), or (iii) an amount equal to the sum of all of the Rent and other sums due under the Lease with respect to the twelve (12) month period next following the date of termination plus the amount of rent of any kind and the remaining unamortized cost of any Initial Tenant Improvements accrued and unpaid at the time of termination or repossession. (The Federal Reserve discount rate (or equivalent) shall be used in calculating such present values under clause (ii), and in the event the parties are unable to agree on such fair market rent, the matter shall be submitted, upon the demand of either party, to the office of the American Arbitration Association (or successor) closest to the Property, with a request for arbitration in accordance with the rules of the Association by a single arbitrator who shall be a licensed real estate broker with at least ten (10) years of experience in the leasing of 1,000,000 or more square feet of floor area of buildings similar in character and location to the Premises, whose decision shall be conclusive and binding on the parties.)

14.02.4.    Remedies Cumulative; Late Performance. The remedies to which Landlord may resort under this Lease, and all other rights and remedies of Landlord are cumulative, and any two or more may be exercised at the same time. Nothing in this Lease shall limit the right of Landlord to prove and obtain in proceedings for bankruptcy or insolvency an amount equal to the maximum allowed by any statute or rule of law in effect at the time; and Tenant agrees that the fair value for occupancy of all or any part of the Premises at all times shall never be less than the Base Rent and all Additional Rent payable from time to time. Tenant shall also indemnify and hold Landlord harmless in the manner provided elsewhere herein if Landlord shall become or be made a party to any claim or action (a) instituted by Tenant against any third party, or by any third party against Tenant, or by or against any person claiming Tenant; (b) for foreclosure of any lien for labor or material furnished to or for Tenant or such other person; (c) otherwise arising out of or resulting from any act or transaction of Tenant or such other person; or (d) necessary to protect Landlord’s interest under this Lease in a bankruptcy proceeding, or other proceeding under Title 11 of the United States Code, as amended.

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14.02.5.    Waivers; Accord and Satisfaction. No consent by Landlord or Tenant to any act or omission that otherwise would be a default shall be construed to permit other similar acts or omissions. Neither party’s failure to seek redress for violation or to insist upon the strict performance of any covenant, nor the receipt by Landlord of Rent with knowledge of any breach of covenant, shall be deemed a consent to or waiver of such breach. No breach of covenant shall be implied to have been waived unless such is in writing, signed by the party benefiting from such covenant and delivered to the other party; and no acceptance by Landlord of a lesser sum than the Rent due shall be deemed to be other than on account of the earliest installment of such Rent, Nor shall any endorsement or statement on any check or in any letter accompanying any check or payment be deemed an accord and satisfaction; and Landlord may accept such check or payment without prejudice to Landlord’s right to recover the balance of such installment or pursue any other right or remedy. The acceptance by Landlord of any Rent following the giving of any default and/or termination notice shall not be deemed a waiver of such notice. If Landlord commences any summary proceeding for possession of the Premises or in any action based on non-payment of Rent by Tenant hereunder, Tenant hereby waives the right to interpose any non-compulsory claim or counterclaim of whatever nature or description in any such proceeding.

14.02.6.    Landlord’s Curing. If Tenant fails to perform any covenant within any applicable cure period, then Landlord at its option may (without waiving any right or remedy for Tenant’s non-performance) at any time thereafter perform the covenant for the account of Tenant. Tenant shall upon demand reimburse Landlord’s cost (including reasonable attorneys’ fees) of so performing, together with an administrative charge equal to ten percent (10%) of such cost (“Administrative Charge”) on demand as Additional Rent Notwithstanding any other provision concerning cure periods, Landlord may cure any non-performance for the account of Tenant after such notice to Tenant, if any, as is reasonable under the circumstances if curing prior to the expiration of the applicable cure period is reasonably necessary to prevent likely damage to the Premises or possible injury to persons, or to protect Landlord’s interest in the Premises.

ARTICLE 15: LETTER OF CREDIT

Simultaneously with the execution and delivery of this Lease, Tenant shall deliver to Landlord a clean, irrevocable letter of credit in the Letter of Credit Amount (as defined in Article 1) in the form attached hereto as Exhibit J or otherwise satisfactory in form and content to Landlord and issued by an FDIC insured bank located in Boston reasonably satisfactory to Landlord in favor of Landlord. During the Term hereof, including any extensions thereof, or for any period that Tenant remains in possession of the premises following the expiration of the term, or for any period Tenant has obligations hereunder to Landlord that remain unsatisfied following the expiration of the term (as may be extended), and for ninety (90) days after the latest to occur of the foregoing (i.e., the expiration of the term (as may be extended), the date on which Tenant vacates and yields up the premises, etc.), the letter of credit shall be held to ensure the full and timely performance of Tenant9 s obligations under this Lease; which letter of credit may be drawn upon by Landlord and applied from time to time against outstanding obligations of Tenant hereunder without notice or demand. Tenant shall have no right to require Landlord to so draw and apply the letter of credit, nor shall Tenant be entitled to credit the same against rents or other sums payable hereunder. During the entire Term hereof, including any extension thereof, Tenant shall cause said letter of credit to be renewed, in identical form to that delivered herewith, no later than thirty (30) days prior to the date of expiration of same. Without limiting any other remedies of Landlord, in the event that Tenant fails to renew any letter of credit given hereunder at least thirty (30) days prior to the date of expiration thereof, then Landlord shall have the right to draw down the entire amount of said letter of credit and hold such sums as a cash deposit. If and to the extent that Landlord makes such use of the letter of credit, or any part thereof, the sum so applied by Landlord (from cash or from a drawing on the letter of credit) shall be restored to the letter of credit (or by a new letter of credit equal to the difference) by Tenant forthwith upon notice from Landlord, and failure to so restore (within the grace period applicable to Base Rent hereunder) shall be a default hereunder giving rise to all of Landlord’s rights and remedies applicable to a default in the payment of rent. In the event of an adverse change of circumstance relating to the bank issuing the letter of credit, or Landlord otherwise reasonably believes the financial conditions of the issuing bank has been substantially degraded, Landlord reserves the right to require Tenant to replace the letter of credit from time to time with a substitute similar letter of credit issued by another bank reasonably satisfactory to Landlord.

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Notwithstanding the foregoing, provided that: (a) Tenant has not been in default of any of its obligations under this Lease after the giving of any applicable notice or cure period within one (1) year prior to any Reduction Date, as hereinafter defined, in question, (b) Tenant is, as of such Reduction Date, not in default of its obligation under this Lease (provided, however, that if there is no reduction of the Letter of Credit Amount based upon Tenant’s failure to satisfy the condition set forth in this clause (b), then Tenant may subsequently achieve a reduction in the Letter of Credit Amount pursuant to this sentence at such time as Tenant cures such default, so long as the cure occurs within any applicable notice or cure period, this Lease is then in full force and effect, and Tenant is otherwise then in full compliance with its obligations under this Lease), and (c) this Lease is then both in full force and effect, the Letter of Credit Amount shall be reduced as of each “Reduction Date” as set forth below to the corresponding amount shown in the following schedule:

Reduction Date	New Reduced Letter of Credit Amount
First (1st) day of Lease Year 2	$117, 432.10
First (1st) day of Lease Year 3	$93, 945.68
First (1st) day of Lease Year 4	$70, 459.26

Any reduction in the Letter of Credit shall be accomplished by Tenant providing Landlord with a substitute Letter of Credit in the reduced amount in exchange for the existing Letter of Credit which Landlord is then holding, or by an amendment to the existing Letter of Credit then held by Landlord, in form and substance reasonably acceptable to Landlord, which is accepted by Landlord in writing. Landlord shall execute and deliver in connection therewith such acknowledgments and instruments as may be reasonably required to effectuate such reduction, including the delivery to Tenant or the issuer thereof of the Letter of Credit then held by Landlord.

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ARTICLE 16: PROTECTION OF LENDERS

16.01.    Subordination and Superiority of Lease. Tenant agrees that this Lease and the rights of Tenant hereunder will be subject and subordinate to any lien of the holder of any existing or future mortgage, and to the rights of any lessor under any ground or improvements lease of the Building (all mortgages and ground or improvements leases of any priority are collectively referred to in this Lease as “mortgage,” and the holder or lessor thereof from time to time as a “mortgagee”) and to all advances and interest thereunder and all modifications, renewals, extensions and consolidations thereof. With respect to future liens of any mortgage hereafter granted, Landlord will request that the mortgagee execute and deliver to Tenant an agreement (in such commercially reasonable form as such mortgagee may request) in which the mortgagee agrees that such mortgagee shall not disturb Tenant in its possession of the Premises upon Tenant’s execution thereof and attornment to such mortgagee as Landlord and performance of its Lease covenants (which conditions Tenant agrees with all mortgagees to perform). Upon such attornment, this Lease shall continue in full force and effect as a direct lease between the mortgagee and Tenant upon all of the terms, conditions and covenants as are set forth in this Lease, except that the mortgagee shall not be (i) liable in any way to Tenant for any act or omission, neglect or default on the part of Landlord under this Lease, (ii) responsible for any monies owing by or on deposit with Landlord to the credit of Tenant, (iii) subject to any counterclaim or setoff which theretofore accrued to Tenant against Landlord, (iv) bound by any amendment or modification of this Lease subsequent to such mortgage, or by any previous prepayment of Rent for more than one (1) month, which was not approved in writing by the mortgagee, (v) liable beyond mortgagee’s interest in the Property, (vi) responsible for the performance of any work to be done by the Landlord under this Lease to render the Premises ready for occupancy by the Tenant, or (vii) required to remove any person occupying the Premises or any part thereof, except if such person claims under the mortgagee. Tenant agrees that any present or future mortgagee may at its option unilaterally elect to subordinate, in whole or in part and by instrument in form and substance satisfactory to such mortgagee alone, the lien of its mortgagee (or the priority of its ground lease) to some or all provisions of this Lease. Notwithstanding anything to the contrary herein, Landlord shall exercise commercially reasonable efforts to obtain for Tenant, a duly-executed subordination, non-disturbance and attornment agreement from the existing mortgagee of the Building.

Tenant agrees that this Lease shall survive the merger of estates of ground (or improvements) lessor and lessee. Until a mortgagee (either superior or subordinate to this Lease) forecloses Landlord’s equity of redemption (or terminates or succeeds to a new lease in the case of a ground or improvements lease) no mortgagee shall be liable for failure to perform any of Landlord’s obligations (and such mortgagee shall thereafter be liable only after it succeeds to and holds Landlord’s interest and then only as limited herein). Tenant shall, if requested by Landlord or any mortgagee, give notice of any alleged non-performance on the part of Landlord to any such mortgagee provided that an address for such mortgagee has been designated to Tenant in writing, and Tenant agrees that such mortgagee shall have a separate, consecutive reasonable cure period of no less than thirty (30) days (to be reasonably extended in the same manner Landlord’s cure period is to be extended and for such additional periods as is necessary to allow such Mortgagee to take possession of the Property) following Landlord’s cure period during which such mortgagee may, but need not, cure any non-performance by Landlord. The agreements in this Lease with respect to the rights and powers of a mortgagee constitute a continuing offer to any person that may be accepted by taking a mortgage (or entering into a ground or improvements lease) of the Premises. This Section shall be self-operative, but in confirmation thereof, Tenant shall execute and deliver the subordination agreement in such form as any mortgagee may request.

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16.02.    Rent Assignment. If from time to time Landlord assigns this Lease or the rents payable hereunder to any person, whether such assignment is conditional in nature or otherwise, such assignment shall not be deemed an assumption by the assignee of any obligations of Landlord; but, subject to the limitations herein including Sections 16.01 and 10.02(b), the assignee shall be responsible only for non-performance of Landlord’s obligations that occur after it succeeds to, and only during the period it holds possession of, Landlord’s interest in the Premises after foreclosure or voluntary deed in lieu of foreclosure.

16.03.    Other Instruments. The provisions of this Article shall be self-operative; nevertheless, Tenant agrees to execute, acknowledge and deliver any subordination, non-disturbance attornment or priority agreements or other instruments conforming to the provisions of this Lease (and being otherwise commercially reasonable) from time to time requested by Landlord or any mortgagee, and further agrees that its failure to do so within fifteen (15) days after written request shall be a default for which this Lease may be terminated without further notice. Without limitation, where Tenant in this Lease indemnifies or otherwise covenants for the benefit of mortgagees, such agreements are for the benefit of mortgagees as third-party beneficiaries; and at the request of Landlord, Tenant from time to time will confirm such matters directly with such mortgagee.

