bntx-20251231

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 20-F

☐REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT

OF 1934

☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2025

☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Commission file number: 001-39081

BioNTech SE

(Exact name of Registrant as specified in its charter)

Federal Republic of Germany

(Jurisdiction of incorporation or organization)

An der Goldgrube 12

D-55131 Mainz

Germany

(Address of principal executive offices)

Prof. Ugur Sahin, M.D.

c/o BioNTech SE

An der Goldgrube 12

D-55131 Mainz

Germany

+49 6131-9084-0 (Tel), +49 6131 9084-390 (Fax), info@biontech.de (E-mail)

(Name, Telephone, E-mail and/or Facsimile number and Address of Company Contact Person)

Securities registered or to be registered, pursuant to Section 12(b) of the Act


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
American Depositary Shares, each Representing one ordinary share	BNTX	The Nasdaq Stock Market LLC
Ordinary shares, no par value, with a notional amount attributable to each ordinary share of €1*	—	The Nasdaq Stock Market LLC*

Securities registered or to be registered pursuant to Section 12(g) of the Act: None

Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act: None

Indicate the number of outstanding shares of each of the issuer’s classes of capital stock or common stock as of the close of business

covered by the annual report.

Ordinary shares, no par value, with a notional amount attributable to each share of €1 outstanding up until March 3, 2025, the most recent

practicable date, no par value: 239,970,804

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☒ No ☐

If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or

15(d) of the Securities Exchange Act of 1934. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been

subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to

Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was

required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or an emerging growth

company. See the definitions of “large accelerated filer,” “accelerated filer,” and “emerging growth company” in Rule 12b-2 of the Exchange

Act.


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

If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, 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 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its

internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public

accounting firm that prepared or issued its audit report. ☒

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant

included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based

compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:


U.S. GAAP ☐		International Financial Reporting Standards as issued by the International Accounting Standards Board ☒		Other ☐

If “Other” has been checked in response to the previous question indicate by check mark which financial statement item the registrant has

elected to follow. Item 17 ☐ Item 18 ☐

If this is an annual report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).

Yes ☐ No ☒

* Listed not for trading or quotation purposes, but only in connection with the registration of American Depositary Shares representing such ordinary shares

pursuant to the requirements of the Securities and Exchange Commission. The American Depositary Shares are registered under the Securities Act of 1933, as

amended, pursuant to a separate registration statement on Form F-6 (File No. 333-233898).

Annual Report on Form 20-F for the year ended December 31, 2025


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GENERAL INFORMATION

In this Annual Report on Form 20-F, or the Annual Report, “BioNTech,” the “Group,” the “Company,” “we,” “us,”

and “our” refer to BioNTech SE and its consolidated subsidiaries, except where the context otherwise requires.

In response to the fact that our consolidated financial statements are published in Euro, the selected

consolidated financial data is presented in Euro as well. Amounts in U.S. dollar are translated into Euro using the

exchange rates as per period end or average exchange rates for the periods indicated as published by the

German Central Bank (Deutsche Bundesbank).

All references in this Annual Report to “$” mean U.S. dollars and all references to “€” mean Euros.

This Annual Report contains references to our trademarks and to trademarks belong to other entities. Solely for

convenience, trademarks and trade names referred to, 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 their

respective owners will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend

our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or

sponsorship of us by, any other companies.

Our trademark portfolio includes, but is not limited to, BioNTech, Comirnaty, BioNTainer, FixVac, RiboCytokine,

and RiboMab, including logo versions of some of these trademarks. Brand names appearing in italics throughout

this report are trademarks owned by BioNTech. All other trademarks are the property of their respective owners.

Annual Report on Form 20-F for the year ended December 31, 2025


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CAUTIONARY STATEMENT REGARDING

FORWARD-LOOKING STATEMENTS

This Annual Report contains forward-looking statements concerning our business, operations and financial

performance and condition as well as our plans, objectives and expectations for our business operations and

financial performance and condition. Any statements that are not of historical facts may be deemed to be

forward-looking statements. Many of the forward-looking statements contained in this Annual Report can be

identified by the use of forward-looking words such as “believes”, “estimates”, “anticipates”, “expects”, “plans”,

“intends”, “may”, “could”, “might”, “will”, “should”, “aims” or other similar expressions that convey uncertainty of

future events or outcomes.

These forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and

other factors that could cause our actual results of operations, financial condition, liquidity, performance,

prospects, opportunities, achievements or industry results, as well as those of the markets we serve or intend to

serve, to differ materially from those expressed in, or suggested by, these forward-looking statements. These

forward-looking statements are based on assumptions regarding our present and future business strategies and

the environment in which we expect to operate in the future. Important factors that could cause those differences

include, but are not limited to:

–the extent to which COVID-19 vaccines continue to be necessary in the future and any effects of reduced

demand for our COVID-19 vaccine, including the write-down of inventory and costs relating to contract

manufacturing production capacities that become redundant or unutilized;

–our expected revenues and net profit related to sales of our COVID-19 vaccine (also referred to as Comirnaty

in the United States and in the European Union to the extent authorized for use), respectively, in territories

controlled by our collaboration partners, particularly for those figures that are derived from preliminary

estimates provided by our partners;

–the initiation, timing, progress, results, and cost of our research and development programs and our current

and future preclinical studies and clinical trials, including statements regarding: the timing of initiation and

completion of studies or trials and related preparatory work, the period during which the results of the trials will

become available, and our research and development programs;

–our pricing and coverage negotiations for our COVID-19 vaccine with governmental authorities, private health

insurers and other third-party payors after our initial sales to national governments;

–competition from other COVID-19 vaccines or related to our other product candidates, including those with

different mechanisms of action and different manufacturing and distribution constraints, on the basis of,

among other things, efficacy, cost, convenience of storage and distribution, breadth of approved use, safety,

side-effect profile and durability of immune response;

–the timing and ability of us and our collaborators to obtain regulatory approval for our COVID-19 vaccine and

our product candidates, and to commercialize our approved and investigational product candidates, if

approved;

–the pricing and reimbursement of our COVID-19 vaccine and our product candidates, if approved;

Annual Report on Form 20-F for the year ended December 31, 2025


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–the rate and degree of market acceptance of our COVID-19 vaccine and our product candidates, if approved;

–our ability to identify research opportunities and discover and develop product candidates;

–our ability to utilize our resources on-hand and to focus on the development of product candidates that will

maximize shareholder value and our corporate pillars;

–our measures anticipated to be taken in connection with our strategic vision, including estimated FTE

increases and decreases;

–the ability and willingness of our third-party collaborators to continue research and development activities

relating to our product candidates;

–our expectations regarding the size of the patient populations for our product candidates, if approved for

commercial use;

–unforeseen safety issues and claims for personal injury or death arising from the use of our COVID-19 vaccine

and other products and product candidates developed or manufactured by us;

–our estimates of our expenses, future revenue and capital requirements and our needs for or ability to obtain

additional financing;

–our ability to identify, recruit and retain key personnel;

–our and our collaborators’ ability to protect and enforce our intellectual property protection for our proprietary

and collaborative product candidates, our ability to protect and defend against potential claims of others'

intellectual property, and the scope of such protection;

–the development of and projections relating to our competitors or our industry;

–the amount of and our ability to use net operating losses and research and development credits to offset

future taxable income;

–our ability, and that of our collaboration partners, as applicable, to manage development and expansion;

–regulatory developments in the United States and foreign countries;

–political uncertainty;

–our ability to effectively scale our production capabilities and manufacture our products, including our

COVID-19 vaccine, and our product candidates;

–our expectations with respect to the timing and amount of any dividends and any potential repurchases of our

outstanding American Depositary Shares, or ADSs;

–our expectations regarding the timing of customer payments for delivered COVID-19 vaccine;

–our ability to implement, maintain and improve effective internal controls; and

–other factors not known to us at this time.

The preceding list is not intended to be an exhaustive list of all of our forward-looking statements. The forward-

looking statements contained in this Annual Report speak only as of the date of this report, and unless otherwise

Annual Report on Form 20-F for the year ended December 31, 2025


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PART I

Item 1. Identity of Directors, Senior Management and Advisers

Not applicable.

Item 2. Offer Statistics and Expected Timetable

Not applicable.

Item 3. Key Information

A. [Reserved]

B. Capitalization and Indebtedness

Not applicable.

C. Reasons for the Offer and Use of Proceeds

Not applicable.

D. Risk Factors

Our business is subject to various risks, including those described below. You should consider carefully the risks

and uncertainties described below and in our future filings. If any such risks are realized, our business, financial

condition, results of operations and prospects could be materially and adversely affected. Additionally, risks and

uncertainties not currently known to us or that we currently deem to be immaterial also may materially adversely

affect our business, financial condition, results of operations and/or prospects.

Risk Factor Summary

–Our business is dependent on the successful development, regulatory approval and commercialization of new

medicinal product candidates based on our technology platforms, particularly our oncology assets including

BNT327 and our antibody-drug conjugate, or ADC, clinical assets. If we and our collaborators are unable to

obtain approval for and to effectively commercialize our product candidates for the treatment of patients in

their intended indications, our business would be significantly harmed.

–We are developing product candidates and services, including our oncology pipeline and ADC product

candidates, in an environment of rapid technological and scientific change, including evolving standards of

care, and our failure to effectively compete would prevent us from achieving significant market penetration.

Most of our competitors have significantly greater resources than we do and we may not be able to compete

successfully.

–Our product candidates may not work as intended, may cause undesirable effects or may have other

properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved

label, or result in significant negative consequences following marketing approval, if any.

Annual Report on Form 20-F for the year ended December 31, 2025


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–Clinical development involves a lengthy and expensive process with an uncertain outcome, and delays can

occur for a variety of reasons outside of our control. Clinical trials of our product candidates may be delayed,

and certain programs may never advance in the clinic or may be more costly to conduct than we anticipate,

and we may have difficulty recruiting patients to participate in clinical trials, any of which can affect our ability

to fund our company and would have a material adverse impact on our business.

–If we are not successful in discovering, developing and commercializing additional product candidates beyond

our current portfolio, our ability to expand our business and achieve our strategic objectives would be

impaired.

–Demand for our COVID-19 vaccine, though difficult to predict, is expected to continue to decrease in the near

future. Changing market dynamics, including as a result of government policy and public sentiment, will impact

our revenue, which currently depends heavily on sales of our COVID-19 vaccine, and result in challenges

relating to production of our COVID-19 vaccine.

–Our reported revenue is partially based on preliminary estimates of COVID-19 vaccine sales and costs from

Pfizer Inc., or Pfizer, that are likely to change in future periods, which may impact our reported financial

results.

–Other companies or organizations may challenge our intellectual property rights or may assert intellectual

property rights that prevent us from developing and commercializing our COVID-19 vaccine or our product

candidates and other technologies, or that negatively affect our results of operations.

–Even if we obtain regulatory approval for our product candidates, the products may not gain the market

acceptance among physicians, patients, hospitals, treatment centers and others in the medical community

necessary for commercial success.

–Our operating results may fluctuate significantly, which makes our future operating results difficult to predict. If

our operating results fall below expectations, the price of the ADSs representing our shares could decline.

–If we identify material weaknesses in our internal control over financial reporting and fail to remediate such

material weaknesses, we may not be able to report our financial results accurately or to prevent fraud.

–As a “foreign private issuer,” we are exempt from a number of rules under U.S. securities laws, as well as

Nasdaq rules, and we are permitted to file less information with the Securities and Exchange Commission, or

the SEC, than U.S. companies. This may limit the information available to holders of the ADSs and may make

our ordinary shares and the ADSs less attractive to investors.

–Our approved product and product candidates are based on novel technologies and they may be complex and

difficult to manufacture. We may encounter difficulties in manufacturing, product release, shelf life, testing,

storage, supply chain management or shipping. If we or any of the third-party manufacturers we work with

encounter such difficulties, our ability to supply materials for clinical trials or any approved product could be

delayed or stopped.

–If our efforts to obtain, maintain, protect, defend and/or enforce the intellectual property related to our

COVID-19 vaccine or our product candidates and technologies are not adequate, we may not be able to

compete effectively in our market.

–We have experienced and may continue to experience significant volatility in the market price of the ADSs

representing our ordinary shares.

Annual Report on Form 20-F for the year ended December 31, 2025


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–Our principal shareholders and management own a significant percentage of our ordinary shares and will be

able to exert significant control over matters subject to shareholder approval.

Risks Related to our Business

Our business is dependent on the successful development, regulatory approval and commercialization

of new medicinal product candidates based on our technology platforms, particularly our oncology

assets including BNT327 and our antibody-drug conjugate, or ADC, clinical assets. If we and our

collaborators are unable to obtain approval for and to effectively commercialize our product candidates

for the treatment of patients in their intended indications, our business would be significantly harmed.

Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is

expensive, time-consuming and uncertain, and we may not be able to obtain full approvals, or may only obtain

partial approvals, in the requested indication for the commercialization of product candidates we may develop.

Any product candidates we may develop and the activities associated with their development and

commercialization, including design, testing, manufacture, recordkeeping, labeling, storage, approval,

advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and by

comparable global health authorities. To obtain the requisite regulatory approvals required to commercialize any

of our product candidates, we and our collaborators must demonstrate through extensive preclinical studies and

clinical trials that our product candidates are safe and effective for their intended use in the relevant target

population. Successful completion of clinical trials is a prerequisite to submitting a biologics license application,

or BLA, or a new drug application, or NDA, to the FDA, a Marketing Authorization Application, or MAA, to the

EMA, and similar marketing applications to comparable global regulatory authorities, for each product candidate

and, consequently, the ultimate approval and commercial marketing of any product candidates.

Failure to obtain marketing approval for a product candidate will prevent us from commercializing the product

candidate in a given jurisdiction. Although our COVID-19 vaccine has received emergency use authorization

and/or regulatory approvals in certain countries, it is possible that none of our other product candidates, or any

product candidates we may seek to develop in the future, will ever obtain regulatory approval. We have limited

experience in filing and supporting the applications necessary to gain marketing approvals and may need to rely

on third-party contract research organizations, or CROs, regulatory consultants or collaborators to assist us in

this process. We expect to submit initial BLAs/MAAs for our product candidates in the United States, the

European Union and in other countries globally. In some of these jurisdictions, mRNA-based medicinal products

may be classified in different ways and may be subject to specific requirements. Securing regulatory approval

requires the submission of extensive quality, preclinical and clinical data and supporting information to the

various regulatory authorities for each therapeutic indication to establish the product candidate’s safety and

efficacy. 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. Clinical

benefit and risk are regularly assessed during development, and any new medicinal product we develop may

turn out to be insufficiently, i.e., not clinically meaningfully, effective, or may prove to have unacceptable adverse

effects, or other characteristics that may preclude our obtaining marketing approval or prevent or limit

commercial use.

The process of obtaining marketing approvals in the United States, the European Union and elsewhere is

expensive, and if additional clinical trials are required, may take many years. Timing can vary substantially based

upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Changes

in marketing approval policies and standards of care 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. The FDA, EMA and comparable

regulatory authorities in other countries have substantial discretion in the approval process and may refuse to

accept any application or may decide that the data are insufficient for approval and require additional preclinical,

clinical or other trials. In addition, varying interpretations of the data obtained from preclinical and clinical testing

Annual Report on Form 20-F for the year ended December 31, 2025


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could delay, limit or prevent marketing approval of a product candidate. 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. Additional delays or non-approval may result if an FDA panel of experts, referred to as

an Advisory Committee, or other regulatory authority recommends non-approval or restrictions on approval. For

example, the FDA’s approval of our LP.8.1-adapted monovalent COVID-19 vaccine is in a narrower population

than our previous variant-adapted vaccines. In addition, we may experience delays or rejections based upon

additional government regulation from future legislation or administrative action, or changes in regulatory agency

policy during the period of product development, clinical trials, and the review process. Officials appointed by the

U.S. presidential administration to oversee the agencies involved with approval of drugs and biologics may seek

to change regulatory requirements for approval or the approach to reviewing applications. Together with changes

of regulatory policy priorities and allocated resources, this could cause further delays, expense or non-approvals.

Regulatory agencies also may approve a product candidate for fewer or more limited indications or patient

populations than requested or may grant approval subject to the conduct of post-marketing studies. In addition,

regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful

commercialization of our product candidates.