16.04.    Estoppel Certificates. Within fifteen (15) days after Landlord’s request, Tenant shall execute, acknowledge and deliver to Landlord a written statement certifying: (i) that none of the terms or provisions of this Lease have been changed (or if they have been changed, stating how); (ii) that this Lease has not been canceled or terminated; (iii) the last date of payment of Base Rent and other charges and the time period covered; (iv) that Landlord is not in default under this Lease (or if Tenant states that Landlord is in default, describing it in reasonable detail); and (v) such other information with respect to Tenant or this Lease as Landlord may reasonably request or which any prospective purchaser or encumbrancer of the Property may require. Landlord may deliver any such statement by Tenant to any such prospective purchaser or encumbrancer, which may rely conclusively upon such statement as true and correct. If Tenant does not deliver such statement to Landlord within such fifteen (15) day period, Landlord, and any such prospective purchaser or encumbrancer, may conclusively presume and rely upon the following facts: (i) that the terms and provisions of this Lease have not been changed except as represented by Landlord; (ii) that this Lease has not been canceled or terminated except as otherwise represented by Landlord; (iii) that not more than one (1) month’s Base Rent or other charges have been paid in advance; and (iv) that Landlord is not in default under this Lease. In such event, Tenant shall be estopped from denying the truth of such facts.

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16.05.    Tenant’s Financial Condition. Tenant, within twenty (20) days after request from Landlord from time to time, shall deliver to Landlord Tenant’s annual audited financial statements for the latest available two (2) fiscal years, including the year ending no more than twelve (12) months prior to Landlord’s request, and quarterly financial statements certified in writing by Tenant’s chief financial officer; provided that absent the occurrence and continuance of an Event of Default Tenant shall not be required to provide any such financial statements more than twice in any twelve (12) month period. Landlord may deliver such financial statements to its investors, mortgagees, lenders and prospective mortgagees, lenders, investors and purchasers. Tenant represents and warrants to Landlord that each such financial statement shall be true and accurate as of its date. Except for publicly available information, Landlord shall use commercially reasonable efforts to maintain such financial statements on a confidential basis for the purposes set forth in this Section 16.05.

ARTICLE 17: MISCELLANEOUS PROVISIONS

17.01.    Landlord’s Consent Fees. In addition to fees and expenses in connection with Tenant Work, as described in Section 10.05, Tenant shall pay Landlord’s reasonable fees and expenses, including legal, engineering and other consultants’ fees and expenses, incurred in connection with Tenant’s request for Landlord’s consent under Article 13 (Assignment and Subletting) or in connection with any other act by Tenant that requires Landlord’s consent or approval under this Lease.

17.02.    Notice of Landlord’s Default. Landlord shall in no event be in default in the performance of any of Landlord’s obligations under this Lease unless and until Landlord shall have failed to perform such obligations within thirty (30) days, or such additional time as is reasonably required to correct any such default, after notice by Tenant to Landlord properly specifying wherein Landlord has failed to perform any such obligation. It is the express understanding and agreement of the parties and a condition of Landlord’s agreement to execute this Lease that, except as expressly provided in this Lease, in no event shall Tenant have the right to terminate this Lease or seek an abatement to or offset from Base Rent, Additional Rent or Rent as a result of Landlord’s default, but Tenant shall be entitled to seek all other remedies, at law or equity, as a result of such default, subject to the terms and conditions of this Lease. Tenant hereby waives its right to recover punitive, special or consequential damages arising out any act, omission Or default by Landlord (or any party for whom Landlord is responsible). This Lease and the obligations of Tenant hereunder shall not be affected or impaired because Landlord is unable to fulfill any of its obligations hereunder or is delayed in doing so, if such inability or delay is caused by reason of Force Majeure, and the time for Landlord’s performance shall be extended for the period of any such delay. Any claim, demand, right or defense by Tenant that arises out of this Lease or the negotiations which preceded this Lease shall be barred unless Tenant commences an action thereon, or interposes a defense by reason thereof, within six (6) months after the date of the inaction, omission, event or action that gave rise to such claim, demand, right or defense.

17.03.    Quiet Enjoyment. Landlord agrees that, so long as (i) Tenant is not in default under the terms of this Lease and (ii) this Lease is in full force and effect, Tenant shall lawfully and quietly hold, occupy and enjoy the Premises during the Term of this Lease without disturbance by Landlord or by any person claiming through or under Landlord, subject to the terms of this Lease and any encumbrances of record. The foregoing covenant of quiet enjoyment is in lieu of any other covenant, expressed or implied.

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17.04.    Interpretation. In any provision relating to the conduct, acts or omissions of Tenant, the term “Tenant” includes Tenant’s agents, employees, contractors, invitees, successors, assigns or others using the Premises with Tenant’s expressed or implied permission.

17.05.    Notices. All notices, requests and other communications required under this Lease shall be in writing, addressed as specified in Article 1, and shall be (i) personally delivered, (ii) sent by certified mail, return receipt requested, postage prepaid, (iii) delivered by a national overnight delivery service that maintains delivery records or (iv) sent by telecopier or facsimile machine (“fax”) that automatically generates a transmission report, with a copy also sent as described in clause (i), (ii) or (iii). All notices shall be effective upon delivery (or refusal to accept delivery); provided, however, that notice by fax or telecopy shall be effective when transmitted. Either party may change its notice address upon written notice to the other party.

17.06.    No Recordation. Tenant shall not record this Lease but, if required by applicable law in order to protect Tenant’s interest in the Premises, each party hereto agrees, on the request of the other, to execute a so-called memorandum of lease or short form lease in recordable form and complying with applicable law and reasonably satisfactory to Landlord’s attorneys. The party requesting or requiring such recording shall pay all expenses, transfer taxes and recording fees. In no event shall such document set forth the rent or other charges payable by Tenant under this Lease; and any such document shall expressly state that it is executed pursuant to the provisions contained in this Lease and is not intended to vary the terms and conditions of this Lease.

17.07.    Security Measures. Tenant acknowledges that Landlord shall have no obligation to provide guard service or other security measures for the benefit of the Premises or the Property, and Landlord shall have no liability to Tenant due to its failure to provide such services. Tenant assumes all responsibility for the protection of Tenant, its agents, employees, contractors and invitees and the property of Tenant and of Tenant’s agents, employees, contractors and invitees from acts of third parties. Nothing herein contained shall prevent Landlord, at Landlord’s sole option, from implementing security measures for the Building or any part thereof, in which event Tenant shall participate in such security measures and the cost thereof shall be included within the definition of Operating Expenses, and to the maximum extent permissible by law, Landlord shall have no liability to Tenant and its agents, employees, contractors and invitees arising out of Landlord’s provision of security measures. Landlord shall have the right, but not the obligation, to require all persons entering or leaving the Building to identify themselves to a security guard and to reasonably establish that such person should be permitted access to the Building.

17.08.    Corporate Authority. If Tenant is a business entity, then the person or persons executing this Lease on behalf of Tenant jointly and severally warrant and represent in their individual capacities that (a) Tenant is duly organized, validly existing and in good standing under the laws of the jurisdiction in which such entity was organized; (b) Tenant has the authority to own its property and to carry on its business as contemplated under this Lease; (c) Tenant is in compliance with all laws and orders of public authorities applicable to Tenant; (d) Tenant has duly executed and delivered this Lease; (e) the execution, delivery and performance by Tenant of this Lease (i) are within the powers of Tenant, (ii) have been duly authorized by all requisite action, (iii) will not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which Tenant is a party or by which it or any of its property is bound, and (iv) will not result in the imposition of any lien or charge on any of Tenant’s property, except by the provisions of this Lease; and (f) the Lease is a valid and binding obligation of Tenant in accordance with its terms. Tenant, if a business entity, agrees that breach of the foregoing warranty and representation shall at Landlord’s election be a default under this Lease for which there shall be no cure. Tenant shall from time to time, within ten (10) days after request by Landlord, deliver to Landlord any certification or other evidence requested from time to time by Landlord in its reasonable discretion, confirming Tenant’s compliance with these provisions. This warranty and representation shall survive the termination of the Term. Upon execution of this Lease, Tenant shall provide a board resolution or other entity vote authorizing the execution of this Lease on behalf of Tenant and identifying the person authorized to execute this Lease on behalf of Tenant together with a clerk’s or secretary’s certificate indicating that such authorized person has in fact executed this Lease. If Tenant shall fail to provide such resolution or vote, then the person executing this Lease on behalf of Tenant shall be deemed to have represented and warranted to Landlord that such person is duly authorized to execute and deliver this Lease on behalf of Tenant.

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17.09.    Intentionally Omitted.

17.10.    Joint and Several Liability; Right to Lease. If more than one (1) party signs this Lease as Tenant, they shall be jointly and severally liable for all obligations of Tenant. Landlord reserves the absolute right to effect such other tenancies in the Property as Landlord in its sole discretion shall determine, and Tenant is not relying on any representation that any specific tenant or number of tenants will occupy the Property.

17.11.    Force Majeure. If Landlord cannot perform any of its obligations under this Lease due to an event(s) of Force Majeure, the time provided for performing such obligations shall be extended by a period of time equal to the duration of the events. In case Tenant is prevented or delayed from performing any covenant or duty to be performed on Tenant’s part by reason of an event(s) of Force Majeure, Tenant shall not be deemed in default hereunder while such cause continues. The preceding sentence shall not apply to Tenant’s covenants and obligations to pay rent, additional charges and/or other charges or sums due Landlord hereunder or required to be paid to third parties hereunder. The preceding sentence shall not be interpreted to diminish Landlord’s rights hereunder to cure a breach of this Lease by Tenant or to recover the expense of such cure. As used in this Lease, an event or events of “Force Majeure” shall include strike or labor troubles, lockout, breakdown, accident, order, preemption or regulation of or by any governmental authority or failure to supply or inability by the exercise of reasonable diligence to obtain supplies, parts or employees necessary to furnish such services or because of war, civil commotion, or other emergency, or other extraordinary conditions of supply and demand, extraordinary weather conditions, so-called acts of God, or for any other cause beyond the party’s reasonable control.

17.12.    Limitation of Warranties. Landlord and Tenant expressly agree that there are and shall be no implied warranties of merchantability, habitability, suitability, fitness for a particular purpose or of any other kind arising out of this Lease, and there are no warranties that extend beyond those expressly set forth in this Lease.

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17.13.    No Other Brokers. Landlord and Tenant represent and warrant to each other that the Broker(s) named in Article 1 and Landlord’s Managing Agent are the only agents, Broker(s), finders or other parties with whom such party has dealt who may be entitled to any commission or fee with respect to this Lease or the Premises or the Property. Landlord and Tenant agree to indemnify and hold the other harmless from any claim, demand, cost or liability, including attorneys’ fees and expenses, asserted by any party other than the Broker(s) named in Article 1 and Landlord’s Managing Agent based upon dealings of that party with the indemnifying party. Landlord shall be responsible for the payment of any brokerage fees to the Broker(s) named in Article 1 and Landlord’s Managing Agent. The provisions of this Section shall survive the Term or early termination of this Lease.

17.14.    Applicable Law and Construction. This Lease may be executed in counterparts, shall be construed as a sealed instrument, and shall be governed exclusively by the provisions hereof and by the laws of the state where the Property is located without regard to principles of choice of law or conflicts of law. A facsimile signature to this Lease shall be sufficient to prove the execution by a party. The covenants of Landlord and Tenant are independent, and such covenants shall be construed as such in accordance with the laws of the state where the Property is located. If any provisions shall to any extent be invalid, the remainder shall not be affected. Other than contemporaneous instruments executed and delivered of even date, if any, this Lease contains all of the agreements between Landlord and Tenant relating in any way to the Premises and supersedes all prior agreements and dealings between them. There are no oral agreements between Landlord and Tenant relating to this Lease or the Premises. This Lease may be amended only by instrument in writing executed and delivered by both Landlord and Tenant. The provisions of this Lease shall bind Landlord and Tenant and their respective successors and assigns, and shall inure to the benefit of Landlord and its successors and assigns and of Tenant and its permitted successors and assigns, subject to Article 13. The titles are for convenience only and shall not be considered a part of the Lease. This Lease shall not be construed more strictly against one party than against the other merely by virtue of the fact that it may have been prepared primarily by counsel for one of the parties, it being recognized that both Landlord and Tenant have contributed substantially and materially to the preparation of this Lease. If Tenant is granted any extension or other option, to be effective the exercise (and notice thereof) shall be unconditional; and if Tenant purports to condition the exercise of any option or to vary its terms in any manner, then the option granted shall be void and the purported exercise shall be ineffective. The enumeration of specific examples of general provisions shall not be construed as a limitation of the general provision. Unless a party’s approval or consent is required by the express terms of this Lease not to be unreasonably withheld, such approval or consent may be withheld in the party’s sole discretion. The submission of a form of this Lease or any summary of its terms shall not constitute an offer by Landlord to Tenant; but a leasehold shall only be created and the parties bound when this Lease is executed and delivered by both Landlord and Tenant and approved by the holder of any mortgagee of the Premises having the right to approve this Lease. Nothing herein shall be construed as creating the relationship between Landlord and Tenant of principal and agent, or of partners or joint venturers or any relationship other than landlord and tenant. This Lease and all consents, notices, approvals and all other related documents may be reproduced by any party by any electronic means or by facsimile, photographic, microfilm, microfiche or other reproduction process and the originals may be destroyed; and each party agrees that any reproductions shall be as admissible in evidence in any judicial or administrative proceeding as the original itself (whether or not the original is in existence and whether or not reproduction was made in the regular course of business), and that any further reproduction of such reproduction shall likewise be admissible. If any payment in the nature of interest provided for in this Lease shall exceed the maximum interest permitted under controlling law, as established by final judgment of a court, then such interest shall instead be at the maximum permitted interest rate as established by such judgment. The term “Term” includes the Initial Term as it may be extended pursuant to Section 3.03.