The FDA, EMA and other regulatory agencies review the Quality or Chemistry, Manufacturing and Controls, or

CMC, section of regulatory filings. Any aspects found unsatisfactory by regulatory agencies may result in delays

in clinical trials and commercialization. In addition, the regulatory agencies typically conduct pre-approval

inspections at the time of a BLA, MAA or comparable filing. Any findings by regulatory agencies and failure to

comply with requirements may lead to delay in approval and failure to commercialize the potential mRNA product

candidate.

If we experience delays in obtaining, or if we fail to obtain, approval of any product candidates we may develop,

the commercial prospects for those product candidates will be harmed, and our ability to generate revenues will

be materially impaired. Additionally, even if we are successful in obtaining marketing approval for product

candidates, because our preclinical studies and clinical trials have not been designed with specific

commercialization considerations, the commercial prospects for those product candidates could be harmed, and

our ability to generate revenues could be materially impaired.

We are developing product candidates and services, including our oncology pipeline and ADC product

candidates, in an environment of rapid technological and scientific change, including evolving standards

of care, and geopolitical uncertainties, and our failure to effectively compete would prevent us from

achieving significant market penetration. Most of our competitors have significantly greater resources

than we do and we may not be able to compete successfully.

The pharmaceutical market is intensely competitive and rapidly changing. Many large pharmaceutical and

biotechnology companies, academic institutions, governmental agencies, and other public and private research

organizations are pursuing the development of novel drugs for the same diseases that we are targeting or expect

to target. Many of our competitors have:

–greater financial, technical and human resources than we have at every stage of the discovery, development,

manufacture and commercialization of products;

–more extensive experience in preclinical testing, conducting clinical trials, obtaining regulatory approvals and

manufacturing, marketing and selling drug products;

–product candidates that are based on previously tested or accepted technologies;

–products that have been approved or are in late stages of development; and

–collaborative arrangements in our target markets with leading companies and research institutions.

Annual Report on Form 20-F for the year ended December 31, 2025


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We will continue to face intense competition from products that have already been approved and accepted by

the medical community for the treatment of the conditions for which we may develop products in the future. We

also expect to face competition from new products that enter the market. There are a number of products

currently under development, which may become commercially available in the future, for the treatment of

conditions for which we are trying, or may in the future try, to develop drugs. These drugs may be more effective,

safer, less expensive, or marketed and sold more effectively than any products we develop.

We anticipate competing with the largest pharmaceutical companies in the world, many of which are currently

conducting research in the fields of infectious diseases, immuno-oncology, rare genetic diseases and cancer

immunotherapies. Some of these companies have greater financial and human resources than we currently

have. In addition to these large pharmaceutical companies, we may directly compete with fully-integrated

biopharmaceutical companies and other immunotherapy-focused oncology companies, as well as a number of

companies focused on immunotherapies or shared tumor antigen and neoantigen therapeutics, some of which

have entered into collaboration and funding agreements with larger pharmaceutical or biotechnology companies.

We also face competition from other companies and institutions that continue to invest in innovation in the ADC

field.

If we successfully develop other product candidates, and obtain approval for them, we will face competition

based on many different factors, including:

–the safety and effectiveness of our products relative to alternative therapies, if any;

–the ease with which our products can be administered and the extent to which patients accept relatively new

routes of administration;

–the timing and scope of regulatory approvals for these products;

–the availability and cost of manufacturing and commercialization capabilities;

–the price of any approved immunotherapy;

–reimbursement coverage; and

–intellectual property position.

Following our acquisition of InstaDeep Ltd., or InstaDeep, we also face competition in the rapidly growing and

developing artificial intelligence, or AI, industry. Our competitors may develop or commercialize products and

services with significant advantages over any products we develop based on any of the factors listed above or

on other factors. In addition, our competitors may develop collaborations with or receive funding from larger

pharmaceutical, biotechnology or technology companies, providing them with an advantage over us. Our

competitors therefore may be more successful in commercializing their products and services than we are, which

could adversely affect our competitive position and business. Competitive products and services may make any

products and services we develop obsolete or non-competitive before we can recover the expenses of

developing and commercializing such products, if approved, and services.

Our product candidates may not work as intended, may cause undesirable effects or may have other

properties that could delay or prevent their regulatory approval, limit the commercial profile of an

approved label, or result in significant negative consequences following marketing approval, if any.

As with most medicinal products, use of our product candidates could be associated with undesirable effects or

adverse events which can vary in severity from minor reactions to death and in frequency from infrequent to

prevalent. The potential for adverse events is especially acute in the oncology setting, where patients may have

advanced disease, impaired organ function, compromised immune and other systems and may be receiving

Annual Report on Form 20-F for the year ended December 31, 2025


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numerous other therapies. Undesirable side effects or unacceptable toxicities caused by our product candidates

could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more

restrictive label or the delay or denial of regulatory approval by the FDA, the EMA or comparable regulatory

authorities. Results of our trials could reveal a high and unacceptable severity and prevalence of adverse

reactions that negatively affect the benefit/risk assessment .

If unacceptable side effects arise in the development of our product candidates, we, the FDA, competent

authorities of EU member states, ethics committees, the institutional review boards, or IRBs, at the institutions in

which our studies are conducted, or the Data Safety Monitoring Board, or DSMB, could suspend or terminate our

clinical trials. The FDA or comparable regulatory authorities could also order us to cease clinical trials or deny

approval of our product candidates for any or all targeted indications. Treatment-related side effects could also

affect patient recruitment or the ability of enrolled patients to complete any of our clinical trials or result in product

liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating

medical staff. We are committed to training medical personnel using our product candidates to understand the

side effect profiles for our clinical trials, as well as providing guidance to prescribers upon any commercialization

of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our

product candidates could result in patient injury or death. Any of these occurrences may harm our business,

financial condition and prospects significantly.

Clinical trials are strictly regulated and monitored by sponsors, independent data and safety monitoring

boards, ethics committees, and regulatory agencies. Despite adequate risk minimization measures,

unexpected events may occur that could adversely impact patients’ safety and/or affect our ability to

obtain regulatory approvals and, if approved, commercialize our product candidates.

In our ongoing and planned clinical trials, we have contracted, and are expected to continue to contract, with

academic medical centers and hospitals experienced in the assessment and management of toxicities arising

during clinical trials. Nonetheless, these centers and hospitals may have difficulty observing patients and treating

toxicities, which may be more challenging due to personnel changes, inexperience, shift changes, house staff

coverage or related issues. This could lead to more severe or prolonged toxicities or even patient deaths, which

could result in us or the FDA, the EMA or other comparable regulatory authority delaying, suspending or

terminating one or more of our clinical trials, and which could jeopardize regulatory approval. The centers using

our products, if and when approved, could also have difficulty managing any adverse effects of our products, or

use medicines that do not adequately control such undesirable effects or that have a detrimental impact on the

efficacy of the treatment.

In addition, even if we successfully advance our product candidates into and through clinical trials, such trials will

likely only include a limited number of patients and limited duration of exposure to our product candidates. As a

result, we cannot be assured that adverse effects of our product candidates will not be uncovered when a

significantly larger number of patients are exposed to the product candidate. Further, any clinical trials may not

be sufficient to determine the effects and safety consequences of taking our product candidates over a multi-year

period.

If any of our product candidates receives marketing approval and we or others later identify undesirable effects

caused by such products, a number of potentially significant negative consequences could result, including:

–regulatory authorities may withdraw their approval of the product;

–we may be required to recall a product or change the way such product is administered to patients;

–additional restrictions may be imposed on the marketing of the particular product or the manufacturing

processes for the product or any component thereof;

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–regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a

contraindication;

–we may be required to implement a Risk Evaluation and Mitigation Strategy, or REMS, or create a Medication

Guide outlining the risks of such side effects for distribution to patients;

–we could be sued and held liable for harm caused to patients;

–the product may become less competitive; and

–our reputation may be negatively impacted.

Any of the foregoing events could prevent us from achieving or maintaining market acceptance of the particular

product candidate, if approved, and result in the loss of significant revenues to us, which would materially and

adversely affect our results of operations and business. In addition, if one or more of our product candidates or

our immunotherapy approach generally prove to be unsafe, our technology platforms and pipeline could be

affected, which would have a material and adverse effect on our business, financial condition, results of

operations and prospects.

Preclinical development is uncertain. Our preclinical programs may experience delays or may never

advance to clinical trials, which would adversely affect our ability to obtain regulatory approvals or

commercialize these programs on a timely basis or at all and would have an adverse effect on our

business.

Much of our pipeline is in preclinical development and these programs could be delayed or not advance into the

clinic. Before we can initiate clinical trials for product candidates, we must complete extensive preclinical studies,

including IND-enabling Good Laboratory Practice toxicology testing, that support our planned Investigational

New Drug applications, or INDs, in the United States or similar applications in other jurisdictions. We must also

complete extensive work on CMC activities (including collecting yield, purity and stability data) to be included in

the IND filing. CMC activities for a new category of medicines such as mRNA therapies require extensive

manufacturing processes and analytical development, which are uncertain and lengthy. For instance, batch

failures have occurred as we scale up our manufacturing and may occur in the future. In addition, we have had

in the past, and may in the future have, difficulty identifying appropriate buffers and storage conditions to enable

sufficient shelf life of batches of our preclinical or clinical product candidates. If we are required to produce new

batches of our product candidates due to insufficient shelf life, it may delay the commencement or completion of

preclinical or clinical trials of such product candidates. For example, we cannot be certain of the timely

completion or outcome of our preclinical testing and studies and cannot predict if the FDA or other regulatory

authorities will accept the results of our preclinical testing or our proposed clinical programs or if the outcome of

our preclinical testing, studies and CMC activities will ultimately support the further development of our

programs. As a result, we cannot be sure that we will be able to submit INDs or similar applications for our

preclinical programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or

similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.

Clinical development involves a lengthy and expensive process with an uncertain outcome, and delays

can occur for a variety of reasons outside of our control. Clinical trials of our product candidates may be

delayed, certain programs may never advance in the clinic or may be more costly to conduct than we

anticipate, and we may have difficulty recruiting patients to participate in clinical trials, any of which can

affect our ability to fund our company and would have a material adverse impact on our business.

Clinical testing is expensive and complex and can take many years to complete. Its outcome is inherently

uncertain. We may not be able to initiate, may experience delays in, or may have to discontinue clinical trials for

our product candidates. We and our collaborators also may experience numerous unforeseen events during, or

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as a result of, any clinical trials that we or our collaborators conduct that could delay or prevent us or our

collaborators from successfully developing our product candidates, including:

–the FDA, other regulators, 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 for any number of reasons, including concerns

regarding safety and aspects of the clinical trial design;

–we may experience delays in reaching, or fail to reach, agreement on favorable terms with prospective trial

sites and prospective CROs, the terms of which can be subject to extensive negotiation and may vary

significantly among different CROs and trial sites;

–we have optimized in the past and may in the future optimize our manufacturing processes, including through

changes to the scale and site of manufacturing, which may lead to additional studies (including bridging and

bioequivalence studies) or potentially significant changes in our clinical trial designs, requiring additional cost

and time, and, as a consequence, lead to a delay in plans for progressing one or more product candidates;

–the outcome of our preclinical studies and our 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;

–we may be unable to establish clinical endpoints that applicable regulatory authorities would consider clinically

meaningful;

–in an effort to optimize product features, we have made in the past and may continue to make changes to our

product candidates after we commence clinical trials of a medicine which may require us to repeat earlier

stages of clinical testing or delay later-stage testing of the medicine;

–clinical trials of any product candidates may fail to show safety or efficacy, or may produce negative or

inconclusive results, and we may decide, or regulators may require us, to conduct additional nonclinical

studies or clinical trials, or we may decide to abandon product development programs;

–differences in trial design between early-stage clinical trials and later-stage clinical trials may make it difficult

to extrapolate the results of earlier clinical trials to later clinical trials;

–preclinical and clinical data are often susceptible to varying interpretations and analyses, and many product

candidates believed to have performed satisfactorily in preclinical studies and clinical trials have nonetheless

failed to obtain marketing approval;

–our product candidates may have undesirable effects or other unexpected characteristics. One or more of

such effects or events could cause regulators to impose a clinical hold on the applicable trial, or cause us or

our investigators, IRBs or ethics committees to suspend or terminate the trial of that product candidate or any

other of our product candidates for which a clinical trial may be ongoing;

–the number of trial participants required for clinical trials of any product candidates may be larger than we

anticipate, identification of trial participants for such trials may be limited, enrollment in these clinical trials may

be slower than we anticipate due to perceived adverse effects, limited patient populations, competitive trials,

or other reasons, or participants may withdraw from clinical trials or fail to return for post-treatment follow-up at

a higher rate than we anticipate;

–despite robust sponsor oversight, our and our collaborators’ third-party contractors may fail to comply with

regulatory requirements or meet their contractual obligations in a timely manner, or at all, or may deviate from

the clinical trial protocol or withdraw from the trial, which may require the addition of new clinical trial sites;

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–regulators may elect to impose a clinical hold, or we, our investigators, IRBs or ethics committees may elect to

suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory

requirements or a finding that the participants are being exposed to an unacceptable benefit-risk ratio;

–with respect to infectious disease vaccine trials in particular, we have to wait for a particular level of infection in

the placebo arm in order to assess protection provided by vaccine, and we cannot control the rate of exposure

or infection which can make timing uncertain;

–patient characteristics, the rate of disease progression, and other external influences beyond our control can

make the timing of analysis uncertain, particularly in the case of later-stage oncology trials;

–the cost of preclinical or nonclinical testing and studies and clinical trials of any product candidates may be

greater than we anticipate;

–the supply or quality of our product candidates or other materials necessary to conduct clinical trials may be

insufficient or inadequate;

–safety or efficacy concerns regarding our product candidates may result from any concerns arising from

nonclinical or clinical testing of other therapies targeting a similar disease state or other therapies, such as

gene therapy, that are perceived as similar to ours; and

–the FDA or other regulatory authorities may require us to submit additional data, such as long-term toxicology

studies, or impose other requirements before permitting us to initiate a clinical trial.

We could also encounter delays if a clinical trial is suspended or placed on hold by us, the FDA, or other

regulatory authorities, ethics committees, or the IRBs of the institutions in which such trials are being conducted,

or if such trial is recommended for suspension or termination by the DSMB. In the event a trial is suspended or

placed on hold, it may, upon further analysis, be terminated altogether. If a pivotal trial is terminated, the relevant

program may also be subject to delays or termination. We may in the future be delayed in gaining clearance

from the FDA or other regulators to initiate clinical trials through, among other things, the imposition of a clinical

hold in order to address comments from such regulators on our clinical trial design or other elements of our

clinical trials. A suspension or termination may be imposed 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 resulting in the imposition of a

clinical hold; unforeseen safety issues or adverse side effects; failure to demonstrate a benefit, or adequate

benefit-risk ratio, from using a product candidate; failure to establish or achieve clinically meaningful trial

endpoints; changes in governmental regulations or administrative actions; or lack of adequate funding to

continue the clinical trial. 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 product candidates. We could

also experience delays if physicians encounter unresolved ethical issues associated with enrolling patients in

clinical trials of our product candidates in lieu of prescribing existing treatments that have established safety and

efficacy profiles.

We expect the novel nature of our product candidates to create further challenges in obtaining regulatory

approval. For example, the FDA and regulatory authorities in other jurisdictions have limited experience with

commercial development of several of our technologies. The FDA may require an Advisory Committee to

deliberate on the adequacy of the safety and efficacy data to support licensure. The opinion of the Advisory

Committee, although not binding, may have a significant impact on our ability to obtain licensure of the product

candidates based on the completed clinical trials, as the FDA often adheres to the Advisory Committee’s

recommendations. Accordingly, the regulatory approval pathway for our product candidates may be uncertain,

complex, expensive and lengthy, and approval may not be certain.

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We must also complete extensive work on CMC activities that require extensive manufacturing processes and

analytical development, which are uncertain and lengthy. The FDA and other regulatory authorities have

indicated that, prior to commencing later stage clinical trials for our mRNA-based product candidates, we will

need to scale up and further refine assays to measure and predict the potency of a given dose of these product

candidates. Any delay in the scaling and refining of assays that are acceptable to the FDA or other regulatory

authorities could delay the start of future clinical trials. Further, the FDA or other regulatory authorities may

disagree with our clinical trial design and our interpretation of data for our clinical trials or may change the

requirements for approval even after they have reviewed and commented on the design for our clinical trials.