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17.15.    Construction on the Property or Adjacent Property. Tenant acknowledges that Landlord is undertaking, or may undertake in the future, certain renovations in the Building or on or about the Property (the “Project”) including the right to make changes to the size, shape, location, number and extent of the improvements comprising the Property. In connection therewith, Landlord may, among other things, erect scaffolding or other necessary structures at the Property, limit or eliminate access to portions of the Property, including portions of the common areas, or perform work in or about the Building, which work may create noise, dust or leave debris in the Building. Landlord and its agents, employees, licensees and contractors shall also have the right to enter on the Property or Building to undertake work pursuant to any easement granted pursuant to the above paragraph; to shore up the foundations and/or walls of the Building; to erect scaffolding and protective barricades around, within or adjacent to the Building; and to do any other act necessary for the safety of the Building or the expeditious completion of such work. Tenant hereby agrees that such work and Landlord’s actions in connection therewith shall in no way constitute a constructive eviction of Tenant or entitle Tenant to any abatement of rent. Although Landlord shall use commercially reasonable efforts to minimize any material interference of Tenant’s use or occupancy of or access to the Premises, Landlord shall have no responsibility or for any reason be liable to Tenant for any direct or indirect injury to or interference with Tenant’s business arising from the foregoing work, nor shall Tenant be entitled to any compensation or damages from Landlord for any inconvenience or annoyance occasioned by such work or Landlord’s actions in connection therewith. Notwithstanding the foregoing, Tenant shall be entitled to a proportionate abatement of Base Rent in the event of a Tenant Use Interruption (as defined below), from the first (1st) business day following the Tenant Use Interruption Cure Period (as defined below) until the Tenant Use Interruption is cured. For the purposes hereof, a “Tenant Use Interruption” shall occur in the event (i) the Premises, or the applicable material portion thereof, shall be impacted by Landlord’s work on the Project, as set forth in this Section 17.15, to the extent that the Premises or the applicable material portion thereof is rendered untenantable for the entirety of the Tenant Use Interruption Cure Period (as defined below), (ii) such untenantability was not caused by Tenant, its employees, contractors, invitees or agents or by a casualty (in which event Section 12.01 shall control); (iii) Tenant in fact ceases to use the entire Premises, or the applicable material portion, for the entirety of the Tenant Use Interruption Cure Period; and (iv) such untenantability was the result of causes, events or circumstances within the Landlord’s reasonable control and the cure of such untenantability is within Landlord’s reasonable control. For the purposes hereof, the “Tenant Use Interruption Cure Period” shall be defined as five (5) consecutive business days after Landlord’s receipt of written notice from Tenant of the Tenant Use Interruption. Landlord shall have the right, in connection with the development, redevelopment, alteration, improvement, operation, maintenance, or repair of the Building, the Property or the Project, to subject the Property to easements for the construction, reconstruction, alteration, improvement, operation, repair or maintenance of elements thereof, for access and egress for parking, for the installation, maintenance, repair, replacement or relocation of utilities serving the Building, the Property or the Project and to subject the Property to such other rights, agreements, and covenants for such purposes as Landlord may determine. Tenant hereby agrees that this Lease shall be subject and subordinate to any such matters that do not unreasonably interrupt or interfere with Tenant’s use of the Premises. The foregoing sentence shall be self-operative, but Tenant hereby irrevocably appoints Landlord as Tenant’s attorney-in-fact to execute, acknowledge and deliver any documents appropriate to accomplish or confirm the same if Tenant fails to do so within ten (10) days after request therefor. Neither Tenant nor any persons acting under Tenant shall take any action to oppose the Project, nor shall the Tenant knowingly permit any persons acting under Tenant to take any action in opposition to the Project.

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17.16.    Vacancy at End of Term. If Tenant vacates substantially all of the Premises (or substantially all of a major portion of the Premises, including a floor of the Building) at any time within the last two (2) months of the Term, Landlord may enter the vacated Premises (or such portions) and commence demolition work or construction of leasehold improvements for future tenants, provided that such entry does not materially interfere with any continuing operations of Tenant in any other portions of the Premises. The exercise of such right by Landlord will not affect Tenant’s obligations to pay Base Rent or Additional Rent with respect to the Premises vacated (or such portions), which obligations shall continue without abatement until the end of the Term.

17.17.    Confidentiality. Tenant acknowledges and agrees that the terms of this Lease are confidential. Disclosure of the terms hereof could adversely affect the ability of Landlord to negotiate other leases with respect to the Building and may impair Landlord’s relationship with other tenants of the Building. Tenant agrees that it and its partners, officers, directors, employees, brokers, and attorneys, if any, shall not disclose the terms and conditions of this Lease to any other person or entity without the prior written consent of Landlord which may be given or withheld by Landlord, in Landlord’s sole discretion, except as required for financial disclosures or securities filings. It is understood and agreed that damages alone would be an inadequate remedy for the breach of this provision by Tenant, and Landlord shall also have the right to seek specific performance of this provision and to seek injunctive relief to prevent its breach or continued breach.

17.18.    OFAC CERTIFICATION AND INDEMNITY. Executive Order No. 13224 on Terrorist Financing, effective September 24, 2001 (the “Executive Order”), and the Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001 (Public Law 10756, the “Patriot Act”) prohibit certain property transfers. Tenant hereby represents and warrants to Landlord (which representations and warranties shall be deemed to be continuing and re-made at all times during the Term) that neither Tenant nor any stockholder, manager, beneficiary, partner, or principal of Tenant is subject to the Executive Order, that none of them is listed on the United States Department of the Treasury Office of Foreign Assets Control (“OFAC”) list of “Specially Designated Nationals and Blocked Persons”, as modified from time to time, and that none of them is otherwise subject to the provisions of the Executive Order or the Patriot Act. The most current list of “Specially Designated Nationals and Blocked Persons” can be found at http://www.treas.gov/offices/eotffc/ofac/sdn/index.html. Tenant shall from time to time, within ten days after request by Landlord, deliver to Landlord any certification or other evidence requested from time to time by Landlord in its reasonable discretion, confirming Tenant’s compliance with these provisions. No assignment or subletting shall be effective unless and until the assignee or subtenant thereunder delivers to Landlord written confirmation of such party’s compliance with the provisions of this subsection, in form and content satisfactory to Landlord. If for any reason the representations and warranties set forth in this subsection, or any certificate or other evidence of compliance delivered to Landlord hereunder, is untrue in any respect when made or delivered, or thereafter becomes untrue in any respect, then an event of default hereunder shall be deemed to occur immediately, and there shall be no opportunity to cure. Tenant shall indemnify, defend with counsel reasonably acceptable to Landlord, and hold Landlord harmless from and against, any and all liabilities, losses claims, damages, penalties, fines, and costs (including attorneys’ fees and costs) arising from or related to the breach of any of the foregoing representations, warranties, and duties of Tenant. The provisions of this subsection shall survive the expiration or earlier termination of this Lease for the longest period permitted by law.

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17.19.    WAIVER OF JURY TRIAL. LANDLORD AND TENANT HEREBY WAIVE THEIR RESPECTIVE RIGHT TO TRIAL BY JURY OF ANY CAUSE OF ACTION, CLAIM, COUNTERCLAIM OR CROSS-COMPLAINT IN ANY ACTION, PROCEEDING AND/OR HEARING BROUGHT BY EITHER LANDLORD AGAINST TENANT OR TENANT AGAINST LANDLORD ON ANY MATTER WHATSOEVER ARISING OUT OF, OR IN ANY WAY CONNECTED WITH, THIS LEASE, THE RELATIONSHIP OF LANDLORD AND TENANT, TENANTS USE OR OCCUPANCY OF THE PREMISES, OR ANY CLAIM OF INJURY OR DAMAGE, OR THE ENFORCEMENT OF ANY REMEDY UNDER ANY LAW, STATUTE, OR REGULATION, EMERGENCY OR OTHERWISE, NOW OR HEREAFTER IN EFFECT.

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Executed to take effect as a sealed instrument on the Date of the Lease first set forth above.

LANDLORD:

128 SPRING STREET LEXINGTON, LLC

By: /s/ Stephen Faber

Name: Stephen Faber

Title: Authorized Signatory

TENANT:

CYTEIR THERAPEUTICS, INC.

By: /s/ Markus Renschler

Name: Markus Renschler, MD

Title: President & CEO

  Duly Authorized

Exhibit A

Plan of Leased Premises

A-1

Exhibit B

Rules and Regulations

1. If Tenant requires telephone, data, burglar alarm or similar service, the cost of purchasing, installing and maintaining such service shall be borne solely by Tenant No boring or cutting for wires will be allowed without the prior written consent of Landlord. Landlord shall direct electricians as to where and how telephone, data, and electrical wires are to be introduced or installed. The location of burglar alarms, telephones, call boxes or other office equipment affixed to the Premises shall be subject to the prior written approval of Landlord.

2. Tenant shall not place a load upon any floor of its Premises, including mezzanine area, if any, which exceeds the load per square foot that such floor was designed to carry and that is allowed by law. Heavy objects shall stand on such platforms as determined by Landlord to be necessary to properly distribute the weight Landlord will not be responsible for loss of or damage to any such equipment or other property from any cause, and all damage done to the Building by maintaining or moving such equipment or other property shall be repaired at the expense of Tenant.

3. Tenant shall not install any radio or television antenna, satellite dish, loudspeaker or other device on the roof or exterior walls of the Building without Landlord’s prior written consent which consent shall be in Landlord’s sole discretion.

4. Tenant shall not mark, drive nails, screw or drill into the partitions, woodwork, plaster or drywall (except for pictures and general office uses) or in any way deface the Premises or any part thereof. Tenant shall not affix any floor covering to the floor of the Premises or paint or seal any floors in any manner except as approved by Landlord. Tenant shall repair any damage resulting from noncompliance with this rule.

5. No cooking shall be done or permitted on the Premises, except that Underwriters’ Laboratory approved microwave ovens or equipment for brewing coffee, tea, hot chocolate and similar beverages shall be permitted, provided that such equipment and use is in accordance with all applicable federal, state and city laws, codes, ordinances, rules and regulations.

6. All trash and refuse shall be contained in suitable receptacles at locations approved by Landlord. Tenant shall not place in the trash receptacles any personal trash or material that cannot be disposed of in the ordinary and customary manner of removing such trash without violation of any law or ordinance governing such disposal.

7. Tenant shall comply with all safety, fire protection and evacuation procedures and regulations established by Landlord or any governing authority.

8. Tenant assumes all responsibility for securing and protecting its Premises and its contents including keeping doors locked and other means of entry to the Premises closed.

B-1

9. Tenant shall not use any method of heating or air conditioning other than that supplied by Landlord without Landlord’s prior written consent.

10. No person shall go on the roof without Landlord’s permission.

11. Canvassing, soliciting, distribution of handbills or any other written material in the Building or Project Area is prohibited and each tenant shall cooperate to prevent the same. No tenant shall solicit business from other tenants or permit the sale of any goods or merchandise in the Building or Project Area without the written consent of Landlord.

12. Any equipment belonging to Tenant which causes noise or vibration that may be transmitted to the structure of the Building or to any space therein to such a degree as to be objectionable to Landlord or to any tenants in the Building shall be placed and maintained by Tenant, at Tenant’s expense, on vibration eliminators or other devices sufficient to eliminate the noise or vibration.

13. Driveways, sidewalks, halls, passages, exits, entrances and stairways (“Access Areas”) shall not be obstructed by tenants or used by tenants for any purpose other than for ingress to and egress from their respective premises. Access areas are not for the use of the general public and Landlord shall in all cases retain the right to control and prevent access thereto by all persons whose presence, in the judgment of Landlord, shall be prejudicial to the safety, character, reputation and interests of the Building or its tenants.

14. Landlord reserves the right to designate the use of parking areas and spaces. Tenant shall not park in visitor, reserved, or unauthorized parking areas. Tenant and Tenant’s guests shall park between designated parking lines only and shall not park motor vehicles in those areas designated by Landlord for loading and unloading. Vehicles in violation of the above shall be subject to being towed at the vehicle Owner’s expense. Vehicles parked overnight without prior written consent of the Landlord shall be deemed abandoned and shall be subject to being towed at vehicle owner’s expense. Tenant will from time to time, upon the request of Landlord, supply Landlord with a list of license plate numbers of vehicles owned or operated by its employees or agents.

15. No trucks, tractors or similar vehicles can be parked anywhere other than in Tenant’s own truck dock area. Tractor-trailers which must be unhooked or parked with dolly wheels beyond the concrete loading areas must use steel plates or wood blocks under the dolly wheels to prevent damage to the paving surfaces. No parking or storing of such trailers will be permitted in the parking areas or on streets adjacent thereto.

16. No sign, placard, picture, advertisement, name or notice (collectively referred to as “Signs”) shall be installed or displayed on any part of the outside of the Building without the prior written consent of the Landlord which consent shall be in Landlord’s sole discretion. All approved Signs shall be printed, painted, affixed or inscribed at Tenant’s expense by a person or vendor approved by Landlord and shall be removed by Tenant at Tenant’s expense upon vacating the Premises. Landlord shall have the right to remove any Sign installed or displayed in violation of this rule at Tenant’s expense and without notice. Subject to approval by Landlord and by the Town of Lexington, Tenant will have the right to signage similar to that of other tenants of the Building. All such signage will be installed, maintained, and, at the end of the Term, removed by Tenant at its sole expense, with Tenant repairing any damage caused by same.

B-2

17. During periods of loading and unloading, Tenant shall not unreasonably interfere with traffic flow and loading and unloading areas of other tenants. All products, materials or goods must be stored within the Tenant’s Premises and not in any exterior areas, including, but not limited to, exterior dock platforms, against the exterior of the Building, parking areas and driveway areas. Tenant agrees to keep the exterior of the Premises clean and free of nails, wood, pallets, packing materials, barrels and any other debris produced from their operation.

18. Tenant shall not permit any motor vehicles to be washed or mechanical work or maintenance of motor vehicles to be performed on any portion of the Premises or parking lot.

19. Tenant shall not permit smoking or carrying of lighted cigarettes or cigars in areas reasonably designated by Landlord or any applicable governmental agencies as non-smoking areas.

20. Canvassing, soliciting, distribution of handbills or any other written material in the Building or Project Area is prohibited and each tenant shall cooperate to prevent the same. No tenant shall solicit business from other tenants or permit the sale of any goods or merchandise in the Building or Project Area without the written consent of Landlord.

21. Tenant shall not permit any animals, other than seeing-eye dogs, to be brought or kept in or about the Premises or any common area of the property.

22. Tenant shall not alter any lock or other access device or install a new or additional lock or access device or bolt on any door of its Premises without the prior written consent of Landlord. Tenant, upon the termination of its tenancy, shall deliver to Landlord the keys or other means of access to all doors.

23. These Rules and Regulations are in addition to, and shall not be construed to in any way modify or amend, in whole or in part, the terms, covenants, agreements and conditions of any lease of any premises in the Building. Landlord may waive any one or more of these Rules and Regulations for the benefit of any tenant or tenants, and any such waiver by Landlord shall not be construed as a waiver of such Rules and Regulations for any or all tenants.

24. Landlord reserves the right to make such other and reasonable rules and regulations as in its judgment may from time to time be needed for safety and security, for care and cleanliness of the Building and for the preservation of good order in and about the Building. Tenant agrees to abide by all such rules and regulations herein stated and any additional rules and regulations which are adopted provided that the same do not conflict with the terms and conditions of this Lease or Tenant’s rights hereunder. Tenant shall be responsible for the observance of all of the foregoing rules by Tenant’s employees, agents, clients, customers, invitees and guests.

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Exhibit C

Rules and Regulations for Design and Construction of Tenant Work

1. DEFINITIONS

1.1.	Building:	Ledgemont Technology Center, 99 Hayden Avenue, Lexington, MA
1.2.	Property Manager:	Related Beal LLC. or such other individual/entity as landlord may designate, from time to time.
1.3.	Consultant:	Any architectural, engineering or design consultant engaged by a Tenant in connection with Tenant Work.
1.4.	Contractor:	Any Contractor engaged by Tenant of the Building for the performance of any Tenant Work, and any Subcontractor employed by any such Contractor,
1.5.	Plans:	All architectural, electrical and mechanical construction drawings and specifications required for the proper construction of the Tenant Work.
1.6.	Regular Business Hours:	Monday through Friday, 8:00 a.m. through 6:00 p.m., holidays and weekends excluded.
1.7.	Tenant:	Any occupant of the Building.
1.8.	Tenant Work:	Any alterations, improvements, additions, repairs or installations on the building performed by or on behalf of any Tenant.
1.9.	Tradeperson:	Any employee (including, without limitation, any mechanic laborer, or Tradeperson) employed by a Contractor performing Tenant Work.

2. GENERAL

2.1. All Tenant Work shall be performed in accordance with these Rules and Regulations and the applicable provisions of the Lease and to current local and state code.

2.2. The provisions of these Rules and Regulations shall be incorporated in all agreements governing the performance of all Tenant Work, including, without limitation, any agreements governing services to be rendered by each Contractor and Consultant.

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2.3. Except as otherwise provided in these Rules and Regulations, all inquiries, submissions and approvals in connection with any Tenant Work shall be processed through the Property Manager.

3. INTENTIONALLY OMITTED.

4. RECONSTRUCTION NOTIFICATION AND APPROVALS

4.1. Approval to Commence Work:

A) Tenant shall submit to Property Manager, for the approval of the Landlord, the names of all prospective Contractors and Certificates of Insurance, prior to issuing any bid packages to such Contractors.

B) No Tenant Work shall be undertaken by any Contractor or Tradeperson unless and until all the matters set forth in Section 4.2 below have been received for the Tenant Work in question and unless the Property Manager has approved the matters set forth in Section 4.2 below.

4.2. No Tenant Work shall be performed unless, at least two (2) weeks before any Tenant Work is to begin, all of the following have been provided to the Property Manager and approved. In the event that Tenant proposes to change any of the following, the Property Manager shall be immediately notified of such change and such change shall be subject to the approval of the Property Manager:

A) Schedule for the work, indication start and completion dates, any phasing and special working hours, and also a list of anticipated shutdowns of building systems.

B) List of all Contractors and Subcontractors, including addresses, telephone numbers, emergency (after hours) telephone numbers, trades employed, and the union affiliation, if any, of each Contractor and Subcontractor.

C) Names and telephone numbers of the supervisors of the work.

D) Copies of all necessary governmental permits, licenses and approvals.

E) Proof of current insurance, to the limits set out in Exhibit D to the Lease and Regulations, naming Landlord (128 Spring Street Lexington, LLC) and Landlord’s designees as additional insured parties.

F) Notice of the involvement of any Contractor in any ongoing threatened labor dispute.

G) Payment, Performance and Lien Bonds from sureties acceptable to Landlord, in form acceptable to Landlord, naming Landlord as an additional oblige.

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H) Evidence that Tenant has made provision for either written waivers of lien from all Contractors and suppliers of material, or other appropriate protective measures approved by Landlord.

I) A pre-existing condition survey as specified in Section 7.2(C).

4.3. Reporting Incidents: All accidents, disturbances, labor disputes or threats thereof, and other noteworthy events pertaining to the Building or the Tenant’s property shall be reported immediately to the Property Manager. A written report must follow within twenty-four (24) hours.

5. CONSTRUCTION SCHEDULE

5.1. Coordination:

A) All Tenant Work shall be carried out expeditiously and with minimum disturbance and disruption to the operation of the Building and without causing discomfort, inconvenience, or annoyance to any of the other tenants or occupants of the Building or the public at large.

B) All schedules for the performance of construction, including materials deliveries, must be coordinated through the Property Manager. The Property Manager shall have the right, without incurring any liability to any Tenant, to stop activities and/or to require rescheduling of Tenant Work based upon adverse impact on the tenants or occupants of the Building or on the maintenance or operation of the Building.

C) If any Tenant Work requires the shutdown of risers and mains for electrical, mechanical, sprinkler, and plumbing work, such work shall be supervised by a representative of Landlord, the cost of which shall be charged directly to the tenant at the prevailing building rate. No Tenant Work will be performed in the Building’s mechanical or electrical equipment rooms without both Landlord’s prior approval and the supervision of a representative of Landlord, the cost of which shall be reimbursed by the Tenant to the Landlord. Tenant shall provide the Property Manager with at least one week to schedule such work.

5.2. Time Restrictions:

A) Subject to Section 5.1 of these Rules and Regulations, general construction work will generally be permitted at all times, unless such work affects other tenants or occupants of the building or poses a safety concern at which time it will need be scheduled during non-business hours.

B) Tenant shall provide the Property Manager with at least forty-eight (48) hours’ notice before proceeding with Special Work, as hereinafter defined, and such Special Work will be permitted only at times agreed to by the Property Manager during periods outside of Regular Business Hours. “Special Work” shall be defined as the following operations:

1. All utility disruptions, shutoffs and turnovers.

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2. Activities involving high levels of noise, including demolition, coring, drilling and ramsetting.

3. Activities resulting in excessive dust or odors, including demolition, staining and spray painting.

4. All construction work which will require access to multi-tenant areas or other tenant areas.

C) The delivery of construction materials to the Building, their distribution within the Building, and the removal of waste materials shall also be confined to periods outside Regular Business Hours, unless otherwise specifically permitted in writing by the Property Manager. Costs for use of the freight elevator after Regular Business Hours shall be billed directly to such tenant at the then prevailing rate.

D) If coordination, labor disputes or other circumstances require, the Property Manager may change the hours during which regular construction work can be scheduled and/or restrict or refuse entry to and exit from the Building by any Contractor.

6. CONTRACTOR PERSONNEL

6.1. Work in History:

A) All Contractors shall be responsible for employing skilled and competent personnel and suppliers who shall abide by the rules and regulations herein set forth as amended from time to time by Landlord.

B) No Tenant shall at any time, either directly or indirectly, employ, permit the employment, or continue the employment of any contractor if such employment or continued employment will or does interfere or cause any labor disharmony, coordination difficulty, delay or conflict with any other contractors engaged in construction work in or about the Building or the complex in which the Building is located.

C) Should a work stoppage or other action occur anywhere in or about the Building as a result of the presence, anywhere in the Building, or a Contractor engaged directly or indirectly by a Tenant, or should such Contractor be deemed by Landlord to have violated any applicable rules or regulations, then upon twelve hours written notice, Landlord may, without incurring any liability to Tenant or said contractor, require any such Contractor to vacate the premises demised by such Tenant and the Building, and to cease all further construction work therein.

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6.2. Conduct:

A) While in or about the Building, all Tradepersons shall perform in a dignified, quiet, courteous, and professional manner at all times. Tradepersons shall wear clothing suitable for their work and shall remain full attired at all times. All Contractors will be responsible for their Tradepersons. proper behavior and conduct.

B) The Property Manager reserves the right to remove any one who, or any contractor which; is causing a disturbance to any tenant or occupant of the Building or any other person using or servicing the Building; is interfering with the work of others; or is in any other way displaying conduct or performance not compatible with the Landlord’s standards.    

6.3. Access:

A) All Contractors and Tradepersons shall contact the Property Manager prior to commencing work, to confirm work location and Building access, including elevator usage and times of operation. Access to the Building before and after Regular Business Hours or any other hours designated from time to time by the Property Manager and all day on weekends and holidays will only be provided when forty- eight (48) hours advanced notice is given to the Property Manager.

B) No Contractor or Tradepersons will be permitted to enter any private or public space in the Building, other than the common areas of the Building necessary to give direct access to the premises of Tenant for which he has been employed, without the prior approval of the Property Manager.

C) All Contractors and Tradepersons must obtain permission from the Property Manager prior to undertaking work in any space outside of the Tenant’s premises. This requirement specifically includes ceiling spaces below the premises where any work required must be undertaken at the convenience of the affected Tenant and outside of Regular Business Hours. Contractors undertaking such work shall ensure that all work, including work required to reinstate removed items and cleaning, be completed prior to opening of the next business day. Any cleaning or repairs costs incurred by Landlord, as a result of work outside the construction area shall be charged to the Tenant.

D) Contractors shall ensure that all furniture, equipment and accessories in areas potentially affected by any Tenant Work shall be adequately protected by means of drop cloths or other appropriate measures. In addition, all Contractors shall be responsible for maintaining security to the extent required by the Property Manager.

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E) Temporary access doors for tenant construction areas connecting with a public corridor will be building standards, i.e., door, frame, hardware and lockset. A copy of the key will be furnished to the Property Manager.

6.4. Safety:

A) All Contractors shall police ongoing construction operations and activities at all times, keeping the premises orderly, maintaining cleanliness in and about the premises, and ensuring safety and protection of all areas, including truck docks, elevators, lobbies, and all other public areas which are used for access to the premises.

B) All Contractors shall appoint a supervisor who shall be responsible for all safety measures, as well as for compliance with all applicable government laws, ordinances, rules and regulations such as, for example, “OSHA” and “Right-to-Know” legislation.

C) Any damage caused by Tradepersons or other Contractor employees shall be the responsibility of the Tenant employing the Contractor. Costs for repairing such damage shall be charged directly to such Tenant.