Significant additional preclinical or nonclinical testing and studies or clinical trial delays for our product

candidates also could allow our competitors to bring products to market before we do, potentially impairing our

ability to successfully commercialize our product candidates and harming our business and results of operations.

Any delays in the development, or the suspension of development, of our product candidates may harm our

business, financial condition and prospects significantly.

In addition, on June 28, 2024, the Supreme Court overturned the Chevron doctrine in the combined cases of

Loper Bright Enterprises v. Raimondo and Relentless Inc. v. Department of Commerce. The Chevron doctrine

gave deference to regulatory agencies in litigation against the FDA and other agencies. In addition, the Supreme

Court decided Corner Post, Inc. v. Board of Governors of the Federal Reserve System, which lengthened the

time in which some challenges to agency rules can be initiated. As a result of these cases, more plaintiffs may

bring lawsuits against the FDA to challenge longstanding decisions and policies of the FDA, which could

undermine the FDA’s authority, lead to uncertainties in the industry, and disrupt the FDA’s normal operations,

which could delay the FDA’s review of our marketing applications.

If we or our collaborators encounter difficulties enrolling participants in our clinical trials, our clinical

development activities could be delayed or otherwise adversely affected.

We depend on enrollment of participants in our clinical trials for our product candidates. In the past, our

collaborators have found, and we or our collaborators may in the future find, it difficult to enroll trial participants in

our clinical studies, which could delay or prevent clinical studies of our product candidates. Identifying and

qualifying trial participants to participate in clinical studies of our product candidates is critical to our success.

The timing of our clinical studies depends on the speed at which we can recruit trial participants to participate in

testing our product candidates. Delays in enrollment may result in increased costs or may affect the timing or

outcome of the planned clinical trials, which could prevent completion of these trials and adversely affect our

ability to advance the development of our product candidates. If trial participants are unwilling to participate in

our studies because of negative publicity from adverse events in our trials or other trials of similar products, or

those related to a specific therapeutic area, or for other reasons, including competitive clinical studies for similar

patient populations, the timeline for recruiting trial participants, conducting studies, and obtaining regulatory

approval of potential products may be delayed. These delays could result in increased costs, delays in

advancing our product development, delays in testing the effectiveness of our product, or termination of the

clinical studies altogether.

We may not be able to identify, recruit and enroll a sufficient number of trial participants, or those with required or

desired characteristics to achieve diversity in a study, to complete our clinical trials in a timely manner. Patient

and subject enrollment is affected by factors including:

–severity of the disease under investigation;

–complexity and design of the study protocol;

–size of the patient population;

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–eligibility criteria for the study in question;

–proximity and availability of clinical study sites for prospective trial participants;

–availability of competing therapies and clinical trials, including between our own clinical trials;

–efforts to facilitate timely enrollment in clinical trials;

–patient referral practices of physicians;

–ability to monitor trial participants adequately during and after treatment;

–ability to recruit clinical trial investigators with the appropriate competencies and experience;

–clinicians’ and trial participants’ perceptions of the potential advantages and side effects of the product

candidate being studied in relation to other available therapies, including any new drugs or treatments that

may be approved for the indications we are investigating;

–our ability to obtain and maintain participant informed consent;

–major changes in the approval status of competitor investigational products during the clinical trial period; and

–the risk that trial participants enrolled in clinical trials will not complete a clinical trial.

In addition, our clinical trials may compete with other clinical trials for product candidates that are in the same

therapeutic areas as our product candidates, and this competition will reduce the number and types of trial

participants available to us because some trial participants who might have opted to enroll in our trials may

instead opt to enroll in a trial being conducted by a third party. Since the number of qualified clinical investigators

is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our

competitors use, which will reduce the number of trial participants who are available for our clinical trials at such

clinical trial sites. Moreover, because in some cases our product candidates represent a therapeutic novelty in

contrast to more traditional methods for disease treatment and prevention, potential trial participants and their

doctors may be inclined to use conventional therapies or other investigational therapies rather than enroll trial

participants in any future clinical trial involving more novel product candidates. Additionally, if new product

candidates, such as gene editing therapies, show encouraging results, potential trial participants and their

doctors may be inclined to enroll trial participants in clinical trials using those product candidates. If such new

product candidates show discouraging results or other adverse safety indications, potential trial participants and

their doctors may be less inclined to enroll trial participants in our clinical trials.

In particular, certain conditions for which we plan to evaluate our current product candidates are rare diseases

with limited patient pools from which to draw for clinical trials. The eligibility criteria of our clinical trials will further

limit the pool of available trial participants. Additionally, the process of finding and diagnosing patients may prove

costly.

We, our collaborators, and other third parties on whom we rely conduct various activities, including

research, clinical trials, manufacturing and, where approved, marketing, in jurisdictions across the

globe. Such activities are subject to a variety of risks which could materially and adversely affect our

business.

Our activities increasingly span different jurisdictions. For example, clinical trials of our product candidates are

currently being conducted in several countries, and we plan to commercialize our product candidates, if

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approved, globally. Accordingly, we are subject to additional risks related to operating in multiple countries,

including:

–differing regulatory requirements in such countries;

–differences in the standard of care across jurisdictions, which complicates the choice of adequate comparator

therapies in global trials;

–unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements;

–increased difficulties in managing the logistics and transportation of storing and shipping product candidates

produced in Germany and shipping the product candidate to the patient abroad;

–import and export requirements and restrictions;

–restrictions on transfers of information, including certain technologies and personal data;

–economic weakness, including inflation, or changes to the political climate, public sentiment, and government

policy preferences in certain economies and markets;

–compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

–taxes, including withholding of payroll taxes;

–currency fluctuations, which could result in increased operating expenses and reduced revenue, and other

obligations incident to doing business in another country;

–difficulties staffing and managing operations outside of Germany;

–workforce uncertainty in countries where labor unrest is more common;

–differing payor reimbursement regimes, governmental payors or patient self-pay systems, and price controls;

–potential liability under the U.S. Foreign Corrupt Practices Act of 1977 or comparable regulations in other

jurisdictions;

–challenges enforcing our contractual and intellectual property rights, especially in those countries that do not

respect and protect intellectual property rights to the same extent as Germany and the United States;

–production shortages resulting from any events affecting raw material supply or manufacturing capabilities

abroad; and

–business interruptions resulting from geopolitical actions, including war and terrorism, or public health

epidemics or pandemics.

As part of our global operations, we and our collaborators rely on relationships with entities based in various

jurisdictions, including for clinical research and manufacturing activities and other regional operational needs.

Such relationships may involve the use of our or others’ intellectual property. We expect to continue to rely on

such entities, which include locally-based contract manufacturing organizations, or CMOs, and CROs, in the

future. For example, we and our collaborators rely on WuXi Biologics Co., Ltd. and its affiliates for outsourcing

activities related to manufacturing and the supply chain, research and development, certain IP, and

commercialization readiness for certain of our product candidates. Such entities are subject to evolving local

regulatory requirements, and may also be subject to U.S. and EU legislation, including the recently enacted U.S.

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BIOSECURE Act, sanctions, trade restrictions, and/or other regulations. Such requirements could increase the

cost or reduce the supply of material available to us, delay or restrict the procurement or supply of such material,

or have an adverse affect on our ability to secure significant commitments from governments to purchase our

potential therapies.

Further, governments may turn, and have turned, to trade barriers to protect their domestic industries against

foreign imports, thereby increasing our cost to operate globally. If significant tariffs or other restrictions are

imposed on imports by the United States and related countermeasures are taken by impacted countries, our

business, including operating results, cash flows, and financial condition, may be adversely affected. Recently,

trade and tariff policies among the United States and other countries have been unsettled and are subject to

frequent changes. The U.S. government has imposed tariffs and other trade restrictions on goods across a range

of industries, and such actions have at times prompted retaliatory measures by affected countries such as

China, Canada and the European Union. While tariffs with certain countries have been temporarily reduced or

paused, the imposition of new tariffs will likely be met with further reciprocal tariffs, thus increasing the possibility

of a global trade war. If further tariffs are imposed on a broader range of imports, or if retaliatory trade measures

are enacted by affected countries, these factors could significantly increase the cost to our global clinical

research and manufacturing activities, adversely affect the commercial sale of our COVID-19 vaccines, and

harm our competitive position in key markets. Additionally, ongoing trade tensions and uncertainty regarding

future trade policies could negatively impact global economic conditions and consumer confidence, further

affecting our global operations.

As noted above, we and our partners have conducted and are expecting in the future to conduct clinical trials for

our product candidates at clinical sites located outside of the United States. Although the FDA may accept data

from clinical trials outside the United States that are not conducted under an IND, acceptance of this data in

support of a marketing application or IND requires the clinical trial to have been conducted in accordance with

GCPs, and that the FDA is able to validate the data from the clinical trial through an onsite inspection if it deems

such inspection necessary. Where data from non-U.S. clinical trials are intended to serve as the sole basis for

marketing approval in the United States, the FDA will not approve the application on the basis of non-U.S. data

alone unless those data are considered applicable to the U.S. patient population and U.S. medical practice, the

clinical trials were performed by clinical investigators of recognized competence, and the data is considered valid

without the need for an onsite 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 onsite inspection or other appropriate means. There can be no

assurance the FDA will accept data from clinical trials conducted outside of the United States in support of a

marketing application. If the FDA does not accept data from our clinical trials of our product candidates, it would

likely result in the need for additional clinical trials, which would be costly and time-consuming and delay or

permanently halt our development of a product candidate.

These and other risks associated with our international operations and our collaborations with our collaborators

may materially adversely affect our ability to attain or maintain profitable operations.

Interim top-line and preliminary data from studies or trials that we announce or publish from time to time

may change as more 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 preclinical studies or clinical trials.

Interim data are subject to the risk that one or more of the outcomes may materially change as more data

become available. We also make assumptions, estimations, calculations and conclusions as part of our analyses

of data, and we may not have received or had the opportunity to fully evaluate all data. As a result, the top-line

results that we report may differ from future results of the same studies, or different conclusions or

considerations may qualify such results, once additional data have been received and fully evaluated.

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 and

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preliminary data should be viewed with caution until the final data are available. Additionally, interim data from

clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may

materially change as patient enrollment continues and more patient data become available. Adverse differences

between preliminary or interim data and final data could significantly harm our business prospects.

Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates,

calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could

impact the value of the particular program, the approvability or commercialization of the particular product

candidate or product and our company in general. In addition, the information we choose to disclose publicly

regarding a particular study or clinical trial is based on what is typically extensive information, and our

securityholders may not agree with what we determine is the material or otherwise appropriate information to

include in our disclosure. Any information we determine not to disclose may ultimately be deemed significant by

our securityholders or others with respect to future decisions, conclusions, views, activities or otherwise

regarding a particular product candidate or our business. If the top-line data that we report differ from actual

results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain

approval for, and commercialize, product candidates may be harmed, which could significantly harm our

business prospects.

Results of earlier studies and trials of our product candidates may not be predictive of future trial

results.

Success in preclinical studies and early clinical trials does not ensure that later clinical trials will be successful. A

number of companies in the biotechnology and pharmaceutical industries have suffered significant setbacks in

clinical trials, even after positive results in earlier preclinical studies or clinical trials. These setbacks have been

caused by, among other things, preclinical findings made while clinical trials were underway and safety or

efficacy observations made in clinical trials, including previously unreported adverse events. Notwithstanding any

potential promising results in earlier studies and trials, we cannot be certain that we will not face similar

setbacks. Even if our clinical trials are completed, the results may not be sufficient to obtain regulatory approval

for our product candidates. In addition, the results of our preclinical studies may not be predictive of the results of

outcomes in human clinical trials. For example, our tumor-specific cancer immunotherapy candidates and any

future product candidates may demonstrate different chemical, biological and pharmacological properties in

patients than they do in laboratory studies or may interact with human biological systems in unforeseen or

harmful ways. Product candidates in later stages of clinical trials may fail to show the desired pharmacological

properties or safety and efficacy traits despite having progressed through preclinical studies and initial clinical

trials. Even if we are able to initiate and complete clinical trials, the results may not be sufficient to obtain

regulatory approval for our product candidates.

Our planned clinical trials or those of our collaborators may be less efficacious or may reveal significant

adverse events not seen in our preclinical or nonclinical studies and may result in a safety profile that

could delay or terminate clinical trials, or delay or prevent regulatory approval or market acceptance of

any of our product candidates.

There is typically an extremely high rate of attrition for product candidates across categories of medicines

proceeding through clinical trials.

These product candidates may fail to show the desired safety and efficacy profile in later stages of clinical trials

despite having progressed through nonclinical studies and initial clinical trials. A number of companies in the

biopharmaceutical industry have suffered significant setbacks in later-stage clinical trials due to lack of efficacy

or unacceptable safety profiles, notwithstanding promising results in earlier trials. Most product 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 product

candidates.

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Many of our product candidates are being developed or are intended to be co-administered with other

developmental therapies or approved medicines. For example, autogene cevumeran (BNT122/RO7198457) is

being developed to be co-administered with checkpoint inhibitors. Such combinations may have additional side

effects, which may be difficult to predict in future clinical trials.

If significant adverse events or other side effects are observed in any of our current or future clinical trials, we

may have difficulty recruiting trial participants to any of our clinical trials, trial participants may withdraw from

trials, or we may be required to abandon the trials or our development efforts of one or more product candidates

altogether. We, the FDA or other regulatory authorities, ethics committees or an IRB may impose a clinical hold

on, or suspend or terminate, clinical trials of a product candidate at any time for various reasons, including a

belief that participants 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 drug from obtaining or maintaining marketing approval, an unfavorable

benefit-risk ratio 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.

If we are not successful in discovering, developing and commercializing additional product candidates

beyond our current portfolio, our ability to expand our business and achieve our strategic objectives

would be impaired.

Although a substantial amount of our efforts focus on the clinical trials and potential approval of our existing

product candidates, a key element of our strategy is to discover, develop and potentially commercialize

additional products beyond our current portfolio to treat various conditions and in a variety of therapeutic areas.

We intend to do so by investing in our own drug and target discovery efforts, exploring potential collaborations

for the development of new products, and in-licensing technologies. Identifying new product candidates requires

substantial technical, financial and human resources, whether or not any product candidates are ultimately

identified. Even if we identify product candidates that initially show promise, we may fail to develop and

commercialize such products successfully for many reasons, including the following:

–the research methodology used may not be successful in identifying potential product candidates;

–competitors may develop alternatives that render our product candidates obsolete;

–product candidates we develop may nevertheless be covered by third parties’ patents or other exclusive

rights;

–a product candidate may, on further study, be shown to have harmful side effects or other characteristics that

indicate it is unlikely to be effective or otherwise does not meet applicable regulatory criteria;

–we may discontinue the development of a product candidate;

–a product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or

at all; and

–an approved product may not be accepted as safe and effective by trial participants, the medical community or

third-party payors.

If we are unsuccessful in identifying and developing additional products, our potential for growth may be

impaired.

mRNA drug development carries substantial clinical development and regulatory risks due to limited

regulatory experience with mRNA immunotherapies.