6.5. Parking:

A) No parking of contractor or sub-contractor vehicles will be provided in the truck dock, handicapped or fire access lanes, or any private ways in or surrounding the property. Vehicles so parked will be towed at the expense of the Tenant who has engaged the Contractor for whom the owner of such vehicle is employed.

B) Garage parking is available on-site.

7. BUILDING MATERIALS

7.1. Delivery:

A) All deliveries of construction materials shall be made at the predetermined times approved by the Property Manager and shall be effected safely and expeditiously only at the location determined by the Property Manager.

7.2. Transportation in Building:

A) Distribution of materials from delivery point to the work area in the Building shall be accomplished with the least disruption to the operation of the Building possible. Elevators will be assigned for material delivery and will be controlled by the Building Management.

B) Contractors shall provide adequate protection to all carpets, wall surfaces, doors and trim in all public areas through which materials are transported. Contractors shall continuously clean all such areas. Protective measures shall include runners over carpet, padding in elevators and any other measures determined by the Property Manager.

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C) Any damage caused to the Building through the movement of construction materials or otherwise shall be the responsibility of Tenant who has engaged the Contractor involved. Charges for such damage will be submitted by the Landlord directly to the Tenant. Prior to the commencement of tenant work, a pre-existing condition survey shall be submitted to the Property Manager. Such survey shall be used at the completion of the project to determine, if any, the extent of damage to the building systems or finishes.

7.3. Storage and Placement:

A) All construction materials shall be stored only in the premises where they are to be installed. No storage of materials will be permitted in any public areas, loading docks or corridors leading to the premises.

B) No flammable, toxic, or otherwise hazardous materials may be brought in or about the Building unless all of the following are met: (i) authorized by the Property Manager, (ii) all applicable laws, ordinances, rules and regulations are complied with, and (iii) all necessary permits have been obtained. All necessary precautions shall be taken by the contractor handling such materials against damage or injury caused by such materials.

C) All materials required for the construction of the premises must comply with Building Standards, must conform with the plans and specifications approved by Landlord, and must be installed in the locations shown on the drawings approved by the Landlord.

D) All work shall be subject to supervision and inspection by Landlord’s Representative.

E) No alterations to approved plans will be made without prior knowledge and approval of the Property Manager. Such changes shall be documented on the as-build drawings required to be delivered to Landlord pursuant to Paragraph 10 of the rules and regulations.

F) All protective devices (e.g., temporary enclosures and partitions) and materials, as well as their placement, must be approved by the Property Manager.

G) It is the responsibility of Contractors to ensure that the temporary placement of materials does not impose a hazard to the Building or its occupants, either through overloading, or interference with Building systems, access, egress or in any other manner whatsoever.

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H) All existing and/or new openings made through the floor slab for piping, cabling, etc. must be sealed per code. All holes in the floor slab at abandoned floor outlets, etc. need to be filled with solid concrete.

7.4. Salvage and Waste Removal:

A) All rubbish, waste and debris shall be neatly and cleanly removed from the Building by Contractors daily unless otherwise approved by the Property Manager. The Building’s trash compactor shall not be used for construction or other debris. For any demolition and debris, each Contractor must make arrangements with the Property Manager for the scheduling and location of an additional dumpster to be supplied at the cost of the Tenant engaging such Contractor. Where, in the opinion of the Property Manager, such arrangements are not practical, such Contractors will make alternative arrangements for removal at the cost of the Tenant engaging such Contractors.

B) Toxic or flammable materials are to be properly removed daily and disposed of in full accordance with all applicable laws, ordinances, rules and regulations.

C) Contractors shall, prior to removing any item (including, without limitation, building standard doors, frames and hardware, light fixtures, ceiling diffusers, ceiling exhaust fans, sprinkler heads, fire horns, ceiling speakers and smoke detectors) from the Building, notify the Property Manager that it intends to remove such item. At the election of Property Manager, Contractors shall deliver any such items to the Property Manager, Such items will be delivered, without cost, to an area designated by the Property Manager which area shall be within the Building or the complex in which the Building is located.

8. PAYMENT OF CONTRACTORS

Tenant shall promptly pay the cost of all Tenant Work so that Tenant’s premises and the Building shall be free of liens for labor or materials. If any mechanic’s lien is filed against the Building or any part thereof which is claimed to be attributable to the Tenant, its agents, employees or contractors, Tenant shall give immediate notice of such lien to the Landlord and shall promptly discharge the same by payment or filing any necessary bond within 10 days after Tenant has first notice of such mechanic’s lien.

9. CONFLICT BETWEEN RULES AND REGULATIONS AND LEASE

In the event of any conflict between the Lease and these Rules and Regulations, the terms of the Lease shall control.

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10. GENERAL

10.1. These Rules and Regulations are in addition to, and shall not be construed to in any way modify or amend, in whole or in part, the terms, covenants, agreements and conditions of any lease of any premises in the Building. Landlord may waive any one or more of these Rules and Regulations for the benefit of any tenant or tenants, and any such waiver by Landlord shall not be construed as a waiver of such Rules and Regulations for any or all tenants.

10.2. Landlord reserves the right to make such other and reasonable rules and regulations as in its judgment may from time to time be needed for safety and security, for care and cleanliness of the Building and for the preservation of good order in and about the Building. Tenant agrees to abide by all such rules and regulations herein stated and any additional rules and regulations which are adopted. Tenant shall be responsible for the observance of all of the foregoing rules by Tenant’s employees, agents, clients, customers, invitees and guests.

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SCHEDULE A OF EXHIBIT C

RULES AND REGULATIONS

FOR DESIGN AND CONSTRUCTION OF TENANT WORK

Ledgemont Center

BASE BUILDING CHARGES

Contractors desiring to work on the Building Systems must coordinate all work with the Management Office at 781-861-7786.

All work must be scheduled a minimum of one week prior to the start of work. A work order will be issued listing the system affected and the time of shutdown. No work will commence until the work order has been signed by an authorized representative of the construction company.

Contractors must obtain credit approval from the Management Office prior to any work authorization.

	Fire Alarm Shutdown		Reconnect		Shutdown
8:00 a.m. to 5:00 p.m.	$	125.00		N/C
5:00 p.m. to 8:00 a.m.	$	175.00	$	175.00
Saturday	$	225.00	$	225.00
Sunday	$	250.00	$	250,00

Labor charge (per person) for Fire Alarm Watch or Sprinkler System Shutdown (required when servicing or testing any life safety device):

8:00 a.m. to 5:00 p.m.	$40.00 per hour
5:00 p.m. to 8:00 a.m.	$60.00 per hour
Saturday	$60.00 per hour
Sunday	$80.00 per hour

Contractor may not proceed with any work until authorization to begin work has been obtained from the Management Office. A separate request is to be issued for each day in which the Life Safety work is being performed.

Contractor will be fined $1, 500.00 for each and every false alarm caused by contractors’ employees or their actions. Contractor will be fined $500.00 for every smoke detector covered by the contractor or their subcontractors.

$30.00 Per Hr (3 Hr Min) Contractors must pay a minimum of $1, 500.00 to repair the elevator cabs if damaged.

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SCHEDULE B OF EXHIBIT C

RULES AND REGULATIONS

FOR DESIGN AND CONSTRUCTION OF TENANT WORK

INSTALLATION OF CABLES

1.1 Computer and Telephone Cables

1.1.1 Layout

A layout of cables must be submitted to the Property Manager for approval prior to installation.

1.1.2 Installation

A) Cables installed above the ceiling must be Teflon coated or encased in metal conduit.

B) Cables must be tagged every 15’ and color coded.

C) Cables must be properly affixed to the framing above the duct work so that they are self-supporting. Do not fasten to light fixtures.

D) Cables must not sag and will be installed in the shortest possible runs.

E) Connections (connectors, splices, etc.) must be securely installed so that they will not pull apart if cable is accidentally touched or pulled.

1.2 Electrical Floor Outlet Cables

1.2.1 Layout

A layout of cables must be submitted to the Property Manager for approval prior to installation.

1.2.2 Installation

A) Cables must be tagged every 15’ and color coded.

B) Runs will be as short and as free of slack as possible secured per code requirements.

C) Cables are to be installed in tenant’s own ceiling then down partitions into the ceiling of the tenant below.

D) Cables must be properly secured so that they are self-supporting.

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E) All connections (connectors, splices, etc.) must be located in the tenant’s own space to avoid damage from below.

F) Cables must be secured with clamps where they pass through the floor to prevent connections from separating.

G) Where feasible, install cables above duct work and other materials in the ceiling.

1.3 Electrical Work

1.3.1 All power wiring in Mechanical Rooms, Electric Rooms and Telephone rooms must be in EMT.

1.4 Security System

1.4.1 Layout

A layout of the security system wiring must be submitted to the Property Manager for approval prior to installation.

1.4.2 Installation

A) All wiring for the security system will be tagged every 15’.

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SCHEDULE C OF EXHIBIT C

RULES AND REGULATIONS

FOR DESIGN AND CONSTRUCTION OF TENANT WORK

1. WELDING AND HEAT CUTTING WORK

1.1 Definition

Welding and heat cutting activities as well as soldering and brazing shall be included in “Special Work”, category as defines in Section 5.2(B). They require the tenant to provide the Property Manager with at least forty-eight (48) hours’ notice before proceeding and must be performed during periods outside of regular business hours.

1.2 Permitting

The Contractor must obtain a permit from the Lexington Fire Department before commencing work.

1.3 Precautions

Because welding and other hot work is a fire hazard, the Contractor must observe the following precautions and procedures (when possible, work should be done in a non-combustible area):

A) No sprinkler impairments are allowed during “Special Work” and while the fire watch is in place. The sprinkler impairment restriction is for the floor the “Special Work” is taking place on and the floor above and the floor below.

B) Smoke Detectors in the work area should be de-activated by the Building Manager for the duration of the work. The Property Manager will re-activate smoke detectors when the work is complete.

C) Combustible materials shall be located at least fifty (50) feet from hot work operations and shall be covered with non-combustible materials.

D) All flammable liquids and other hazards must be removed.

E) All floor and wall openings must be covered with non-combustible material.

F) Containers, tanks, ducts, etc. must be cleaned and purged of flammable vapors, liquids, dusts etc.

G) A minimum of one multipurpose ABC rated portable fire extinguisher must be provided within ten (10) feet of the work area. The extinguisher should be fully charged and have been properly serviced within the last year. It is the responsibility of the contractor to provide fire extinguishers. Building extinguishers should not be used. A standpipe hose should also be readily available.

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H) A fire watch should be maintained on the floor levels where the work was conducted plus the next two floors below for at least one hour after welding or burning has ceased. The fire watch shall consist of a member of the Lexington Fire Department If there is a chance that slag could enter into a utility or elevator shaft, then the fire watch should cover the base of the shaft as well as the intermediate floors,

I) If determined, a member of the Lexington Fire Department shall be on site, at Tenant cost, for any “Special Work”.

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Exhibit D

Tenant Work Insurance Schedule

Tenant shall, at its own expense, maintain and keep in force, or cause to be maintained and kept in force by any general contractors, sub-contractors or other third party entities where required by contract, throughout any period of alterations to the Premises or the Building by Tenant, the following insurance coverages:

(1)     Property Insurance, “All-Risk” or “Special” Form property insurance, and/or Builders Risk coverage for major renovation projects, including, without limitation, coverage for fire? and earthquake; boiler and machinery (if applicable); sprinkler damage; vandalism; malicious mischief coverage on all equipment, furniture, fixtures, fittings, tenants work, improvements and betterments installed on or about the Premises by or on behalf of Tenant, business income, extra expense, merchandise, inventory/stock, contents, and personal property of Tenant or any party taking by or through Tenant) located on or in the Premises. Such insurance shall be in an amount equal to the full replacement cost of the aggregate of the foregoing and shall provide coverage comparable to the coverage in the standard ISO “All-Risk” or “Special” form, when such coverage is supplemented with the coverages required above. Property policy shall also include coverage for plate glass, where required by written contract.

Builders Risk insurance coverage may be provided by the general contractor on a blanket builders risk policy with limits adequate for the project, and evidencing the additional insureds as required in the Lease.

(2)    Liability Insurance. General Liability, Umbrella/Excess Liability, Workers Compensation and Auto Liability coverage as follows:

          (a)    General Liability $1, 000, 000 per occurrence

$1, 000, 000 personal & advertising injury

$2, 000, 000 products/completed operations aggregate

$2, 000, 000 general aggregate

The General Contractor is required to maintain, during the construction period and up to 3 years after project completion, a General Liability insurance policy, covering bodily injury, personal injury? property damage, completed operations, with limits to include a $1, 000, 000 limit for blanket contractual liability coverage and adding Landlord as additional insured as respects the project during construction and for completed operations up to 3 years after the end of the project. Landlord requires a copy of the ISO 20 10 11 85 Additional Insured endorsement, showing Landlord as an additional insured to the GC’s policy.

(b)    Auto Liability $1, 000, 000 combined single limit (Any Auto) for bodily injury and property damage, hired and non-owned cover.

       (c)    Workers Compensation Statutory Limits

                Employers Liability $1,000, 000 each accident

$1,000, 000 each employee

$1,000, 000 policy limit

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General Contractor shall ensure that any and all sub-contractors shall maintain equal limits of coverage for Workers Compensation/EL and collect insurance certificates verifying same.

      (d)     Umbrella/Excess Liability $3, 000, 000 per occurrence

$3, 000, 000 aggregate

(e)    Environmental Insurance - To the extent required by Landlord Contractors5 commercial general liability/umbrella insurance policy(ies) shall include Landlord and Landlord’s designees as additional insureds’, and shall include a primary non-contributory provision. Liability policy shall contain a clause that the insurer may not cancel or materially change coverage without first giving Landlord thirty (30) days prior written notice, except cancellation for non-payment of premium, in which ten (10) days prior written notice shall be required.

(3)    Deductibles. If any of the above insurances have deductibles or self-insured retentions, the Tenant and/or contractor (policy Named Insured) shall be responsible for the deductible amount.

All of the insurance policies required in this Exhibit D shall be written by insurance companies which are licensed to do business in the State where the property is located, or obtained through a duly authorized surplus lines insurance agent or otherwise in conformity with the laws of such state, with an A.M. Best rating of at least A and a financial size category of not less than VII. Tenant shall provide Landlord with certificates of insurance upon request, prior to commencement of the Tenant/contractor work, or within thirty (30) days of coverage inception and subsequent renewals or rewrites/replacements of any cancelled/non-renewed policies.

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Exhibit E

Form of Term Commencement Date Agreement

COMMENCEMENT DATE AGREEMENT

Cyteir Therapeutics, Inc. (“Tenant”) hereby certifies that it has entered into a lease with Related Beal (“Landlord”) dated as of August, 08, 2018 and verifies the following information as of the 8th day of August, 2018:

Address of Building:	99 Hayden Avenue, Lexington, Massachusetts
Number of Rentable Square Feet in Premises:
Commencement Date:	, 20
Rent Commencement Date:	, 20
Lease Termination Date:
Tenant’s Pro Rata Share:	3.97%
Billing Address for Tenant:
Attention:	Markus Renschlen MD
Telephone Number:	(    )
Federal Tax I.D. No.:	45 5429901

Tenant acknowledges and agrees that all improvements Landlord is obligated to make to the Premises, if any, have been completed to Tenant’s satisfaction, that Tenant has accepted possession of the Premises, and that as of the date hereof, there exist no offsets or defenses to the obligations of Tenant under the Lease.

TENANT:

By:

Name:	Markus Renschler, MD
Title:	President & CEO Hereunto duly authorized

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LANDLORD:

128 Spring Street Lexington, LLC

By:

Name:

Title:

Hereunto duly authorized

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Exhibit F

Construction Documents

1.    Preparation of Construction Documents. The Construction Documents shall include all architectural, mechanical, electrical and structural drawings and detailed specifications for the Tenant Work and shall show all work necessary to complete the Tenant Work including all cutting, fitting, and patching and all connections to the mechanical and electrical systems and components of the Building. Tenants leasing partial floors shall design entrances, doors and any other elements which visually integrate with the elevator lobbies and common areas in a manner and with materials and finishes which are compatible with the common area finishes for such floor. Landlord reserves the right to reject Construction Documents which in its reasonable opinion fail to comply with this provision. The Construction Documents shall include:

(a)    Major Work Information: A list of any items or matters which might require structural modifications to the Building, including the following:

(i) Location and details of special floor areas exceeding 150 pounds of live load per square foot;

(ii) Location and weights of storage files, batteries, HVAC units and technical areas;

(iii) Location of any special soundproofing requirements;

(iv) Existence of any extraordinary HVAC requirements necessitating perforation of structural members; and

(v) Existence of any requirements for heavy loads, dunnage or other items affecting the structure.

(b)    Plans Submission: Two (2) blackline drawings and one (1) CAD disk showing all architectural, mechanical and electrical systems, including cutsheets, specifications and the following:

CONSTRUCTION PLANS:

(1) All partitions shall be shown; indicate ratings of all partitions; indicate all non-standard construction and details referenced;

(2) Dimensions for partition shall be shown to face of stud; critical tolerances and ± dimensions shall be clearly noted;

(3) All doors shall be shown on and shall be numbered and scheduled on door schedule; indicate ratings of all doors;

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(4) All non-standard construction, non-standard materials and/or installation shall be explicitly noted; equipment and finishes shall be shown and details referenced; and

(5) All plumbing fixtures or other equipment requirements and any equipment requiring connection to Building plumbing systems shall be noted.

REFLECTED CEILING PLAN:

(1) Layout suspended ceiling grid pattern in each room, describing the intent of the ceiling working point, origin and/or centering; and

(2) Locate all ceiling-mounted lighting fixtures and air handling devices including air dampers, fan boxes, etc., lighting fixtures, supply air diffusers, wall switches, down lights, special lighting fixtures, special return air registers, special supply air diffusers, and special wall switches.

TELECOMMUNICATIONS AND ELECTRICAL EQUIPMENT PLAN:

(1) All telephone outlets required;

(2) All electrical outlets required; note non-standard power devices and/or related equipment;

(3) All electrical requirements associated with plumbing fixtures or equipment; append product data for all equipment requiring special power, temperature control or plumbing considerations;

(4) Location of telecommunications equipment and conduits; and

(5) Components and design of the Antennas (including associated equipment) as installed, in sufficient detail to evaluate weight, bearing requirements, wind-load characteristics, power requirements and the effects on Building structure, moisture resistance of the roof membrane and operations of pre-existing telecommunications equipment.

DOOR SCHEDULE:

(1) Provide a schedule of doors, sizes, finishes, hardware sets and ratings; and

(2) Non-standard materials and/or installation shall be explicitly noted.

HVAC:

(1) Areas requiring special temperature and/or humidity control requirements;

(2) Heat emission of equipment (including catalogue cuts), such as CRTs, copy machines, etc.;

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(3) Special exhaust requirements - conference rooms, pantry, toilets, etc.; and

(4) Any extension of system beyond demised space.

ELECTRICAL:

(1) Special lighting requirements;

(2) Power requirements and special outlet requirements of equipment;

(3) Security requirements;

(4) Supplied telephone equipment and the necessary space allocation for same; and

(5) Any extensions of tenant equipment beyond demised space.

(1) Remote toilets;

(2) Pantry equipment requirements;

(3) Remote water and/or drain requirements such as for sinks, ice makers, etc.; and

(4) Special drainage requirements, such as those requiring holding or dilution tanks.

ROOF:

Detailed plan of any existing and proposed roof equipment showing location and elevations of all equipment.

SITE:

Detailed plan, including fencing, pads, conduits, landscaping and elevations of equipment.

SPECIAL SERVICES:

Equipment cuts, power requirements, heat emissions, raised floor requirements, fire protection requirements, security requirements, and emergency power.

2.    Plan Requirements. The Construction Documents shall be fully detailed and fully coordinated with each other and with existing field conditions, shall show complete dimensions, and shall have designated thereon all points of location and other matters, including special construction details and finish schedules. All drawings shall be uniform size and shall incorporate the standard electrical and plumbing symbols and be at a scale of 1/8” = 1’0” or larger. Materials and/or installation shall be explicitly noted and adequately specified to allow for Landlord review, building permit application, and construction. All equipment and installations shall be made in accordance with standard materials and procedures unless a deviation outside of industry standards is shown on the Construction Documents and approved by Landlord. To the extent practicable, a concise description of products, acceptable substitutes, and installation procedures and standards shall be provided. Product cuts must be provided and special mechanical or electrical loads noted. Landlord’s approval of the plans, drawings, specifications or other submissions in respect of any work, addition, alteration or improvement to be undertaken by or on behalf of Tenant shall create no liability or responsibility on the part of Landlord for their completeness, design sufficiency or compliance with requirements of any applicable laws, rules or regulations of any governmental or quasi-governmental agency, board or authority.

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3.    Drawing and Document Production. Landlord shall provide Tenant with two (2) blackline drawings and one (1) CAD disk showing the Building and site outline, core walls and columns, together with corridor and demising wall location plans.

4.    Change Orders. The Construction Documents shall not be materially changed or modified by Tenant after approval by Landlord without the further approval in writing by Landlord, which approval shall not be unreasonably withheld or delayed. Landlord shall not be obligated to approve any change or modification of the Construction Documents which in Landlord’s sole opinion shall cause any additional cost or expense to Landlord for which Tenant has not agreed to reimburse Landlord.

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Exhibit G

Tenant’s List of Environmental Substances and Quantities Approved by Landlord

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Exhibit H

Plans and Specifications for Initial Tenant Improvements

[The Plans set forth on the attached Drawing Log]

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Exhibit I

Plan Showing Additional Space

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Exhibit J

Form of Letter of Credit

IRREVOCABLE STANDBY LETTER OF CREDIT NO.

DATE:

BENEFICIARY:

128 SPRING STREET LEXINGTON, LLC

c/o Related Beal

177 Milk Street

Boston, Massachusetts 02109

AS “LANDLORD”

APPLICANT:

AS “TENANT”

AMOUNT: US $                                (                                          AND 00/100 U.S. DOLLARS)

EXPIRATION DATE:                                     

LOCATION: AT OUR COUNTERS IN BOSTON, MASSACHUSETTS DEAR SIR/MADAM:

WE HEREBY ESTABLISH OUR IRREVOCABLE STANDBY LETTER OF CREDIT NO.                      IN YOUR FAVOR AVAILABLE BY YOUR DRAFT DRAWN ON US AT SIGHT IN THE FORM OF EXHIBIT “B” ATTACHED AND ACCOMPANIED BY THE FOLLOWING DOCUMENTS:

1.     THE ORIGINAL OF THIS LETTER OF CREDIT AND ALL AMENDMENT(S), IF ANY.

2.     A DATED CERTIFICATION FROM THE BENEFICIARY SIGNED BY AN AUTHORIZED OFFICER OR AGENT, FOLLOWED BY ITS DESIGNATED TITLE, STATING THE FOLLOWING:

(A)    “THE AMOUNT REPRESENTS FUNDS DUE AND OWING TO US FROM APPLICANT PURSUANT TO THAT CERTAIN LEASE BY AND BETWEEN BENEFICIARY, AS LANDLORD, AND APPLICANT, AS TENANT.”

OR

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(B)    “WE HEREBY CERTIFY THAT WE HAVE RECEIVED NOTICE FROM                              BANK THAT LETTER OF CREDIT NO.                          WILL NOT BE RENEWED, AND THAT WE HAVE NOT RECEIVED A REPLACEMENT OF THIS LETTER OF CREDIT FROM APPLICANT SATISFACTORY TO US AT LEAST THIRTY (30) DAYS PRIOR TO THE EXPIRATION DATE OF THIS LETTER OF CREDIT.”

THE LEASE AGREEMENT MENTIONED ABOVE IS FOR IDENTIFICATION PURPOSES ONLY AND IT IS NOT INTENDED THAT SAID LEASE AGREEMENT BE INCORPORATED HEREIN OR FORM PART OF THIS LETTER OF CREDIT.

OUR OBLIGATION UNDER THIS CREDIT SHALL NOT BE AFFECTED BY ANY CIRCUMSTANCES, CLAIM OR DEFENSE, REAL OR PERSONAL, OF ANY PARTY AS TO THE ENFORCEABILITY OF THE LEASE BETWEEN YOU AND TENANT, IT BEING UNDERSTOOD THAT OUR OBLIGATION SHALL BE THAT OF A PRIMARY OBLIGOR AND NOT THAT OF A SURETY, GUARANTOR OR ACCOMMODATION MAKER. IF YOU DELIVER THE WRITTEN CERTIFICATE REFERENCED ABOVE TO US, (I) WE SHALL HAVE NO OBLIGATION TO DETERMINE WHETHER ANY OF THE STATEMENTS THEREIN ARE TRUE, (II) OUR OBLIGATIONS HEREUNDER SHALL NOT BE AFFECTED IN ANY MANNER WHATSOEVER IF THE STATEMENTS MADE IN SUCH CERTIFICATE ARE UNTRUE IN WHOLE OR IN PART, AND (III) OUR OBLIGATIONS HEREUNDER SHALL NOT BE AFFECTED IN ANY MANNER WHATSOEVER IF TENANT DELIVERS INSTRUCTIONS OR CORRESPONDENCE TO WHICH EITHER (A) DENIES THE TRUTH OF THE STATEMENT SET FORTH IN THE CERTIFICATE REFERRED TO ABOVE, OR (B) INSTRUCTS US NOT TO PAY BENEFICIARY ON THIS CREDIT FOR ANY REASON WHATSOEVER.