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To our knowledge, other than our, Moderna, Inc.’s and Arcturus Therapeutics’ vaccines, no mRNA

immunotherapies have been approved or received emergency use authorization or conditional marketing

authorization to date by the FDA or the EMA. Successful discovery and development of mRNA-based (and

other) immunotherapies by either us or our collaborators is highly uncertain and depends on numerous factors,

many of which are beyond our or their control. Our product candidates that appear promising in the early phases

of development may fail to advance, experience delays in the clinic or clinical holds, or fail to reach the market

for many reasons, including:

–discovery efforts aimed at identifying potential immunotherapies may not be successful;

–nonclinical or preclinical study results may show product candidates to be less effective than desired or have

harmful or problematic side effects;

–clinical trial results may show the product candidates to be less effective than expected, including a failure to

meet one or more endpoints or have unacceptable side effects or toxicities;

–manufacturing or distribution failures or insufficient supply of GMP materials for clinical trials or higher than

expected cost could delay or set back clinical trials, or make our product candidates commercially

unattractive;

–our improvements in the manufacturing processes may not be sufficient to satisfy the clinical or commercial

demand of our product candidates or regulatory requirements for clinical trials;

–changes that we make to optimize our manufacturing, testing or formulating of GMP materials could impact

the safety, tolerability and efficacy of our product candidates;

–pricing or reimbursement issues or other factors could delay clinical trials or make any immunotherapy

uneconomical or noncompetitive with other therapies;

–changing social and political preferences regarding vaccines and mRNA therapies;

–the failure to timely advance our programs or receive the necessary regulatory approvals, or a delay in

receiving such approvals, due to, among other reasons, slow or failure to complete enrollment in clinical trials,

withdrawal by trial participants from trials, failure to achieve trial endpoints, additional time requirements for

data analysis, data integrity issues, BLA, MAA or the equivalent application, discussions with the FDA or the

EMA, a regulatory request for additional nonclinical or clinical data, or safety formulation or manufacturing

issues may lead to our inability to obtain sufficient funding; and

–the proprietary rights, products and technologies of our competitors may prevent our immunotherapies from

being commercialized.

For administrative purposes, some mRNA products may be classified together with gene therapy products by the

FDA or other regulatory agencies. Unlike certain gene therapies that irreversibly alter cell DNA and may be

subsequently subject to specific safety concerns, mRNA products are not designed to localize to the cell nucleus

or interact with the genome. Side effects observed in other gene therapies, however, could negatively impact the

perception of immunotherapies despite the differences in mechanism. In addition, unclear or inconsistent

regulatory classification of mRNA products may result in uncertainties regarding the regulatory requirements and

pathways for marketing approval. On the other hand, mRNA-based vaccines for the prevention of infectious

diseases, like our COVID-19 vaccine, are not currently classified as gene therapies in most regions. The

regulatory pathway for an individualized therapy, such as our Individualized Neoantigen Specific Immunotherapy,

or iNeST, an mRNA-based immunotherapy where each patient receives a different combination of mRNAs,

remains undetermined. The number and design of the clinical and preclinical studies required for the approval of

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these types of medicines have not been established, may be different from those required for advanced

medicinal therapy products or therapies that are not individualized or may require safety testing like gene

therapy products. Moreover, the length of time necessary to complete clinical trials and submit an application for

marketing approval by a regulatory authority varies significantly from one pharmaceutical product to the next and

may be difficult to predict.

Our future success depends on our ability to retain key employees, consultants and advisors and to

attract, retain and motivate qualified senior management and scientific personnel.

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 are highly

dependent upon members of our management and scientific teams. We may not be able to retain these persons

due to the competitive environment in the biotechnology industry, as well as a current global shortage of these

highly qualified individuals. The loss of any of these persons’ services may adversely impact the achievement of

our research, development, financing and commercialization objectives. We are also aware of physical threats

made against certain of these people. In response to these threats, we have deployed personal protection for

such individuals and increased our security generally. We currently do not have “key person” insurance on any of

our employees.

In addition, we rely on consultants, contractors and advisors, including scientific and clinical advisors, to assist

us in formulating our research and development, regulatory approval and commercialization strategy. Our

consultants and advisors may be employed by employers other than us and may have commitments under

consulting or advisory contracts with other entities that may limit their availability to us. The loss of the services

of one or more of our current employees or advisors might impede the achievement of our research,

development, regulatory approval and commercialization objectives. In addition, we have flexibly grown our

workforce through the use of contractors and part-time workers. We may not be able to retain the services of

such personnel, which might result in delays in the operation of our business.

Recruiting and retaining other qualified employees, consultants and advisors for our business, including scientific

and technical personnel, will be critical to our success as well. Competition for skilled personnel, including in

mRNA research, clinical development, clinical operations, regulatory affairs, therapeutic area management,

manufacturing, and AI, is intense and the turnover rate can be high. We may not be able to attract and retain

personnel on favorable terms given the competition among numerous pharmaceutical and biotechnology

companies and academic institutions for individuals with similar skill sets. In addition, adverse publicity, and the

failure to succeed in preclinical studies or clinical trials or in applications for marketing approval may make it

more challenging to recruit and retain qualified personnel. The inability to recruit or loss of services of certain

executives, key employees, consultants or advisors may impede the progress of our research, development and

commercialization objectives and have a material adverse impact on our business, financial condition, results of

operations and prospects.

Our employees, principal investigators and consultants may engage in misconduct or other improper

activities, including non-compliance with regulatory standards and requirements and insider trading,

which could have an adverse effect on the results of our operations.

We are exposed to the risk of fraud or other misconduct by our employees, principal investigators and

consultants, despite our robust efforts to prevent such misconduct through sponsor oversight. Misconduct by

these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the

European Union and other jurisdictions, to provide accurate information to the FDA, the EMA and other

regulatory authorities, to comply with healthcare fraud and abuse laws and regulations in the United States and

abroad, to report financial information or data accurately or to disclose unauthorized activities to us. Such

misconduct also could involve the improper use of information obtained in the course of clinical trials or

interactions with the FDA or other regulatory authorities, which could result in regulatory sanctions and cause

serious harm to our reputation. We have adopted a code of conduct applicable to all of our employees, but it is

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not always possible to identify and deter employee misconduct, 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 government investigations or other actions or lawsuits stemming from a failure to comply with laws or

regulations. 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, financial condition, results of

operations and prospects, including the imposition of significant fines or other sanctions.

Employment-related disputes, including employee litigation and unfavorable publicity, could negatively

affect our future business.

From time to time we may be subject to claims by our employees or regulatory authorities with respect to

employment and workplace matters, including lawsuits or proceedings against us regarding injury, creating a

hostile workplace, discrimination, wage and hour disputes, sexual harassment or other employment issues. In

recent years, there has been an increase in the number of discrimination and harassment claims generally.

Coupled with the expansion of social media platforms and similar devices that allow individuals access to a

broad audience, these claims have had a significant negative impact on some businesses. Certain companies

that have faced employment- or harassment- related lawsuits have had to terminate management or other key

personnel, and have suffered reputational harm that has negatively impacted their business. If we were to face

any employment-related claims, our business could be negatively affected.

The illegal distribution and sale by third parties of counterfeit versions of our COVID-19 vaccine, or, if

approved, our other product candidates, could have a negative impact on our financial performance or

reputation.

Third parties have in the past and may continue to illegally distribute and sell counterfeit versions of COVID-19

vaccines. Counterfeit products are frequently unsafe or ineffective, and may even be life-threatening. Counterfeit

medicines may contain harmful substances or the wrong dosage. However, to distributors and users, counterfeit

products may be visually indistinguishable from the authentic version.

Reports of adverse reactions to counterfeit products, increased levels of counterfeiting, or unsafe vaccines could

materially affect public confidence in our COVID-19 vaccine or other product candidates. It is possible that

adverse events caused by unsafe counterfeit vaccines will mistakenly be attributed to our COVID-19 vaccine, or,

if approved, our other product candidates. In addition, thefts of inventory at warehouses, plants or while in-

transit, which are subsequently improperly stored and which are sold through unauthorized channels, could

adversely impact patient safety, our reputation, and our business. Public loss of confidence in the integrity of our

COVID-19 vaccine or, if approved, our other product candidates, as a result of counterfeiting or theft could have

a material adverse effect on our business, results of operations, and financial condition.

We and our collaborators or other contractors or consultants depend on information technology

systems, and any failure of these systems could harm our business. Security breaches, loss of data and

other disruptions could compromise sensitive information related to our business or prevent us from

accessing critical information and expose us to liability, which could adversely affect our business,

results of operations and financial condition.

Our internal computer systems and those of our current and any future collaborators, vendors, and other

contractors or consultants are vulnerable to damage from computer viruses, unauthorized access, natural

disasters, terrorism, cybersecurity threats, war, and telecommunication and electrical failures. If any such

material system failure, accident or security breach were to occur and cause interruptions in our operations, it

could result in a material disruption of our development programs and our business operations, whether due to a

loss of our trade secrets or other proprietary information or other similar disruptions. For example, the loss of

clinical trial data from one or more ongoing or completed or future clinical trials could result in delays in our

regulatory approval efforts and significantly increase our costs to recover or reproduce the data. In addition,

because of our approach of running multiple clinical trials in parallel, any breach of our computer systems may

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result in a loss of data or compromised data integrity across many of our programs in many stages of

development. Any such breach, loss or compromise of clinical trial participant personal data may also subject us

to civil fines and penalties, including under the EU General Data Protection Regulation, or the GDPR, relevant

law of an EU member state, HIPAA, and other relevant state and federal privacy laws in the United States or in

other jurisdictions. To the extent that any disruption or security breach were to result in a loss of, or damage to,

data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability,

our competitive position could be harmed, and the further development and commercialization of our product

candidates could be delayed.

While we have not experienced any material system failures, accidents or security breaches to date, in

December 2020, we were informed by the EMA that the agency was subject to a cyberattack and that some

documents relating to our regulatory submission for our COVID-19 vaccine candidate, which was stored on an

EMA server, had been unlawfully accessed. None of our systems were breached in connection with this incident

and we are unaware that any study participants were identified through the data being accessed.

We have put systems and procedures in place to minimize the likelihood of such incidents reoccurring; however,

we cannot guarantee that third parties will not be able to gain unauthorized access to or otherwise breach our

systems in the future. Any such unauthorized access or breach could adversely affect our business, results of

operations and financial condition.

Product liability lawsuits against us could cause us to incur substantial liabilities and could limit

commercialization of our current or future product candidates.

We face an inherent risk of product liability exposure related to the testing of any of our current or future product

candidates in clinical trials, and an even greater risk related to any commercialized products, such as our

COVID-19 vaccine. We have received product liability claims against our COVID-19 vaccine, and expect to

receive additional product liability claims in the future. If we cannot successfully defend ourselves against claims

that our products and/or our product candidates have caused injuries, we could incur substantial liabilities.

Regardless of merit or eventual outcome, liability claims may result in:

–decreased demand for any product or product candidate that we may develop;

–loss of revenue;

–substantial monetary awards to patients, healthy volunteers or their children;

–significant time and costs to defend the related litigation;

–withdrawal of clinical trial participants;

–the inability to commercialize any products or product candidates that we may develop; and

–injury to our reputation and significant negative media attention.

We carry clinical trial insurance and product liability insurance, which we believe to be sufficient in light of our

current clinical programs and commercial operations. However, the amount of coverage we have obtained may

not be adequate, and we may seek to further increase insurance coverage limits as our pipeline moves towards

commercialization. As we evolve, 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. On occasion, large judgments have been awarded

in class action lawsuits based on drugs or medical treatments that had unanticipated adverse effects. A

successful product liability claim or series of claims brought against us could cause the price of the ADSs to

decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and

business.

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If our products become subject to a product recall it could harm our reputation, business and financial

results.

The FDA and similar governmental authorities in other jurisdictions have the authority to require the recall of

certain commercialized products. In the case of the FDA, the authority to require a recall of a biologic product

must be based on an FDA finding that a batch, lot or other quantity of the biologic product presents an imminent

or substantial hazard to the public health. In addition, some governmental bodies outside the United States have

the authority to require the recall of any product or product candidate in the event of material deficiencies or

defects in design or manufacture. Manufacturers may, under their own initiative, recall a product if any material

deficiency in a product is found. A government-mandated or voluntary recall by us could occur as a result of

manufacturing errors, design or labeling defects or other deficiencies and issues.

Recalls of any of our products or, if approved, our product candidates, would divert managerial and financial

resources and have an adverse effect on our financial condition and results of operations. A recall

announcement could harm our reputation with customers and negatively affect our sales, if any.

Issues in the development and use of AI, combined with an uncertain regulatory environment, may result

in reputational harm, liability or other adverse consequences to our business.

We are investing in AI technology systems, including through our acquisition of InstaDeep, and such systems are

complex and rapidly changing. We face significant competition from other companies with respect to our AI and

machine learning services, along with an evolving regulatory landscape. The introduction of AI into the

development and manufacturing of our product candidates, or the provision of services relating to AI

technologies and applications, may result in new or enhanced governmental or regulatory scrutiny, litigation,

intellectual property risks, confidentiality or security risks, ethical concerns or other complications that could harm

our business, reputation or financial condition.

Uncertainty around AI may require additional investment in the development and maintenance of proprietary

datasets and development of appropriate protections and safeguards for handling the use of customer data with

AI technologies, which may be costly and could impact our expenses. In addition, AI may create content that

appears correct but is inaccurate or flawed, and if created by third parties, may be mistakenly attributed to us.

Our customers or others may rely on or use this flawed content to their detriment, which may expose us to brand

or reputational harm, competitive harm or legal liability.

Our ability to effectively monitor and respond to the rapid and ongoing developments and expectations

relating to environmental, social and governance, or ESG, matters, including related social expectations

and concerns, may impose unexpected costs or result in reputational or other harm that could have a

material adverse effect on our business, financial condition, cash flows and results of operations and

could cause the price of ADSs representing our ordinary shares to decline.

There are rapid and ongoing developments and changing, sometimes conflicting, expectations relating to ESG

matters and factors such as the environmental impact of our operations, access to our COVID-19 vaccine,

corporate governance, our product stewardship practices, management of business ethics, human rights due

diligence in our own operations and our supply chain, and workforce development. At the same time, ESG

matters, including climate change, are the subject of increased politicization, particularly in the United States.

These factors may result in increased regulatory, social or other scrutiny on us.

We believe we must address climate risks from our own contribution to climate change (inside-out perspective),

risks to our own operations due to physical effects of climate change as well as transition risks (outside-in

perspective), and interactions between both perspectives. To this end, we have set ourselves near-term

scienced-based emissions reduction targets for our own operations (scope 1, 2) and for our supply chain

(supplier engagement target for scope 3), validated by the Science Based Targets initiative, or SBTi, in early

February 2024.

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Additionally, we are addressing increasingly complex regulatory requirements with respect to human rights risks.

These requirements include German legislation, such as the Act on Corporate Due Diligence Obligations for the

Prevention of Human Rights Violations in Supply Chains (Lieferkettensorgfaltspflichtengesetz – LkSG), potential

legislative planning by the European Union, and local or regional regulations. Regulatory frameworks require us

to identify, prevent, mitigate and ideally end the extent of any potential adverse impacts or violations throughout

our own operations and value chain.

Finally, we are faced with increasing ESG related transparency and reporting obligations. These requirements

arise, for example, from the EU Corporate Sustainability Reporting Directive regulation, the European

Sustainability Reporting Standards, and the respective German implementation law and other possible

obligations.

Should we fail to meet our climate protection targets or if we are unable to adequately recognize and respond to

such developments and governmental, societal, investor and NGO expectations relating to such ESG matters,

we may have to pay substantial fines, forego corporate opportunities, become subject to additional scrutiny, incur

unexpected costs or experience damage to our reputation or our various brands. If any of these events were to

occur, there may be a material adverse effect on our business, financial condition, cash flows and results of

operations, and the price of ADSs representing our ordinary shares may decline.

We have observed that in addition to the importance of their financial performance, companies are increasingly

being judged by their performance on ESG matters. A variety of organizations measure the performance of

companies on such ESG topics, and the results of these assessments are widely publicized. We may fail to

comply with standards or best practices put forth by such organizations or by governmental or regulatory bodies.

There can be no certainty that we will manage such issues successfully, or that we will successfully meet

society’s expectations as to our proper role. Any failure or perceived failure by us in this regard could have a

material adverse effect on our reputation and on our business, the price of ADSs representing our ordinary

shares, financial condition, or results of operations, including the sustainability of our business over time.

Risks Related to our COVID-19 Vaccine and the Commercialization of our Pipeline

Demand for our COVID-19 vaccine, though difficult to predict, is expected to continue to decrease in the

near future. Changing market dynamics, including as a result of government policy and public

sentiment, will impact our revenue, which currently depends heavily on sales of our COVID-19 vaccine,

and result in challenges relating to production of our COVID-19 vaccine.

Prior to the commercialization of our COVID-19 vaccine, we had not sold or marketed any products in our

pipeline. As a result, a majority of our total revenues to date are attributable to sales of our COVID-19 vaccine.