PARTIAL AND MULTIPLE DRAWS ARE ALLOWED. EXCEPT AS EXPRESSLY SET FORTH HEREIN, THIS LETTER OF CREDIT MUST ACCOMPANY ANY DRAWINGS HEREUNDER FOR ENDORSEMENT OF THE DRAWING AMOUNT AND WILL BE RETURNED TO THE BENEFICIARY UNLESS IT IS FULLY UTILIZED.

DRAFT(S) AND DOCUMENTS MUST INDICATE THE NUMBER AND DATE OF THIS LETTER OF CREDIT.

THIS LETTER OF CREDIT SHALL BE AUTOMATICALLY EXTENDED FOR AN ADDITIONAL PERIOD OF ONE YEAR, WITHOUT AMENDMENT, FROM THE PRESENT OR EACH FUTURE EXPIRATION DATE UNLESS AT LEAST SIXTY (60) DAYS PRIOR TO THE THEN CURRENT EXPIRATION DATE WE NOTIFY YOU BY REGISTERED MAIL/OVERNIGHT COURIER SERVICE AT THE ABOVE ADDRESSES THAT THIS LETTER OF CREDIT WILL NOT BE EXTENDED BEYOND THE CURRENT EXPIRATION DATE. IN NO EVENT SHALL THIS LETTER OF CREDIT BE AUTOMATICALLY EXTENDED BEYOND SIX (6) MONTHS BEYOND LEASE EXPIRATION.

THIS LETTER OF CREDIT MAY BE TRANSFERRED WITHOUT COST TO THE BENEFICIARY, ONE OR MORE TIMES BUT IN EACH INSTANCE TO A SINGLE BENEFICIARY AND ONLY IN THE FULL AMOUNT AVAILABLE TO BE DRAWN UNDER THE LETTER OF CREDIT AT THE TIME OF THE TRANSFER AND ONLY BY THE ISSUING BANK UPON OUR RECEIPT OF THE ATTACHED “EXHIBIT A” DULY COMPLETED AND

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EXECUTED BY THE BENEFICIARY AND ACCOMPANIED BY THE ORIGINAL LETTER OF CREDIT AND ALL AMENDMENTS, IF ANY.

ALL DEMANDS FOR PAYMENT SHALL BE MADE BY PRESENTATION OF THE ORIGINAL APPROPRIATE DOCUMENTS PRIOR TO 10:00 A.M. E.S.T. TIME, ON A BUSINESS DAY AT OUR OFFICE (THE “BANK’S OFFICE”) AT:

                                                         , BOSTON, MASSACHUSETTS                             , ATTENTION:                              OR BY FACSIMILE TRANSMISSION AT: (617)                             ; AND SIMULTANEOUSLY UNDER TELEPHONE ADVICE TO: (617)                             , ATTENTION:                             WITH ORIGINALS TO FOLLOW BY OVERNIGHT COURIER SERVICE.

PAYMENT AGAINST CONFORMING PRESENTATIONS HEREUNDER SHALL BE MADE BY BANK DURING NORMAL BUSINESS HOURS OF THE BANK’S OFFICE WITHIN ONE (1) BUSINESS DAY AFTER PRESENTATION.

WE HEREBY AGREE WITH THE DRAWERS, ENDORSERS AND BONAFIDE HOLDERS THAT THE DRAFTS DRAWN UNDER AND IN ACCORDANCE WITH THE TERMS AND CONDITIONS OF THIS LETTER OF CREDIT SHALL BE DULY HONORED UPON PRESENTATION TO THE DRAWEE, IF NEGOTIATED ON OR BEFORE THE EXPIRATION DATE OF THIS CREDIT.

THIS LETTER OF CREDIT IS SUBJECT TO THE UNIFORM CUSTOMS AND PRACTICE FOR DOCUMENTARY CREDITS (2007 REVISION), INTERNATIONAL CHAMBER OF COMMERCE, PUBLICATION NO. 600.

  AUTHORIZED SIGNATURE   AUTHORIZED SIGNATURE

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EXHIBIT “A”

DATE:

TO:

RE: STANDBY LETTER OF CREDIT

NO.                 ISSUED BY

ATTN:

    L/C AMOUNT:

LADIES AND GENTLEMEN:

FOR VALUE RECEIVED, THE UNDERSIGNED BENEFICIARY HEREBY

IRREVOCABLY TRANSFERS TO:

(NAME OF TRANSFEREE)

(ADDRESS)

ALL RIGHTS OF THE UNDERSIGNED BENEFICIARY TO DRAW UNDER THE ABOVE LETTER OF CREDIT UP TO ITS AVAILABLE AMOUNT AS SHOWN ABOVE AS OF THE DATE OF THIS TRANSFER.

BY THIS TRANSFER, ALL RIGHTS OF THE UNDERSIGNED BENEFICIARY IN SUCH LETTER OF CREDIT ARE TRANSFERRED TO THE TRANSFEREE. TRANSFEREE SHALL HAVE THE SOLE RIGHTS AS BENEFICIARY THEREOF, INCLUDING SOLE RIGHTS RELATING TO ANY AMENDMENTS, WHETHER INCREASES OR EXTENSIONS OR OTHER AMENDMENTS, AND WHETHER NOW EXISTING OR HEREAFTER MADE. ALL AMENDMENTS ARE TO BE ADVISED DIRECT TO THE TRANSFEREE WITHOUT NECESSITY OF ANY CONSENT OF OR NOTICE TO THE UNDERSIGNED BENEFICIARY.

THE ORIGINAL OF SUCH LETTER OF CREDIT IS RETURNED HEREWITH, AND WE ASK YOU TO ENDORSE THE TRANSFER ON THE REVERSE THEREOF, AND FORWARD IT DIRECTLY TO THE TRANSFEREE WITH YOUR CUSTOMARY NOTICE OF TRANSFER.

SINCERELY,

(BENEFICIARY’S NAME)

SIGNATURE OF BENEFICIARY

J-4

SIGNATURE AUTHENTICATED

(NAME OF BANK)

AUTHORIZED SIGNATURE

J-5

EXHIBIT “B”

J-6

EX-10.2

Exhibit 10.2

FIRST AMENDMENT TO LEASE

This First Amendment to Lease (“First Amendment”) is executed as of the 15^th day of October, 2019, by and between 128 Spring Street Lexington, LLC, as landlord (“Landlord”) and Cyteir Therapeutics, Inc., as tenant (“Tenant”).

B A C K G R O U N D:

A.    Reference is made to a certain Lease between Landlord and Tenant dated August 8, 2018 (the “Lease”), pursuant to which Tenant is currently leasing from Landlord approximately 7,442 rentable square feet of space (the “Original Premises”) on portions of the 500 Level of Building A located at 99 Hayden Avenue, Lexington, Massachusetts. Capitalized terms not otherwise defined herein shall have the meaning ascribed to them in the Lease.

B.    Landlord and Tenant are the current holders, respectively, of the lessor’s and lessee’s interests in the Lease.

C.    Landlord and Tenant desire to amend the Lease in certain respects as provided herein.

A G R E E M E N T S:

NOW, THEREFORE, in consideration of the agreements set forth herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, Landlord and Tenant hereby agree, and amend the Lease, as follows:

1.    Premises. The Original Premises is located on the 500 Level of Building A. As of the Expansion Commencement Date (defined below), (i) approximately 7,194 rentable square feet on the 400 Level of Building A as more particularly shown on the attached Exhibit A (the “Expansion Premises”), shall be added to and incorporated into the Original Premises, subject to the terms of this First Amendment (the Original Premises and the Expansion Premises being collectively referred to as the “Premises”),(ii) the Premises shall consist of a total of approximately 14,636 rentable square feet, and (iii) Tenant’s Pro Rata Share shall be increased to 7.79% (subject to Section 4.06 of the Lease); provided, however, that while the Permitted Uses for the Original Premises shall remain as set forth in the Lease, the Permitted Uses with respect to the Expansion Premises shall be limited to general office, research and laboratory use(s) (including research and development, but not as a vivarium or for the testing of animals) to the extent permitted by applicable zoning ordinances.

Except as specifically set forth in this First Amendment, from and after the Expansion Commencement Date, the Expansion Premises shall be deemed part of the Premises for all purposes, including, but not limited to, the Term set forth in Section 3.01 of the Lease and the Right to Extend set forth in Section 3.03 of the Lease.

2.    Delivery. Tenant shall accept the Expansion Premises as of the date the Initial Expansion Improvements are Substantially Complete (the “Expansion Premises Commencement Date”) which shall include (a) the roof and all Core Building Systems relating thereto (i) in good working condition and (ii) suitable for laboratory use, (b) the HVAC (but not any Tenant’s HYAC Unit) in good working condition, (c) and otherwise in “as-is” condition. Tenant acknowledges that except as expressly set forth herein, neither Landlord nor any person acting under Landlord has made any representation a.5 to the condition of the Property or the suitability of the Property for Tenant’s intended use. By occupying the Expansion Premises, Tenant shall be deemed to have accepted the Expansion Premises in their condition as of the date of such occupancy and Landlord shall be deemed to have completed all of its obligations under this Section 2.

3.    Initial Tenant Improvements for Expansion Premises.

a. Tenant shall promptly provide Landlord with all necessary information regarding Tenant’s space planning needs for the Bxpansio11 Premises for Landlord’s approval, such approval shall be subject to the standard set forth in Lease Section 10.05(a) (the “Initial Expansion Improvements”), which improvements shall be based upon and limited to the preliminary scope plan attached hereto as Exhibit B. Following Landlord’s approval of the final scope of Initial Expansion Improvements, Landlord shall cause space plans and specifications (“Expansion Plans and Specifications”) therefore to be prepared, a copy of which shall be delivered to Tenant The Initial Expansion Improvements shall not include Tenant’s furniture, trade fixtures, equipment and personal property and are limited to the fit-up construction as generally laid out and specified on the Expansion Plans and Specifications. Tenant acknowledges that the Initial Expansion Improvements, except as expressly provided in the Expansion Plans and Specifications, will be substantially designed and constructed to the general quality of the design and construction of the Building and in accordance with Landlord’s building standards for the Building.

b. Tenant agrees that Landlord shall have no obligation to make any material changes to the Plans and Specifications requested by Tenant, provided, however, to the extent Landlord agrees to any changes whether material or immaterial, Tenant agrees that any additional actual cost to Landlord, in excess of the Expansion Allowance resulting from such approved changes shall be the responsibility of Tenant and shall be paid in full by Tenant to Landlord within ten (10) business days of billing therefor by Landlord; and Tenant agrees that if any such changes do result in delay in Substantial Completion, same shall be deemed a Tenant Delay.

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c. Landlord shall proceed, using reasonable efforts, to obtain all necessary permits and approvals for the construction of the Initial Expansion Improvements, to engage a contractor or construction manager to perform or supervise the construction and to proceed to construct the Initial Expansion Improvements in substantial conformance with the Expansion Plans and Specifications. Landlord reserves the right to make changes and substitutions to the Expansion Plans and Specifications in connection with the construction of the Initial Expansion Improvements, provided same do not materially adversely modify the Expansion Plans and Specifications or the schedule or delivery of the Initial Expansion Improvements. In no event shall Landlord be liable to Tenant for any failure to Substantially Complete the Initial Expansion Improvements on any specified date, nor shall such failure give rise to any default or other remedies under this Lease or at law or equity; provided, however, in the event the Expansion Completion Date (as defined in subsection (d), below) has not occurred on or before May 1, 2020 (as such date shall be extended due to Tenant Delay or Force Majeure), then Tenant shall have the right to void this First Amendment by giving notice to Landlord of Tenant’s desire to do so by May 8, 2020; and, upon the giving of such notice, the Term of this Lease shall, unless the Expansion Completion Date occurs within thirty (30) days after Landlord’s receipt of such notice, this First Amendment shall be void and of no further force or effect as of the date that is thirty (30) days after Landlord’s receipt of such notice from Tenant, and neither party sha11 have any further liability or obligation on the part of either party with respect thereto.

d. The Initial Expansion Improvements shall be deemed “Substantially Complete” on the date (the “Expansion Completion Date”) Tenant receives notice from Landlord that Landlord bas received a certificate of occupancy (temporary or permanent) or a fully- signed off building permit for the Expansion Premises issued by the Town of Lexington (the “Certificate of Occupancy”). Notwithstanding the foregoing, if any delay in the Substantial Completion of the Initial Expansion Improvements by Landlord is due to Tenant Delays, then the Expansion Completion Date shall be deemed to be the date (as set forth in a written notice from Landlord to Tenant) the Initial Expansion Improvements would have been Substantially Complete, if not for such Tenant Delays, as reasonably determined by Landlord. “Tenant Delays” shall have the same meaning as set forth in the Lease, but substituting (i) “Expansion Plans and Specifications” for “Plans and Specifications” and (ii) “Initial Expansion Improvements” for “Initial Tenant Improvements” If as a result of Tenant Delays the Initial Expansion Improvements are deemed Substantially Complete pursuant to the foregoing, but the Expansion Premises are not in fact actually ready for Tenant’s occupancy, Tenant shall not be entitled to take possession of the Expansion Premises for until the Expansion Premises are in fact actually ready for such occupancy.

e. Within seven (7) business days after the Expansion Completion Date, Landlord and Tenant shall confer and create a specific list of any defects or incomplete remaining items of work with respect to the Initial Expansion Improvements (a “Punchlist”), Landlord shall complete such Punchlist items with reasonable diligence and Landlord shall have access to the Expansion Premises for such purposes. Except with respect to the items contained in the Punchlist, as of the Expansion Completion Date Tenant shall be deemed satisfied with the Initial Expansion Improvements, Landlord shall be deemed to have completed all of its obligations under this Section 3, and Tenant shall have no claim that Landlord has failed to perform in full its obligations hereunder.

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f. Landlord shall pay the costs and expenses incurred by Landlord in connection with the performance and completion of the Initial Expansion Improvements in an amount not to exceed $323,730.00 (based on $4S.00 multiplied by 7,194 rentable square feet of the Expansion Premises) (the “Expansion Allowance”)and this shall be Landlord’s maximum contribution to the cost of constructing and installing the Initial Expansion Improvements. Landlord may include within the Expansion Allowance all reasonable, costs and expenses incurred by or on behalf of Landlord in connection with the Initial Expansion Improvements including without limitation, all design, review, permitting, bid preparation and bid review, construction, materials and supplies, and including a construction or project management fee payable to Landlord of three percent (3%) of the costs of the Initial Expansion Improvements. Landlord shall have no separate or additional obligation to pay Tenant the Improvement Allowance. Tenant shall be responsible for and promptly (but in no event longer than ten (10) days after request therefor) pay directly or pay to Landlord for, as appropriate, and indemnify and reimburse Landlord from and against, any actual costs of the Initial Expansion Improvements that are in excess of the Expansion Allowance including, without limitation, such costs over and above the Expansion Allowance necessary to complete the Initial Expansion Improvements as set forth in the Expansion Plans and Specifications, costs resulting from the Tenant’s upgrades from building standard construction materials or Tenant’s upgrades or changes to the Initial Expansion Improvements or any plans or specifications relating thereto. Landlord shall have the same rights and remedies which Landlord has upon the nonpayment of Base Rent and other charges due under this Lease for nonpayment of any amounts which Tenant is required to pay to Landlord or Landlord’s contractor in connection with the Initial Expansion Improvements or in connection with any construction in the Expansion Premises performed for Tenant by Landlord, Landlord’s contractor or any other person, firm or entity. Except for the Initial Expansion Improvements and any repairs expressly required to be made by Landlord under this Lease. Landlord shall have no obligation to perform any work or construction to make the Expansion Premises fit for use and occupation or for Tenant’s particular purpose or to make them acceptable to Tenant.

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g. In addition to the Expansion Allowance, upon the full use of the Expansion Allowance as provided herein, Landlord will make available to Tenant an additional allowance in an amount not to exceed $107.910.00 (based on $15.00 multiplied by 7,194 rentable square feet of the Expansion Premises) (the “Additional Expansion Allowance”), subject to repayment with interest as provided herein. The Additional Expansion Allowance shall be utilized for the same purposes of the Expansion Allowance and paid (and repaid) as provided below pursuant to the terms and conditions hereof. Notwithstanding anything to the contrary set forth in this Lease, all amounts disbursed or advanced under the Additional Expansion Allowance shall (together with interest as set forth below) be repaid to Landlord as Additional Rent on the following terms and conditions follows:

i. Interest on the principal balance of the Additional Expansion Allowance from time to time outstanding shall accrue from the Expansion Premises Commencement Date at the rate of eight percent (8%) per year. Interest shall be calculated on the basis of a 360-day year times the actual number of days elapsed.

ii. Until the first (1st) day of the month following the month in which the Expansion Premises Commencement Date shall have occurred (the “Expansion Allowance Conversion Date”), interest only on the principal balance of the Additional Expansion Allowance shall be payable monthly in arrears on the first (1st) day of each month.

iii. From and after the Expansion Allowance Conversion Date. principal and interest on the principal balance of the Additional Expansion Allowance shall be payable, as Additional Rent, in arrears on the first (1st) day of each month in equal monthly installments and in a manner such that the entire principal and interest shall be paid by no later than the last day of the Initial Tenn.

iv. Tenant may prepay the outstanding balance of the Additional Expansion Allowance, in whole or in part, and any accrued interest thereon; at any time, without premium or penalty.

h. All components of the Initial Expansion Improvements shall be part of the Building. except only for such items as Landlord shall designate in writing to be removed by Tenant on the termination of this Lease, which notice shall be delivered to Tenant simultaneously with the approval of the Expansion Plans and Specifications.

i. This First Amendment is subject to Landlord obtaining all permits, licenses and approvals necessary to allow Landlord to construct the Initial Expansion Improvements and obtain a Certificate of Occupancy with respect thereto; and if despite Landlord’s commercially reasonable efforts Landlord shall be unable to obtain such permits, license or approvals on or before the six (6) month anniversary of this First Amendment, or Certificate of Occupancy on or before June 15, 2020, and is therefore unable to commence or complete the Initial Expansion Improvements, then this First Amendment may be rendered void and of no further force or effect by Landlord or Tenant by written notice to the other,. and neither party shall have any further liability or obligation on the part of either party with respect thereto.

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4.    Base Rent. Tenant shall continue to pay Base Rent for the Premises to Landlord in the manner and at the times set forth in Section 4.01 of the Lease, in advance, without demand, notice, deduction or set off, (i) with respect to the Original Premises at the rates set forth in Article 1 of the Lease and (ii) with respect to the Expansion Premises, commencing on the earlier to occur of (a) the date on which Tenant commences business operations in all or any portion of the Expansion Premises or (b) the Expansion Completion Date (the “Expansion Premises Rent Commencement Date”), at the following rates:

Period	Annual RSF		Annual Base Rent		Monthly Installment
Expansion Premises Rent Commencement Date- end of the first Expansion Lease Year	$	46.00	$	330,924.00	$	27,577.00
Expansion Lease Year 2	$	47.38	$	340,851.72	$	28,404.31
Expansion Lease Year 3	$	48.80	$	351,067.20	$	29,255.60
Expansion Lease Year 4	$	50.26	$	361,570.44	$	30,130.87
Expansion Lease Year 5 (if applicable)	$	51.77	$	372,433.38	$	31,036.12

For purposes of this Section 4, the term “Expansion Lease Year” shall refer to a period of consecutive 12 months, the first commencing on the Expansion Premises Rent Commencement Date and each successive 12 month period during the Term (except for the last Expansion Lease Year, which shall end on the expiration date of the Term).

Base Rent for the Extension TeI111, if exercised, shall be as provided in Section 3.03(b) of the Lease as to both the Original Premises and the Expansion Premises.

5.    Additional Rent. Tenant shall continue to pay Additional Rent, including, without limitation, Tenant’s Pro Rata Share of Taxes, Utilities, Insurance premiums, and Operating Expenses; provided, however, that from and after the Expansion Commencement Date, Tenant’s Pro Rata Share shall be as set forth in Section 1 of this First Amendment.

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6.    Security Deposit. On or before the Expansion Commencement Date, Tenant shall increase the Letter of Credit Amount from $143,258.50 to $255,317.10 by providing Landlord with either (i) a substitute letter of credit in the increased amount in exchange for the existing letter(s) of credit which Landlord is then holding or (ii) an amendment to the existing letter(s) of credit then held by Landlord, in either case in form and substance reasonably acceptable to Landlord and which is accepted by Landlord in writing. The reduction schedule set forth in Article 15 of the Lease is hereby deleted in its entirety and replaced with the following:

Reduction Date	New Reduced Letter of Credit Amount
November 1, 2020	$	204,253.68
November 1, 2021	$	153,190.26

Except as expressly set forth in this First Amendment, such letter(s) of credit shall be subject to Article 15 of the Lease.

7.    Right of First Offer. From and after the Expansion Premises Commencement Date, the term “Additional Space” as defined in Section 2.02 of the Lease shall be expanded to include contiguous spaces in Buildings A and Bas shown on the four (4) plans comprising Exhibit C, attached hereto (the “New Additional Spaces”). Tenant understands that its rights under Section 2.02 of the Lease as to the New Additional Spaces are and shall be subject and subordinate to any options to lease or any rights of first negotiation, first offer or first refusal to lease granted to other tenants of the Building prior to the date of execution and delivery of this First Amendment.

8.    Signage. Landlord, at Landlord’s cost (which costs may be included in Operating Expenses), shall provide Tenant with identification on existing multi-tenant signs or directories in Building A and on other existing common area signage, as appropriate. Such signs will be consistent with standard Building signage and will conform to local regulations.

9.    Roof Rights. Tenant shall have the same license and rights and obligations with respect to the roof of Building A to benefit the Expansion Premises as are set forth in Section 2.02 of the Lease.

10.    Successors: Conflicts. This First Amendment shall be binding upon the parties and their respective successors and assigns. To the extent the terms and conditions of the Lease expressly conflict with or are expressly inconsistent with this First Amendment, the terms and conditions of this First Amendment shall control.

11.    Parking. Tenant shall continue to have the appurtenant right to unreserved parking spaces, as more particularly described in Section 2.0l(d) of the Lease, calculated at the ratio of 2.5 parking spaces per 1,000 per rentable square feet of the Premises (as expanded by this First Amendment).

12.    Loading Dock. Tenant shall continue to have the appurtenant right to use the loading dock, as set forth in Section 2.0I(b) of the Lease.

13.    Brokers. Tenant represents and warrants to Landlord that it has not directly or indirectly dealt, with respect to this First Amendment, with any broker or had its attention called to the Expansion Premises or other space to let at the Property, etc. by anyone other than Newmark Knight Frank. Tenant agrees to defend, exonerate and save harmless and indemnify Landlord and anyone claiming by, through or under Landlord against any claims for a commission arising out of the execution and delivery of this First Amendment or out of negotiations between Landlord and Tenant with respect to the leasing of other space at the Property. Landlord is responsible for paying all commissions to Newmark Knight Frank pursuant to separate agreement(s) therewith.

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14.    Miscellaneous. Except as expressly modified herein, the Lease shall remain unmodified and in full force and effect. The provisions of this First Amendment shall be binding upon and shall inure to the benefit of Landlord and Tenant and their respective legal representatives, successors and assigns. Any signature delivered by a party by facsimile or electronic transmission shall be deemed to be an original signature to this First Amendment.

15.    Counterparts and Electronic Execution. This First Amendment may be executed in counterparts and shall constitute an agreement binding on all parties notwithstanding that all parties are not signatories to the original or the same counterpart provided that all parties are furnished a copy or copies thereof reflecting the signature of all parties. Transmission of a facsimile or by email of a Portable Document Format (PDF) (or similar electronic counterpart including DocuSign) copy of the signed counterpart of this First Amendment shall be deemed the equivalent of the delivery of the original, and any party so delivering a facsimile or PDF (or similar electronic counterpart) copy of the signed counterpart of this First Amendment by email transmission shall in all events deliver to the other party an original signature promptly upon request. In addition. this First Amendment, any other document necessary for the consummation of the transaction contemplated by this First Amendment may be accepted, executed or agreed to through the use of DocuSign or other means of electronic signature acceptable to Landlord and in accordance with the Electronic Signatures in Global and National Commerce Act (“ E-Sign Act” ), Title 15, United States Code, Sections 7001 et seq., the Uniform Electronic Transaction Act(“ UETA”) and any applicable state law. Any document accepted, executed or agreed to in conformity with such laws will be binding on each party as if it were physically executed. The exchange of executed copies of this First Amendment or any subsequent amendment or modification hereof by facsimile, DocuSign or PDF (or other electronic means) transmission shall constitute effective execution and delivery of this First Amendment or such amendment or modification. as applicable, as to the parties for all purposes.

[Signature Page to Follow]    

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IN WITNESS WHEREOF the parties hereto have executed this First Amendment to Lease in multiple copies, each to be considered an original hereof, as a sealed instrument on the date first written above    

LANDLORD:		TENANT:
128 Spring Street Lexington, LLC		Cyteir Therapeutics, Inc.
By:	/s/ Stephen N. Faber	By:	/s/ Markus Renschler
Name: Stephen N. Faber		Name: Markus Renschler, MD
Title: Authorized Signatory		Title: President & CEO, Cyteir Therapeutics Inc.
		Hereunto Duly Authorized

Exhibit A

PLAN SHOWING THE EXPANSION PREMISES

This plan is to show the location of the Expansion Premises only and may not depict the current condition of the Expansion Premises. Any furniture shown hereon is for illustrative purposes only and shall not be included with delivery of the Expansion Premises.

Exhibit C

PRELIMINARY SCOPE PLAN

Exhibit C

ADDITIONAL SPACES

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EX-21.1

Exhibit 21.1

Subsidiary	Location
Cyteir Securities Corporation	Massachusetts