However, we have experienced and we expect to continue to experience increasing reductions in demand for

COVID-19 vaccination generally, including for our vaccine, now that the virus has entered an endemic stage and

as a growing proportion of the population becomes vaccinated. We expect that future revenues from sales of our

COVID-19 vaccine will decrease as demand for vaccination wanes. Such revenues will depend on numerous

factors, including:

–the extent to which a COVID-19 vaccine, including any booster shot, continues to be necessary while

COVID-19 remains an endemic virus;

–competition from other COVID-19 vaccines, including those with different mechanisms of action and different

manufacturing and distribution constraints, on the basis of, among other things, efficacy, cost, convenience of

storage and distribution, breadth of approved use, side-effect profile and durability of immune response;

–our ability to successfully and timely develop effective vaccines targeting new variants and mutations of

COVID-19;

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–the extent to which changes in local, national and state government policy preferences in the United States

and other jurisdictions, including changes in vaccine recommendations, and evolving public sentiment affect

demand for COVID-19 vaccines or mRNA therapeutics and our ability to successfully commercialize our

product candidates, if approved;

–our ability to receive full regulatory approvals where we currently have, or previously have had, emergency

use authorizations or equivalents;

–our ability to expand our geographic customer base;

–our pricing and reimbursement negotiations with governmental authorities, private health insurers and other

third-party payors after our initial sales to national governments, including the transition towards ordinary-

course insurance coverage in the public and private sectors;

–the ability of countries and jurisdictions to store and distribute doses of our COVID-19 vaccine to end users at

cold temperatures;

–the safety profile of our COVID-19 vaccine, including if previously unknown undesirable effects or increased

incidence or severity of known undesirable effects are identified with our COVID-19 vaccine;

–intellectual property litigation involving our COVID-19 vaccine and COVID-19 vaccines in general; and

–our manufacturing and distribution capabilities for our COVID-19 vaccine.

We cannot accurately predict the revenues our COVID-19 vaccine will generate in future periods or for how long

our COVID-19 vaccine will continue to generate material revenues, and we cannot ensure it will maintain its

competitive position. Uncertainty in the demand for our COVID-19 vaccine and difficulties in targeting appropriate

supply of our COVID-19 vaccines have in the past resulted, and may in the future result, in significant inventory

write-downs and cancellations of contract manufacturing orders. Our business and financial condition could be

materially affected by lowered COVID-19 vaccine revenues resulting from any of the above factors, or by

production and supply chain difficulties. In addition, if our revenues or market share of, or other financial metrics

relating to, our COVID-19 vaccine do not meet the expectations of investors or securities analysts, the market

price of the ADSs representing our ordinary shares may decline.

Our reported revenue is based in part on preliminary estimates of COVID-19 vaccine sales and costs

from Pfizer that are likely to change in future periods, which may impact our reported financial results.

Our reported revenue is based in part on preliminary estimates from Pfizer and other assumptions and

judgments that we have made, which may be subject to significant uncertainties. Our revenue includes

preliminary estimates in part due to a difference in Pfizer’s financial quarter for subsidiaries outside the United

States, which consequently creates an additional time lag between the recognition of revenues and the receipt of

payment. Although our revenue recognition policy is based on facts and circumstances known to us and various

other assumptions that we believe to be reasonable under the circumstances, our actual results may deviate

from such reported revenue.

We depend on Pfizer to determine and provide estimates of the costs and profits to be shared with us in the

countries where it is commercializing our COVID-19 vaccine under our collaboration agreement with Pfizer for

our COVID-19 vaccine, which we refer to as the Pfizer Agreement. Because the information supplied by Pfizer is

preliminary and subject to change, the revenue we report based on such information is also subject to

finalization. This is particularly true for vaccine sales outside of the United States, where Pfizer has a different

reporting cycle than ours. As a result, we may not have the complete sales and costs results outside of the

United States for months not covered by the reporting period, but we are nonetheless required to report

estimated figures.

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Pfizer has historically provided us with profit figures for our COVID-19 vaccine sales in the United States using

standard U.S. transfer prices and manufacturing and shipping cost variances (as far as those have been

identified) that could be subject to adjustment (e.g., due to changes in manufacturing costs or the price of our

COVID-19 vaccine). Pfizer has also provided estimated profits for COVID-19 vaccine sales outside of the United

States that were preliminary in nature for the last month of a quarter, as Pfizer’s subsidiaries outside of the

United States have a different reporting cycle than ours. These estimated figures have changed, and in the

future such estimated figures are likely to change, as we receive final data from Pfizer for the applicable period in

accordance with the reporting cycle of Pfizer’s ex-U.S. subsidiaries and as actual costs become known. Further,

to the extent that Pfizer does not provide such preliminary information in the future, our provisional sales figures

for territories outside of the United States will be subject to an even greater level of estimate and judgment. Any

changes to the preliminary data we report herein may have an impact on our reported revenues and expenses,

profitability or financial position.

We may be unsuccessful in adapting our COVID-19 vaccine or developing future versions of our

COVID-19 vaccine to protect against variants of the SARS-CoV-2 virus, and even if we are successful, a

market for vaccines against these variants may not develop and our ability to continue to generate

income from sales of our COVID-19 vaccine is uncertain.

The COVID-19 disease itself is unpredictable and each variant comes with varying levels of transmissibility and

severity. Consequently, the burden of the disease may wane or dissipate such that our and other COVID-19

vaccines may be considered less essential from individual and public health perspectives.

Our COVID-19 vaccine was initially developed based upon the genetic sequence of the original SARS-CoV-2

virus that was first detected. The SARS-CoV-2 virus continues to evolve, and new strains of the virus or those

that are already in circulation may prove more transmissible or cause more severe forms of COVID-19 disease

than the predominant strains observed to date. Our vaccine may not be as effective in protecting against existing

and future variant strains of the SARS-CoV-2 virus as it is against the original virus or currently known strains of

the SARS-CoV-2 virus. We and Pfizer intend to continue to observe our COVID-19 vaccine, including variant-

adapted vaccine candidates, in global clinical trials. It is possible that subsequent data from these clinical trials

may not be as favorable as data we submitted to regulatory authorities to support our applications for emergency

use authorization or marketing or conditional marketing approval or that concerns about the safety of our variant-

adapted COVID-19 vaccines will arise from widespread use outside of clinical trials. While we continue to

monitor emerging SARS-CoV-2 strains, undertake investigations into the immunogenicity of our COVID-19

vaccine against new variants as they emerge and develop modified versions of our COVID-19 vaccine against

new variants, these efforts may be unsuccessful, and failure to timely and successfully adapt our vaccine to

variants of the SARS-CoV-2 virus could lead to significant reputational harm and adversely affect our financial

results. Furthermore, variant-adapted COVID-19 vaccines may not receive approval or emergency use

authorization in all jurisdictions, which could adversely affect our business prospects. It is also possible that we

may expend significant resources adapting our COVID-19 vaccine to protect against certain variants of the

SARS-CoV-2 virus, but that a market for adapted vaccines does not develop for one or more variants or that

demand does not align with our projections or cost expenditures. Moreover, even if we are successful in

developing an adapted vaccine and there is a market for the new vaccine, new variants continue to emerge and

any adapted vaccine may not be as effective in protecting against such future variant strains.

If we discover safety issues with our products, including our COVID-19 vaccine, that were not known at

the time of approval, commercialization efforts for our products could be negatively affected, approved

products could lose their approval or sales could be suspended, we could be subject to product liability

claims and our business and reputation could be materially harmed.

Our COVID-19 vaccine and any other product candidates for which we receive approval or emergency use

authorization are subject to continuing regulatory oversight, including the review of additional safety information.

Billions of doses of our COVID-19 vaccine have been delivered worldwide, and our COVID-19 vaccine is being

more widely used by patients as an authorized product than it was used in clinical trials. As a result, undesirable

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effects and other problems may be observed that were not seen or anticipated, or were not as prevalent or

severe, during clinical trials. We cannot provide assurance that newly discovered or developed safety issues will

not arise, and we have received, and expect to continue to receive, product liability claims relating to our

COVID-19 vaccine. With the use of any vaccine by a wide patient population, serious adverse events may occur

from time to time that did not arise in clinical trials or that initially appeared to be unrelated to the vaccine itself

and only with the collection of subsequent information were found to be causally related to the product. Safety

events that arise outside of a clinical trial setting are difficult to monitor, and given the widespread use of our

COVID-19 vaccine, we have experienced difficulty tracking potential treatment-related adverse events on a

global basis. Any safety issues could cause us to suspend or cease marketing of our approved products,

possibly subject us to substantial liabilities, and adversely affect our ability to generate revenue and our financial

condition. The subsequent discovery of previously unknown problems with a product could negatively affect

commercial sales of the product, result in restrictions on the product or lead to the withdrawal of the product from

the market. The reporting of adverse safety events involving our products or public speculation about such

events could cause the price of the ADSs representing our ordinary shares to decline or experience periods of

volatility.

Unexpected safety issues, including any that we have not yet observed in our clinical trials or in real world data,

could lead to significant reputational damage for us and our product development platforms going forward and

other issues, including delays in our other programs, the need for re-design of our clinical trials and the need for

significant additional financial resources.

Failure to comply with continuing regulatory requirements by us or our collaboration partners could

adversely impact regulatory approvals for our products, result in product recalls or suspensions, and/or

subject us to fines and/or other types of liabilities.

If we or our collaborators fail to comply with applicable continuing regulatory requirements, including good

industry practices, such as good manufacturing practices, or GMP, we or our collaborators may be subject to

fines, suspension or withdrawal of regulatory approvals for specific drugs, product recalls and seizures,

operating restrictions and/or criminal prosecutions. We and the manufacturers we engage to make our products

and the manufacturing facilities in which our products are made are subject to periodic review and inspection by

the U.S. Food and Drug Administration, or the FDA, and other regulatory authorities. If problems are identified

during a review or inspection, we or our collaborators may be the subject of adverse regulatory action, including

the issuance of untitled or warning letters, which could result in our inability to use the facility to make our

product or a determination that inventories are not safe for commercial sale. Any of these factors could adversely

affect our business prospects and our financial position could be materially harmed.

The successful commercialization of our product candidates will depend in part on the extent to which

governmental authorities, private health insurers and other third-party payors provide coverage and

adequate reimbursement levels and implement pricing policies favorable to our product candidates.

Failure to obtain or maintain coverage and adequate reimbursement for our product candidates, if

approved, and/or delayed payments from government authorities could limit our ability to market those

products and decrease our ability to generate revenue.

The availability and extent of reimbursement by governmental and private payors is essential for most patients to

be able to afford certain treatments, including our COVID-19 vaccine and other product candidates we may

develop and sell. In addition, because our mRNA product candidates represent an entirely new therapeutic

modality, we cannot accurately estimate how future products we may develop and sell would be priced, whether

reimbursement could be obtained, or any potential revenue. Sales of our product candidates will depend

substantially, both domestically and abroad, on the extent to which the costs of our product candidates will be

paid by healthcare management organizations, or reimbursed by government health administration authorities,

private health coverage insurers and other third-party payors. If reimbursement is not available, or is available

only to limited levels, we may not be able to successfully commercialize our product candidates. Even if

coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or

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maintain pricing sufficient to realize an adequate return on our investment in any of our products. Additionally,

even if pricing terms with governmental authorities are agreed upon, there may be delayed or denied payments.

There is significant uncertainty related to the insurance coverage and reimbursement for newly approved

products in particular in the United States, including genetic medicines. In the United States, the principal

decisions about reimbursement for new medicines are typically made by the Centers for Medicare & Medicaid

Services, or CMS, an agency within the U.S. Department of Health and Human Services, or HHS, as CMS

decides whether and to what extent a new medicine will be covered and reimbursed under Medicare. Private

payors tend to follow CMS to a substantial degree. It is difficult to predict what CMS will decide with respect to

reimbursement for novel products such as ours. Reimbursement agencies in Europe may be more conservative

than CMS. For example, a number of cancer drugs have been approved for reimbursement in the United States

but have not been approved for reimbursement in certain European countries.

Outside the United States, certain countries, including a number of member states of the European Union, set

prices and reimbursement for pharmaceutical products, with limited participation from the marketing

authorization holders. We cannot be sure that such prices and reimbursement will be acceptable to us or our

collaborators. If the regulatory authorities in these jurisdictions set prices or reimbursement levels that are not

commercially attractive for us or our collaborators, our revenues from sales by us or our collaborators, and the

potential profitability of our drug products, in those countries would be negatively affected. An increasing number

of countries are taking initiatives to attempt to reduce large budget deficits by focusing cost-cutting efforts on

pharmaceuticals for their state-run health care systems. These international price control efforts have impacted

all regions of the world but have been most drastic in the European Union. Additionally, some countries require

approval of the sale price of a product before it can be marketed. In many countries, the pricing review period

begins after marketing or product licensing approval is granted. As a result, we might obtain marketing approval

for a product in a particular country, but then may experience delays in the reimbursement approval of our

product or be subject to price regulations that would delay our commercial launch of the product, possibly for

lengthy time periods, which could negatively impact the revenues we are able to generate from the sale of the

product in that particular country.

Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or

reduce healthcare costs may cause such organizations to limit both coverage and level of reimbursement for

new products approved and, as a result, they may not cover or provide adequate payment for our product

candidates. The Inflation Reduction Act, or IRA, enacted in August 2022 allows HHS to negotiate the price of

certain drugs and biologics that CMS reimburses under Medicare Part B and Part D. The IRA’s negotiation

program will apply to high-expenditure single-source drugs that have been approved for at least 7 years (11

years for biologics), among other negotiation selection criteria. The negotiated prices, which became effective in

2026 for the first round of selected drugs, are capped at a statutorily-determined ceiling price. The IRA also

penalizes drug manufacturers that increase prices of Medicare Part B and Part D drugs at a rate greater than the

rate of inflation. In addition, the law eliminates the “donut hole” under Medicare Part D beginning in 2025 by

significantly lowering the beneficiary maximum out-of-pocket cost and requiring manufacturers to subsidize,

through a newly established manufacturer discount program, once the out-of-pocket maximum has been

reached. The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as

opposed to regulation, for the initial years. Manufacturers that fail to comply with the IRA may be subject to

various penalties, including civil monetary penalties. These IRA provisions have begun to take effect

progressively starting in 2023, although the drug negotiation provisions of the IRA are currently the subject of

legal challenges. The effects of the IRA on our business and the healthcare industry in general are not yet

known. In addition, the Center for Medicare and Medicaid Innovation, or CMMI, has announced two new

mandatory models that propose MFN pricing for certain products covered by Medicare and one new voluntary

model that proposes MFN pricing for products covered by Medicaid. These models, or other models announced

by CMMI, could result in significantly lower prices for our products. These laws and regulations may result in

additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for

any of our products for which we may obtain regulatory approval or the frequency with which any such product is

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prescribed or used. At the state level, legislatures are increasingly passing legislation and implementing

regulations designed to control pharmaceutical and biological 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 importing from other countries and bulk

purchasing. Officials appointed by the current presidential administration to oversee the implementation of the

IRA may take a different approach, and the administration and Congress could also pursue statutory changes to

the program, either of which could negatively affect our revenues.

We expect to experience pricing pressures in connection with the sale of any of our product candidates due to

the trend toward managed healthcare, the increasing influence of health maintenance organizations and

additional legislative changes. The downward pressure on healthcare costs in general, particularly prescription

drugs, surgical procedures and other treatments, has become very intense. As a result, increasingly high barriers

are being erected to the entry of new products in the marketplace.

Government policies, including relating to manufacturing, export controls, or tariffs, and negative public

perception regarding vaccines and mRNA-based therapeutics could severely and adversely impact the

manufacturing and sales of our COVID-19 vaccine and other product candidates we may develop, if

approved.

There is a heightened risk that vaccines could be subject to export controls, adverse emergency actions or

supply requirements by governmental and other authorities. In the past, the European Union and other regions

have imposed, or threatened to impose, export controls that would limit or block the delivery of COVID-19

vaccines manufactured in or outside their territories in instances where manufacturers have been delayed or

have not fully satisfied their delivery obligations to such governments, which could have prohibited us from

delivering our COVID-19 vaccine to other jurisdictions. Recently, trade and tariff policies among the United

States and other countries have been unsettled and are subject to frequent changes. The U.S. government has

imposed tariffs and other trade restrictions on goods across a range of industries, and such actions have at

times prompted retaliatory measures by affected countries such as China, Canada and the European Union.

While tariffs with certain countries have been temporarily reduced or paused, the imposition of new tariffs will

likely be met with further reciprocal tariffs, thus increasing the possibility of a global trade war. If trade restrictions

or tariffs reduce global economic activity, potential impacts could include declining sales; increased costs;

volatility in foreign exchange rates; and a decline in the value of our financial assets. Issued or future executive

orders or other new or changes in laws, regulations or policy regarding tariffs could have a material adverse

effect on our business, earnings and financial guidance. The actual impact of the new tariffs on our business is

subject to a number of factors including, but not limited to, restrictions on trade, the effective date and duration of

such tariffs, countries included in the scope of tariffs, changes to amounts of tariffs, potential retaliatory tariffs

imposed by other countries, and the extent to which tariffs are imposed on finished or unfinished pharmaceutical

products. Vaccines are also at risk of being subject to adverse emergency actions taken by governmental

entities in certain countries, including intellectual property expropriation, compulsory licenses, strict price controls

or other actions, such as the requirement that specific quantities of vaccine doses be set aside for designated

purposes or geographic areas. Additional changes in governmental policy preferences and regulatory decision-

making may have an adverse effect on our ability to commercialize products or, if approved, product candidates.

For example, the FDA’s approval of our LP.8.1-adapted monovalent COVID-19 vaccine is in a narrower

population than our previous variant-adapted vaccines.

Furthermore, public sentiment regarding commercialization of vaccines, the safety and efficacy of our COVID-19

vaccine, other COVID-19 vaccines and treatments, and other public perceptions and misinformation relating to

COVID-19, mRNA technology, and our and other COVID-19 vaccines may limit our ability to generate income

from sales of our COVID-19 vaccine and other product candidates we may develop and sell, including due to

changes in local, national and state government policies in the U.S. and other jurisdictions, and cause

reputational damage.

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We face significant competition with other makers of COVID-19 vaccines and may be unable to maintain

a competitive market share for our COVID-19 vaccine.

A number of competitors currently have programs to develop COVID-19 vaccine candidates, including vaccines

developed by Moderna, Inc. and Novavax, Inc. Our competitors pursuing vaccine candidates may have greater

financial, product candidate development, manufacturing and marketing resources than we do. Larger

pharmaceutical and biotechnology companies have extensive experience in clinical testing and obtaining

regulatory approval for their products, and may have the resources to invest heavily to accelerate discovery and

development of their vaccine candidates.

Our efforts to continue successful commercialization of our COVID-19 vaccine may fail if competitors develop

and commercialize COVID-19 vaccines that are safer, more effective, produce longer immunity against

COVID-19, require fewer administrations, have fewer or less severe undesirable effects, have broader market

acceptance, are more convenient to administer or distribute or are less expensive than any vaccine candidate

that we have developed or we may develop.

Our COVID-19 vaccine is sensitive to temperature, shipping and storage conditions and could be subject

to risk of loss or damage.

Our COVID-19 vaccine is, and other product candidates we develop could be, sensitive to temperature, storage

and handling conditions. In particular, while we have improved the required shipping and storage conditions of

our COVID-19 vaccine, it must be shipped and stored at cold temperatures. Loss in supply of our COVID-19

vaccine and our product candidates could occur if the product or product intermediates are not stored or handled

properly. Shelf life for our product candidates may vary by product, and it is possible that supply of our COVID-19

vaccine or our product candidates could be lost due to expiration prior to use. This has in the past led, and could

in the future lead, to additional manufacturing costs and delays in our ability to supply required quantities for

clinical trials or for commercial purposes. Such distribution challenges may make our COVID-19 vaccine a less

attractive product than other COVID-19 vaccines that do not require as cold storage, and our COVID-19 vaccine

may become increasingly less competitive as additional other vaccines become authorized for emergency use. If

we, our partners and customers are unable to adequately manage these issues, we may be exposed to product

liability claims and the market opportunity for our COVID-19 vaccine may be reduced, each of which could

adversely affect our business prospects and materially harm our financial condition.

The market opportunities for some of our product candidates may be small due to the rarity of the

disease, or limited to those patients who are ineligible for or have failed prior treatments. As the target

patient populations for some of our programs are small, we may be unable to achieve or maintain

profitability in future periods without obtaining regulatory approval for additional indications.

The FDA often approves new cancer therapies initially only for use by patients with relapsed or refractory

advanced cancer. We expect to seek approval initially for some of our product candidates in this context.

Subsequently, for those products that prove to be sufficiently beneficial, we would expect to seek approval in

earlier lines of treatment and potentially as a first-line therapy, but there is no guarantee that our product

candidates, even if approved, would be approved for earlier lines of therapy, and, prior to any such approvals,

we may have to conduct additional clinical trials. We are also developing product candidates for the treatment of

rare diseases.

Our projections of the number of people who have or will have the diseases we may be targeting may prove to

be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The

number of trial participants may turn out to be lower than expected. Additionally, the potentially addressable

patient population for our product candidates may be limited or may not be amenable to treatment with our

product candidates. Even if we obtain significant market share for our products, if approved, because the

potential target populations may be small, we may be unable to achieve or maintain profitability in future periods

without obtaining regulatory approval for additional indications.

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If we are unable to continue to increase our marketing and sales capabilities on our own or through third

parties, we may not be able to market and sell our product candidates effectively in the United States

and other jurisdictions, if approved, or generate sufficient product sales revenue.

We have only relatively recently developed our sales, distribution or marketing capabilities in Germany and

Türkiye. With respect to our COVID-19 vaccine, we rely heavily on the sales, distribution, and marketing

capabilities of our partners, except in Germany and Türkiye. To successfully commercialize any other products

that may result from our development programs, several of which are undergoing pivotal clinical trials, we will

need to continue developing sales and marketing capabilities in the United States, Europe and other regions,

either on our own or with others. We may enter into collaborations with other entities to utilize their mature

marketing and distribution capabilities, but we may be unable to enter into marketing agreements on favorable

terms, if at all. If our current and future collaborators do not commit sufficient resources to further commercialize

our COVID-19 vaccine and our future products, if any, and we are unable to develop the necessary marketing

capabilities on our own, we may be unable to generate sufficient product sales revenue to sustain our business.

We compete with many companies that currently have extensive and well-funded marketing and sales

operations. Without continuing to grow our internal team or obtaining the support of third parties to perform

marketing and sales functions, we may be unable to compete successfully against these more established

companies.

Our ability to achieve or maintain profitability in future periods depends in part on our and our

collaborators’ ability to penetrate global markets, where we would be subject to additional regulatory

burdens and other risks and uncertainties associated with international operations that could materially

adversely affect our business.

Our ability to achieve or maintain profitability in future periods will depend in part on our ability and the ability of

our collaborators to commercialize any products that we or our collaborators may develop in markets throughout

the world. Commercialization of products in various markets could subject us to risks and uncertainties,

including:

–obtaining, on a country-by-country basis, the applicable marketing authorization from the competent regulatory

authority;

–the burden of complying with complex and changing regulatory, tax, accounting, labor and other legal

requirements in each jurisdiction that we or our collaborators pursue;

–reduced protection for intellectual property rights;

–differing medical practices and customs affecting acceptance in the marketplace;

–import or export licensing requirements;

–governmental controls, trade restrictions or changes in tariffs;

–economic weakness, including inflation, or political instability;

–production shortages resulting from any events affecting raw material supply or manufacturing capabilities

abroad;

–longer accounts receivable collection times;

–longer lead times for shipping;

–language barriers;

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–foreign currency exchange rate fluctuations;

–the impact of epidemics, pandemics and other public health developments, such as COVID-19, on employees

and the global economy;

–reimbursement, pricing and insurance regimes; and

–the interpretation of contractual provisions governed by local laws in the event of a contract dispute.

We do not have prior experience in all of these areas, and the experience we do have in some of these areas is

limited. Our collaborators may have limited experience in these areas as well. Failure to successfully navigate

these risks and uncertainties may limit or prevent market penetration for any products that we or our

collaborators may develop, which would limit their commercial potential and our revenues.

Even if we obtain regulatory approval for our product candidates, the products may not gain the market

acceptance among physicians, patients, hospitals, treatment centers and others in the medical

community necessary for commercial success.

Even with the requisite approvals, the commercial success of our products will depend in part on the medical

community, patients, and third-party or governmental payors accepting immunotherapies in general, and our

products in particular, as medically useful, cost-effective and safe.

Any product that we bring to the market may not gain market acceptance by physicians, trial participants, third-

party payors, and others in the medical community. Additionally, ethical and legal concerns and social

preferences about research involving mRNA could result in additional regulations restricting or prohibiting the

products and processes we may use. If these products do not achieve an adequate level of acceptance, we may

not generate significant product sales revenue and may not be able to achieve or maintain profitability in future

periods. The degree of market acceptance of our product candidates, if approved for commercial sale, will

depend on a number of factors, including:

–the potential efficacy and potential advantages over alternative treatments;

–the ability to offer our products, if approved, at competitive prices;

–the prevalence and severity of any undesirable effects, including any limitations or warnings contained in a

product’s approved labeling;

–the prevalence and severity of any undesirable effects resulting from checkpoint inhibitors or other drugs or

therapies with which our products are administered;

–the relative convenience and ease of transportation, storage and administration;

–any restrictions on the use of our products, if approved, together with other medications;

–the willingness of the target patient population to try new therapies, such as mRNA vaccines and therapies,

and of physicians to prescribe these therapies;

–the strength of marketing and distribution support and timing of market introduction of competitive products;

–the extent to which changes in local, national and state government policy preferences in the United States

and other jurisdictions resulting from new elected leadership and evolving public sentiment affect demand for

COVID-19 vaccines or mRNA therapeutics and our ability to successfully commercialize our product

candidates, if approved;

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–publicity concerning our products or competing products and treatments; and

–sufficient third-party insurance coverage or reimbursement, and patients’ willingness to pay out-of-pocket in

the absence of third-party coverage or adequate reimbursement.

Even if a potential product displays a favorable efficacy and safety profile in preclinical studies and clinical trials,

market acceptance of the product will not be known until after it is launched. Our efforts to educate the medical

community and third-party payors on the benefits of the products may require significant resources and may

never be successful. Our efforts to educate the marketplace may require more resources than are required by

the conventional technologies marketed by our competitors due to the complexity and uniqueness of our

programs.

In addition, for our products that are approved for marketing, we and/or our collaborator are subject to significant

regulatory obligations regarding the submission of safety and other post-marketing information and reports for

such product, and will need to continue to comply (or ensure that our third-party providers comply) with current

GMP and current good clinical practices, or GCP, for any clinical trials that we or a collaborator conduct post-

approval. In addition, there is always the risk that we or a collaborator or regulatory authority might identify

previously unknown problems with a product post-approval, such as adverse events of unanticipated severity or

frequency. Compliance with these requirements is costly, and any such failure to comply or other issues with our

product candidates identified post-approval could have a material adverse impact on our business, financial

condition and results of operations.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product

candidates, which could make it difficult for us to sell our product candidates, if approved, profitably.

Successful sales of our product candidates, if approved, depend on the availability of coverage and adequate

reimbursement from third-party payors including governmental healthcare programs, such as Medicare and

Medicaid in the United States, managed care organizations and commercial payors, among others. Significant

uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain

regulatory approval. In addition, because certain of our product candidates represent new approaches to the

treatment of cancer, we cannot accurately estimate the potential revenue from our product candidates.

Patients who are provided medical treatment for their conditions generally rely on third-party payors to reimburse

all or part of the costs associated with their treatment. Obtaining coverage and adequate reimbursement from

third-party payors is critical to new product acceptance.

Third-party payors decide which drugs and treatments they will cover and the amount of reimbursement.

Reimbursement by a third-party payor may depend upon a number of factors, including, but not limited to, the

third-party payor’s determination that use of a product is:

–a covered benefit under its health plan;

–safe, effective and medically necessary;

–appropriate for the specific patient;

–cost-effective; and

–neither experimental nor investigational.

Obtaining coverage and reimbursement of a product from a government or other third-party payor is a time-

consuming and costly process that could require us to provide to the payor supporting scientific, clinical and

cost-effectiveness data for the use of our products. Third-party payors could require us to conduct additional

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studies, including post-marketing studies related to the cost effectiveness of a product, to qualify for

reimbursement, which could be costly and divert our resources. Even if we obtain coverage for a given product,

if the resulting reimbursement rates are insufficient, hospitals may not approve our product for use in their facility

or third-party payors may require co-payments that patients find unacceptably high. Patients are unlikely to use

our product candidates unless coverage is provided and reimbursement is adequate to cover a significant

portion of the cost of our product candidates. Separate reimbursement for the product itself may or may not be

available. Instead, the hospital or administering physician may be reimbursed only for providing the treatment or

procedure in which our product is used. Further, from time to time, CMS revises the reimbursement systems

used to reimburse healthcare providers, including the Medicare Physician Fee Schedule and Outpatient

Prospective Payment System, which may result in reduced Medicare payments. In some cases, private third-

party payors rely on all or portions of Medicare payment systems to determine payment rates. Changes to

government healthcare programs that reduce payments under these programs may negatively impact payments

from private third-party payors, and reduce the willingness of physicians to use our product candidates.

In the United States, no uniform policy of coverage and reimbursement for products exists among third-party

payors. Therefore, coverage and reimbursement for products can differ significantly from payor to payor. Further,

one payor’s determination to provide coverage for a product does not assure that other payors will also provide

coverage for the product. Adequate third-party reimbursement may not be available to enable us to maintain

price levels sufficient to realize an appropriate return on our investment in product development.

We intend to seek approval to market our product candidates in the United States, the European Union and

other selected jurisdictions. If we obtain approval for our product candidates in any particular jurisdiction, we will

be subject to rules and regulations in that jurisdiction. In some countries, particularly those in Europe, the pricing

of biologics is subject to governmental control. In these countries, pricing negotiations with governmental

authorities can take considerable time after obtaining marketing approval of a product candidate. Some of these

countries may require the completion of clinical trials that compare the cost-effectiveness of a particular product

candidate to currently available therapies. Other member states allow companies to fix their own prices for

medicines, but monitor and control company profits. The downward pressure on health care costs has become

very intense. As a result, increasingly high barriers are being erected to the entry of new products into the

marketplace. In addition, in some countries, cross-border imports from low-priced markets exert a commercial

pressure on pricing within a country.

The marketability of any product candidates for which we receive regulatory approval for commercial sale may

suffer if government and other third-party payors fail to provide coverage and adequate reimbursement. We

expect downward pressure on pharmaceutical pricing to continue. Further, coverage policies and third-party

reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained

for one or more products for which we receive regulatory approval, less favorable coverage policies and

reimbursement rates may be implemented in the future.

The advancement of healthcare reform legislation and changes to the regulatory environment in the

United States, the European Union and elsewhere may increase the difficulty and cost for us to obtain

marketing approval of and commercialize any product candidates we or our collaborators develop and

may adversely affect the prices for such product candidates.

In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare

costs.

In August 2022, the IRA was enacted, which sets forth meaningful changes to drug product reimbursement by

Medicare. The IRA is anticipated to have significant effects on the pharmaceutical industry and may reduce the

prices we can charge and reimbursement we can receive for our products in the United States, among other

effects. Any reduction in reimbursement from Medicare resulting from the IRA or other legislative or policy

changes or from other government programs may result in a similar reduction in payments from private payers.

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On August 16, 2024, CMS announced the results of a first round of discounted prices effectively set by CMS

under the IRA, applicable to ten products of other manufacturers; those discounted prices, set to take effect for

calendar year 2026, were as high as 79% from 2023 list prices. Additional products will be discounted in future

years. We cannot be sure whether additional legislative changes will be enacted, or the effect of forthcoming

guidance implementing the IRA, or what the impact of such changes on our products and product candidates

may be. Officials appointed by the current presidential administration to oversee the implementation of the IRA or

other statutes may take a different approach, and the administration and Congress could also pursue statutory

changes to this or other programs, either of which could negatively affect our revenues.

The delivery of healthcare in the European Union, including the establishment and operation of health services

and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than

European Union, law and policy. National governments and health service providers have different priorities and

approaches to the delivery of healthcare and the pricing and reimbursement of products in that context. In

general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions

on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-

increasing European Union and national regulatory burdens on those wishing to develop and market products,

this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval

activities, and affect our ability to commercialize any products for which we obtain marketing approval.

We expect that additional healthcare reform measures or proposals will be adopted in the future, any of which

could limit the amounts that governments will pay for healthcare products and services, including public health

measures, which could result in reduced demand for our products and product candidates or additional pricing

pressures. In the event that the pricing structures for healthcare products, such as the product candidates we are

developing, change materially and limit payments for such product candidates, our business will be adversely

impacted as our products may no longer be commercially viable based on their expected net present value; we

may have invested significant resources in product candidates that cannot be commercially developed; or we

may determine that assets that have reached an early phase of development cannot or will not be taken into

further development, notwithstanding their clinical viability. In addition, development assets or clinical programs

that are part of our collaborations may no longer be deemed commercially viable to pursue based on our

collaborators’ assessments of the impact of any proposed, announced, or legislated pricing reforms.

We cannot predict what healthcare reform initiatives may be adopted in the future. Further legislative and

regulatory developments are likely, and we expect ongoing initiatives to increase pressure on drug pricing. Such

reforms could have an adverse effect on anticipated revenues from our approved products and from product

candidates that we may successfully develop and for which we may obtain regulatory approval, and may affect

our overall financial condition and ability to develop product candidates.

Drug marketing and reimbursement regulations in the European Union and elsewhere may materially

affect our ability to market and receive coverage for our products in the member states of the European

Union and elsewhere.

Our COVID-19 vaccine is currently approved in the United States, the European Union, and other jurisdictions,

and we intend to seek approval to market other product candidates in the United States, the European Union

and other selected jurisdictions. If we obtain approval for our products or product candidates in a particular

jurisdiction, we will be subject to rules and regulations in that jurisdiction. In some countries, particularly those in

the European Union, the pricing of biologics is subject to governmental control and other market regulations that

could put pressure on the pricing and usage of our products or product candidates. In these countries, pricing

negotiations with governmental authorities can take considerable time after obtaining marketing approval of a

product candidate. In addition, market acceptance and sales of our product candidates will depend significantly

on the availability of adequate coverage and reimbursement from third-party payors for our product candidates

and may be affected by existing and future healthcare reform measures.

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In addition, in most countries outside the United States, the proposed pricing for a drug must be approved before

it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from

country to country. For example, the European Union provides options for its member states to restrict the range

of medicinal products for which their national health insurance systems provide reimbursement and to control the

prices of medicinal products for human use. Reference pricing used by various member states and parallel

distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices. A

member state may approve a specific price for the medicinal product or it may instead adopt a system of direct

or indirect controls on the profitability of the company placing the medicinal product on the market. In some

countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of

any of our product candidates to other available therapies in order to obtain or maintain reimbursement or pricing

approval. 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 of our products.

Historically, products launched in the European Union do not follow price structures of the United States and,

generally, prices tend to be significantly lower in the European Union. Publication of discounts by third-party

payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of

publication and other countries. If pricing is set at unsatisfactory levels or if reimbursement of our products is

unavailable or limited in scope or amount, our revenues from sales by us or our collaborators and the potential

profitability of any of our product candidates in those countries would be negatively affected.

Risks Related to our Financial Condition and Capital Requirements

Long-term sustainable profitability is difficult to achieve and maintain over time and is highly dependent

on various factors.

Our ability to continue to generate revenues and achieve and maintain long-term sustainable profitability

depends on our ability, alone or with collaborators, to successfully complete the development of, and obtain the

regulatory approvals necessary to commercialize, our product candidates. We continue to generate revenues

from sales of our COVID-19 vaccine and additional limited revenues from other transactions. While we expect to

maintain revenue from ongoing COVID-19 vaccine sales, future demand for COVID-19 vaccination is subject to

uncertainty. Variations driven by factors such as new virus variants, legal developments, policy changes, public

health measures and public sentiment may impact long-term demand of our COVID-19 vaccine. Consequently,

our revenue projections are influenced by this inherent unpredictability. The amount of long-term revenue from

such sales, including the sales of our COVID-19 vaccine, is uncertain at this time. Our ability to generate future

revenues from pharmaceutical product sales and sales of our other products and services depends heavily on

our and our collaborators’ success in:

–completing research and preclinical and clinical development of our product candidates;

–seeking and obtaining U.S. and non-U.S. marketing approvals for product candidates for which we complete

clinical trials;

–seeking and obtaining market access and favorable pricing terms in the United States, the European Union,

and other key geographies;

–furthering the development of our own manufacturing capabilities and manufacturing relationships with third

parties in order to provide adequate (in amount and quality) products and services to support clinical

development and the market demand for our approved products and product candidates, if approved;

–obtaining market acceptance of our approved products and product candidates as a treatment option;

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–launching and commercializing products for which we obtain marketing approval and reimbursement, either

through collaborations or, if launched independently, by establishing a sales force, marketing and distribution

infrastructure;

–addressing any competing technological and market developments, in particular, declining demand for any of

our approved products;

–implementing additional internal systems and infrastructure;

–negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter;

–managing our expenses;

–maintaining, defending, protecting, enforcing and expanding our portfolio of intellectual property rights,

including patents, trade secrets and know-how; and

–attracting, hiring and retaining qualified personnel.

Additionally, we have incurred significant costs associated with the commercialization of our COVID-19 vaccine.

Our expenses could increase beyond our expectations if we are required by the FDA, the European Medicines

Agency, or EMA, or other regulatory agencies to perform clinical and other trials or make changes to our

manufacturing or quality systems in addition to those that we currently anticipate. Accordingly, such costs could

adversely affect our future ability to achieve and maintain profitability.

Our operating results may fluctuate significantly, which makes our future operating results difficult to

predict. If our operating results fall below expectations, the price of the ADSs representing our ordinary

shares could decline.

Our financial condition and operating results have varied in the past and will continue to fluctuate from one

financial period to the next due to a variety of factors, many of which are beyond our control.

Factors relating to our business that may contribute to these fluctuations include the following, as well as other

factors described elsewhere in this report:

–the size and timing of orders for our COVID-19 vaccine;

–delays or failures in advancement of existing or future product candidates into the clinic or in clinical trials;

–the occurrence of adverse events during our clinical trials or post marketing authorization;

–our ability to develop and manufacture our product candidates and commercialize and manufacture our

COVID-19 vaccine and, if approved, our product candidates, at commercial scale, including risks associated

with quality compliance, such as product design, manufacturing processes, supply chain management, and

compliance with regulatory requirements;

–our ability to manage our growth and spending;

–our ability to execute our corporate objectives;

–strategic decisions related to portfolio prioritization, which may result in certain potential one-time effects and

charges and other material adverse effects on our financial condition and results of operations;

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–the outcomes of research programs, clinical trials, or other product development or approval processes

conducted by us and our collaborators;

–the ability of our collaborators to develop and successfully commercialize products developed from our suite of

therapeutic classes;

–our relationships, and any associated exclusivity terms, with collaborators;

–our contractual or other obligations to provide resources to fund our product candidates, and to provide

resources to our collaborators or to the collaborations themselves, including take-or-pay or similar obligations;

–the extent to which we repurchase outstanding ADSs under any share repurchase plans we may enter into in

the future;

–risks associated with the international aspects of our business, including the conduct of clinical trials in

multiple locations, and the risks associated with potential international commercialization, including regulatory

approval, market competition, public sentiment and consumer demand, supply chain disruptions, and changes

to the law and regulatory policy, such as increases in tariffs, in different jurisdictions, such as the United

States;

–our ability to minimize and manage product recalls or inventory losses caused by unforeseen events, cold

chain interruption, testing difficulties or decreased demand, and our ability to write down certain inventory;

–our ability to report our financial results accurately and in a timely manner;

–our dependence on, and the need to attract and retain, key management and other personnel;

–our ability to obtain, protect, maintain, defend and enforce our intellectual property rights;

–our ability to prevent the theft or infringement, misappropriation or other violation of our intellectual property,

trade secrets, know-how or technologies;

–our and our collaborators’ ability to defend against claims of infringement of the intellectual property rights of

third parties;

–potential advantages that our competitors and potential competitors may have in securing funding, obtaining

the rights to critical intellectual property or developing competing technologies or products;

–our ability to obtain additional capital that may be necessary to expand our business;

–our collaborators’ ability to obtain and devote additional capital that may be necessary to develop and

commercialize products under our collaboration agreements, including our COVID-19 vaccine;

–our ability to minimize and manage product liability claims arising from the use of our COVID-19 vaccine and

our product candidates and other future products, if approved;

–business interruptions such as power outages, strikes, acts of terrorism or natural disasters;

–our ability to use our net operating loss carryforwards to offset future taxable income;

–risks of counterparty defaults within our asset management portfolio; and

–increased or unpredictable pricing for the commodities we rely on, including as a result of inflation.

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Each of the factors listed above may be affected by the changing impact of COVID-19 on the global community

and the global economy.

Due to the various factors mentioned above, and others, the results of any of our periods should not be relied

upon as indications of our future operating performance. Our operating results may fluctuate significantly from

one reporting period to the next, such that a period-to-period comparison of our results of operations may not be

a good indication of our future performance.

In any particular period, our operating results could be below the expectations of securities analysts or investors,

which could cause the price of the ADSs to decline. While as a general matter we intend to periodically report on

the status of our product candidate pipeline, including articulating anticipated next steps in the form of

development plans or potential data readouts, we may not always be able to provide forward-looking guidance

on the timing of those next steps. In addition, we do not control the timing of disclosures of any milestones

related to any of our programs that are managed by our collaborators. Any disclosure by a collaborator of data

that are perceived as negative, whether or not such data are related to other data that we or others release, may

have a material adverse impact on the price of the ADSs or our overall valuation. The price of the ADSs may

decline as a result of unexpected clinical trial results in one or more of our programs, including adverse safety

events reported for any of our programs.

We have incurred significant losses in the past and we may incur significant losses in the future.

Prior to the first full year of commercialization of our COVID-19 vaccine, and for the years ended December 31,

2024 and December 31, 2025, we incurred significant losses from operations due to our significant research and

development expenses and our investment in our manufacturing capabilities. Prior to commercialization of our

COVID-19 vaccine, we funded our operations primarily from private placements or issuances of ordinary shares

(including in the form of ADSs) in connection with our public offerings, generation of proceeds under our

collaboration agreements, secured bank loans and issuance of a convertible note.

We have experienced, and we expect to continue to experience, increasing reductions in demand for COVID-19

vaccination generally, including for our vaccine. We expect that future revenues from sales of our COVID-19

vaccine will decrease as demand for vaccination wanes. We plan to continue to invest heavily in research and

development as we make a strong drive to build out our global development organization and diversify our

therapeutic area footprint. Additionally, we plan to enhance capabilities through complementary acquisitions,

technologies, infrastructure and manufacturing. Even for those products for which we have obtained or may

obtain regulatory approval or emergency use authorization, our future revenues will depend upon the size of any

markets in which such products have received approval or authorization to market, our ability to achieve

sufficient market acceptance, reimbursement from third-party payors, and adequate market share in those

markets.

If achieved, profitability is difficult to maintain over time and is highly dependent on various factors. Our future

financial results will depend, in part, on the rate of our future expenditures, the extent to which we experience

long-term success of our commercial products and our ability to obtain funding through revenue from commercial

sales, equity or debt financings, sales of assets, collaborations or grants.

As part of our capital allocation strategy, we expect to continue to incur significant and increasing operating

expenses for the foreseeable future. We anticipate that our expenses will increase substantially if and as we and

our collaborators:

–continue, expand, or modify the research or development of our programs in preclinical development;

–continue, expand, or modify the scope of our clinical trials for our product candidates;

Annual Report on Form 20-F for the year ended December 31, 2025


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–initiate additional preclinical, clinical, or other trials for our product candidates, including under our

collaboration agreements;

–execute on our strategic decisions related to portfolio prioritization, which may result in certain potential one-

time effects and charges and other material adverse effects on our financial condition and results of

operations;

–continue to invest in our immunotherapy platforms to conduct research to identify novel technologies;

–change our manufacturing capacity or capability;

–change or add additional suppliers;

–make changes to our infrastructure in connection with our quality control, quality assurance, legal, compliance

and other groups to support our operations as a public company and our product development and

commercialization efforts, including changes to our sites globally;

–attract and retain skilled personnel;

–seek marketing approvals and reimbursement for our product candidates;

–develop our sales, marketing, and distribution infrastructure for our COVID-19 vaccine and any other products

for which we may obtain marketing approval or emergency use authorization;

–seek to identify and validate additional product candidates;

–acquire or in-license other product candidates and technologies;

–acquire other companies;

–make milestone or other payments under any in-license agreements;

–maintain, protect, defend, enforce and expand our intellectual property portfolio; and

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

The amount of, and our ability to use, net operating losses and research and development credits to

offset future taxable income may be subject to certain limitations and uncertainty. In addition, pending

and future tax audits within our Group, disputes with tax authorities and changes in tax law or fiscal

regulations could lead to additional tax liabilities. We are subject to routine tax audits by the respective

local tax authorities. Any additional tax liability could have an adverse effect on our business, financial

conditions, results of operations or prospects.

In Germany, we have unused German tax loss carryforwards for corporate taxes for German group entities with

pre tax group losses, though we generally have not recognized deferred tax assets related to such loss

carryforwards for International Financial Reporting Standards, or IFRS, reporting purposes as of December 31,

2025. Deferred tax assets are recognized for unused tax losses only to the extent that it is probable that taxable

profit will be available against which the losses can be utilized. In general, net operating loss, or NOL,

carryforwards in Germany do not expire. Furthermore, under current German tax laws, certain substantial

changes in the Company’s ownership and business may further limit the amount of NOL carryforwards that can

be used annually to offset future taxable income.

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For the German tax group, we incurred tax losses up to and including December 31, 2020. Even though we

recognized deferred tax assets on a majority of German tax loss carry forwards in 2020 which were fully utilized

in 2021, they are, however, subject to review and possible adjustment by the German tax authorities. In addition,

the incurred tax losses up to and including December 31, 2024 also remain subject to review.

In addition, we have U.S. federal and state NOL carryforwards due to our subsidiaries in the United States,

which may be subject to limitations on use after an ownership change.

We may not be able to utilize a material portion of our historic or current NOLs or credits in either Germany

(resulting from our German tax group or non-tax group entities in Germany) or the United States until these have

been finally assessed by the tax authorities or when the limitation period has passed. In addition, the rules

regarding the timing of revenue and expense recognition for tax purposes in connection with various transactions

are complex and uncertain in many respects, and, if challenged, our recognition may be subject to a revised

assessment. In the event any such challenge is sustained, our NOLs could be materially reduced or we could be

determined to be a material cash taxpayer for one or more years, which could have an adverse effect on our

business, financial conditions, results of operations or prospects.

Furthermore, our ability to use our NOLs or credits is conditioned upon our attaining profitability and generating

taxable income. Taxable income exceeding NOLs will be subject to taxation resulting in tax liabilities. As

described above, we incurred significant net losses in every year since our inception other than 2018, 2021,

2022 and 2023 and anticipate that in the future, we may incur losses for the majority of the group entities. Our

ability to utilize our NOL or credit carryforwards in the United States and for some other group entities is

uncertain. Therefore, we do not recognize deferred tax assets on NOLs and tax credit carryforwards in the

United States, as the requirements of IAS 12 are not fulfilled.

Under German tax laws, we are obligated to withhold a percentage of wage tax and social security

contributions on personnel expenses if contract services providers are considered to be our internal

employees and remit those withholdings to German tax authorities and social security institutions. Late

payments may subject us to penalties and fees.

Under German tax and social security laws, we are obligated to withhold a percentage of payments we make to

third parties in consideration of the services provided, in case these are considered employment payments, and

remit those withholdings to German tax authorities and social security institutions. After a significant volume of

service providers were engaged to assist with research, development, manufacturing and supply of our

COVID-19 vaccine, we discovered after internal review that we and certain of our subsidiaries did not withhold,

report and remit certain German wage taxes and social security contributions in connection with certain contract

service providers engaged in a manner comparable to internal employees, which we notified tax authorities

about. If we do not properly and timely make required payments in the future, we could be subjected to fees,

administrative offenses or other proceedings or penalties.

It is not possible to seek the refund of these wage taxes or social security contributions from either the German

tax authorities or social security institutions after filing returns. In Germany, employers are considered

secondarily liable for wage taxes.

In addition, value added taxes, or VAT, on invoices received by contract services providers who are considered

internal employees are considered non-deductible and must be repaid to the German tax authorities. It is

possible to reclaim the VAT repaid to the German tax authorities from the service provider. There is a possibility

that the relevant input VAT claims against the contract service providers may, in some instances, not be

enforceable as a result of a contract service provider no longer existing, the lapse of time or any other facts

preventing the enforcement of such claims.

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We may require substantial additional financing to achieve our goals, and a failure to obtain this capital

on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product

development programs, commercialization efforts or other operations.

Our operating plans may change as a result of many factors currently unknown to us, and we may need to seek

additional funds sooner than planned, through public or private equity or debt financings, government or other

third-party funding, sales of assets, marketing and distribution arrangements, other collaborations and licensing

arrangements, or a combination of these approaches. We may require additional capital to obtain regulatory

approval for, and to commercialize, future product candidates. Even if we believe we have sufficient funds for our

current or future operating plans, we may seek additional capital if market conditions are favorable or if we have

specific strategic considerations. Our spending will vary based on new and ongoing development and corporate

activities. Due to the high uncertainty of the length of time and activities associated with discovery and

development of our product candidates, we are unable to estimate the actual funds we will require for

development, marketing and commercialization activities.

Our future funding requirements, both near and long term, will depend on many factors, including, but not limited

to:

–the initiation, progress, timing, costs, and results of preclinical or nonclinical studies and clinical trials for our

product candidates;

–the amount and timing of revenues and associated costs from sales of our COVID-19 vaccine;

–the results of research and our other platform activities;

–the clinical development plans we establish for our product candidates;

–the terms of any agreements with our current or future collaborators, and the achievement of any milestone

payments under such agreements to be paid to us or our collaborators;

–the terms of any other strategic transactions, including relating to any acquisitions, into which we enter;

–the number and characteristics of product candidates that we develop or may in-license;

–the outcome, timing and cost of meeting regulatory requirements established by the FDA, the EMA and other

comparable regulatory authorities;

–the cost of filing, prosecuting, obtaining, maintaining, protecting, defending and enforcing our patent claims

and other intellectual property rights, including actions for patent and other intellectual property infringement,

misappropriation and other violations brought by third parties against us regarding our products or product

candidates or actions by us challenging the patent or intellectual property rights of others;

–the effect of competing technological and market developments, including other products that may compete

with one or more of our product candidates;

–the cost and timing of completion and further expansion of clinical and commercial scale manufacturing

activities sufficient to support all of our current and future programs, including the development of modular

production and clinical facilities in various markets via our BioNTainer network; and

–the cost of establishing sales, marketing, and distribution capabilities for any product candidates for which we

may receive marketing approval and reimbursement in regions where we choose to commercialize our

products on our own.

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To date, we have financed our operations primarily through the sale of equity securities, revenue from

collaborations, and revenue from sales of our COVID-19 vaccine. While we are currently generating product

sales and royalty revenue to finance our operations, we cannot be certain that we will continue to generate

sufficient revenue from product sales and royalties to finance our operations. If we were to seek financing from

outside sources, that additional funding may not be available on favorable terms, or at all. Should our revenues

sufficiently decrease in the future, we expect to finance our future cash needs through a combination of product

sales, public or private equity offerings, debt financings, collaborations, licensing arrangements, and other

marketing or distribution arrangements. Any fundraising efforts may divert our management from their day-to-day

activities, which may adversely affect our ability to develop and commercialize our product candidates. In

addition, we cannot guarantee that future financing will be available in sufficient amounts, at the right time, on

favorable terms, or at all, including as a result of the impact that the shift of COVID-19 towards an endemic

phase and other global events, such as political upheavals and economic downturns, may have on the capital

markets.

Negative clinical trial data or setbacks, or perceived setbacks, in our programs or with respect to our technology

could impair our ability to raise additional financing on favorable terms, or at all. Moreover, the terms of any

financing may adversely affect the holdings or the rights of our shareholders, and the issuance of additional

securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of the

ADSs representing our ordinary shares to decline. If we raise additional funds through public or private equity

offerings, the terms of these securities may include liquidation or other preferences that may adversely affect our

shareholders’ rights.

Further, to the extent that we raise additional capital through the sale of ADSs, ordinary shares or securities

convertible or exchangeable into ordinary shares or ADSs, share ownership interests will be diluted. If we raise

additional capital through debt financing, we would be subject to fixed payment obligations and may be subject

to security interests in our assets and covenants limiting or restricting our ability to take specific actions, such as

incurring additional debt, making capital expenditures or declaring dividends. If we raise additional capital

through marketing and distribution arrangements, sales of assets, collaborations, or licensing arrangements with

third parties, we may have to relinquish certain valuable rights to our product candidates, technologies, future

revenue streams or research programs. We also could be required to seek collaborators for one or more of our

current or future product candidates at an earlier stage than otherwise would be desirable or relinquish our rights

to product candidates or intellectual property that we otherwise would seek to develop or commercialize

ourselves. If we are unable to raise additional capital in sufficient amounts, at the right time, on favorable terms,

or at all, we may have to significantly delay, scale back or discontinue the development or commercialization of

one or more of our products or product candidates, or one or more of our other research and development

initiatives. Any of the above events could significantly harm our business, prospects, financial condition and

results of operations, cause the price of the ADSs to decline, and negatively impact our ability to fund operations.

We may encounter difficulties in developing and expanding our company and managing such

development and expansion, which could disrupt our operations.

To manage our anticipated development and expansion, we must continue to implement and improve our

managerial, operational, legal, compliance and financial systems, expand our facilities, and continue to recruit

and train additional qualified personnel. This includes our acquisitions of Biotheus in January 2025 and CureVac

in December 2025, as well as strategic initiatives more generally. In addition, our management may need to

divert a disproportionate amount of its attention away from its day-to-day activities and devote a substantial

amount of time to managing these development activities.

As an evolving biotechnology company, we are actively pursuing drug classes, platforms and product candidates

in many therapeutic areas and across a wide range of diseases. Successfully developing products for, and fully

understanding the regulatory and manufacturing pathways to, all of these therapeutic areas and disease states

requires a significant depth of talent, resources and corporate processes in order to allow simultaneous

Annual Report on Form 20-F for the year ended December 31, 2025


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execution across multiple areas. Due to our limited resources, we may not be able to effectively manage this

simultaneous execution and the expansion of certain operations or recruit and train additional qualified

personnel. This may result in weaknesses in our infrastructure and/or give rise to operational mistakes, legal or

regulatory compliance failures, loss of business opportunities, loss of employees and reduced productivity

among remaining employees. The physical expansion of our operations may lead to significant costs and may

divert financial resources from other projects, such as the development of our product candidates. If our

management is unable to effectively manage our expected development, our expenses may increase more than

expected, our ability to generate or increase our revenue could be reduced and we may not be able to effectively

implement our business strategy. Our future financial performance and our ability to compete effectively and

commercialize our COVID-19 vaccine and our product candidates, if approved, will depend in part on our ability

to effectively manage the current and future development of our company.

We incur significant costs as a result of operating as a public company, and our management is required

to devote substantial time to compliance initiatives. We are subject to financial reporting and other

requirements for which our accounting and other management systems and resources may not be

adequately prepared. We may fail to comply with the rules that apply to public companies, including

Section 404 of the Sarbanes-Oxley Act of 2002, which could result in sanctions or other penalties that

would harm the business.

As a public company, we incur significant legal, accounting and other expenses. The U.S. federal securities laws,

including the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, and rules subsequently implemented by

the SEC and the Nasdaq Stock Market LLC, or Nasdaq, have imposed various requirements on public

companies, including requirements to file annual and event-driven reports with respect to our business and

financial condition, and to establish and maintain effective disclosure and financial controls and corporate

governance practices. Our management and other personnel need to devote a substantial amount of time to

these compliance initiatives. Moreover, these rules and regulations result in substantial legal and financial

compliance costs and have made some activities time-consuming and costly. We may not be able to produce

reliable financial statements or file these financial statements as part of a periodic report in a timely manner with

the SEC or comply with Nasdaq listing requirements. In addition, we could make errors in our financial

statements that could require us to restate our financial statements.

Pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404, we are required to furnish a report by our

management on our internal control over financial reporting, including the attestation report on internal control

over financial reporting issued by our independent registered public accounting firm. To maintain compliance with

Section 404, we document and evaluate our internal control over financial reporting, which is both costly and

challenging. In this regard, we have needed to continue to dedicate internal resources, have engaged outside

consultants, and have adopted a detailed work plan to assess and document the adequacy of internal control

over financial reporting. We will continue to implement 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 in the

future neither we nor our independent registered public accounting firm will be able to conclude within the

prescribed timeframe that our internal control over financial reporting is effective as required by Section 404. This

could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our

financial statements.

Shareholder activism, the current political environment, and the current high level of government intervention

and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to

additional compliance costs and impact the manner in which we operate our business in ways we cannot

currently anticipate. For example, effective March 18, 2026, pursuant to the Holding Foreign Insiders

Accountable Act, directors and officers of foreign private issuers, including us, are required to comply with the

beneficial ownership reporting requirements of Section 16(a) of the Exchange Act. In addition, the SEC has

issued a concept release in June 2025 soliciting comment on potential changes to the regulatory framework

Annual Report on Form 20-F for the year ended December 31, 2025


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applicable to foreign private issuers, including potential modification or elimination of certain accommodations

currently available to foreign private issuers. Our management and other personnel need to devote a substantial

amount of time to these compliance initiatives.

If we identify material weaknesses in our internal control over financial reporting and fail to remediate

such material weaknesses, we may not be able to report our financial results accurately or to prevent

fraud.

Our management is responsible for establishing and maintaining internal control over financial reporting,

disclosure controls, and compliance with the other requirements of the Sarbanes-Oxley Act and the rules

promulgated by the SEC thereunder. Internal control over financial reporting is a process designed to provide

reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements in

accordance with international financial reporting standards. A material weakness is defined as a deficiency, or a

combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility

that a material misstatement of a company’s annual or interim financial statements will not be prevented or

detected by the company’s internal controls on a timely basis.

If we fail to comply with the relevant rules and regulations or otherwise fail to prepare our financial statements in

accordance with international financial reporting standards, a material weakness may arise. If we are unable to

successfully remediate any material weaknesses, our financial statements could contain material misstatements

discovered in the future that could cause us to fail to meet our future reporting obligations and cause the price of

the ADSs to decline.

If we fail to appropriately account for complex terms in our collaboration and licensing agreements, we

could be required to restate our financial statements.

Our collaboration and licensing agreements involve complex terms and significant judgment in determining the

appropriate accounting treatment. The accounting for such agreements is often subject to interpretation and

evolving guidance. If our accounting assessments are later determined to be incorrect, we may be required to

restate previously issued financial statements, which could have a material adverse effect on our financial

condition and results of operations.

We have various international trade obligations, including customs value calculation, customs tariff

number classification and other related securities requirements. Late payments to customs authorities

may subject us to penalties and fees.

Our supply chain, production and distribution network across the globe creates an increasing level of complexity

in customs and foreign trade processes. The requirements for internal control systems are increasing and must

be developed simultaneously. The risk management system for customs and foreign trade, which we are

continuously improving, determines which stakeholders, goods, and means of transport should be examined and

to what extent. These risks include the potential for non-compliance with customs value calculation, customs

tariff number classification, trade restrictions, security regulations as well as the potential failure to facilitate

international trade. We have in the past discovered that certain of our and our subsidiaries’ customs value

calculations were not applied correctly, following which we notified the customs authorities of potential late

payments.

We are, and will likely continue to be, subject to various audits that arise from time to time, including customs

and potential future foreign trade audits. If we do not properly address our international trade and customs

requirements, we could be subjected to penalties and fees.

As a “foreign private issuer,” we are exempt from a number of rules under the U.S. securities laws, as

well as Nasdaq rules, and we are permitted to file less information with the SEC than U.S. companies.

Annual Report on Form 20-F for the year ended December 31, 2025


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This may limit the information available to holders of the ADSs and may make our ordinary shares and

the ADSs less attractive to investors.

We are a “foreign private issuer,” as defined in the rules and regulations of the SEC, and, consequently, we are

not subject to all of the disclosure requirements applicable to companies organized within the United States.

Although the SEC in June 2025 issued a concept release soliciting public comment on the definition of “foreign

private issuer” and has signaled interest in exploring other rules relating to foreign private status, we currently

remain exempt from certain rules under the U.S. Securities Exchange Act of 1934, as amended, or the

Exchange Act, that regulate disclosure obligations and procedural requirements related to the solicitation of

proxies, consents or authorizations applicable to a security registered under the Exchange Act. Effective March

18, 2026, pursuant to the Holding Foreign Insiders Accountable Act, directors and officers of foreign private

issuers, including us, are required to comply with the beneficial ownership reporting requirements of Section

16(a) of the Exchange Act. However, our officers and directors are exempt from the “short-swing” profit recovery

and short sale prohibition provisions of Section 16 of the Exchange Act. Moreover, we are not required to file

periodic reports and financial statements with the SEC as frequently or as promptly as U.S. public companies.

Accordingly, there may be less publicly available information concerning our company than there is for U.S.

public companies.

As a foreign private issuer, we file an Annual Report on Form 20-F within four months of the close of each

financial year ending December 31 and reports on Form 6-K relating to certain material events promptly after we

publicly announce these events. Additionally, we rely on a provision in Nasdaq’s Listed Company Manual that

allows us to follow German company law and European law applicable to European stock corporations in

general, the German Stock Corporation Act (Aktiengesetz), the Council Regulation (EC) No 2157/2001 of

October 8, 2001 on the Statute for a European company (SE), or the SE Regulation, and the German Act on the

Implementation of Council Regulation (EC) No 2157/2001 of October 8, 2001 on the Statute for a European

company (SE) (Gesetz zur Ausführung der Verordnung (EG) NR. 2157/2001 des Rates vom 8. Oktober 2001

über das Statut der Europäischen Gesellschaft (SE)) (SE-Ausführungsgesetz-SEAG), in particular with regard to

certain aspects of corporate governance. This allows us to follow certain corporate governance practices that

differ in significant respects from the corporate governance requirements applicable to U.S. companies listed on

Nasdaq.

For example, we are exempt from regulations of Nasdaq that require a listed U.S. company to:

–have a majority of the board of directors consist of independent directors;

–require non-management directors to meet on a regular basis without management present;

–adopt a code of conduct and promptly disclose any waivers of the code for directors or executive officers that

should address certain specified items;

–have an independent compensation committee;

–have an independent nominating committee;

–solicit proxies and provide proxy statements for all shareholder meetings;

–review related party transactions; and

–seek shareholder approval for the implementation of certain equity compensation plans and issuances of

ordinary shares.

As a foreign private issuer, we are permitted to follow home country practice in lieu of the above requirements.

We therefore continue to follow German corporate governance practices in lieu of the corporate governance

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requirements of Nasdaq in certain respects. In particular, we follow German corporate governance practices in

connection with the distribution of annual and interim reports to shareholders, the application of our code of

conduct to our employees and the Supervisory Board, executive remuneration disclosure, proxy solicitation in

connection with shareholders’ meetings, and obtaining shareholder approval in connection with the

establishment of, or material amendment to, certain equity-based compensation plans.

Our audit committee is required to comply with the provisions of Section 301 of the Sarbanes-Oxley Act and Rule

10A-3 of the Exchange Act, both of which are also applicable to U.S. companies listed on Nasdaq. As we are a

foreign private issuer, however, our audit committee is not subject to additional requirements of Nasdaq

applicable to listed U.S. companies, including an affirmative determination that all members of the audit

committee are “independent,” using more stringent criteria than those applicable to us as a foreign private issuer.

Due to the above exemptions for foreign private issuers, our shareholders will not be afforded the same

protections or information generally available to investors holding shares in public companies organized in the

United States, some investors may find the ADSs less attractive as a result, and there may be a less active

trading market for the ADSs.

We face risks related to catastrophic global events including natural disasters, political crises, or public

health epidemics and pandemics and other public health developments, that could adversely affect our

operations.

Our business could be adversely impacted by the effects of catastrophic global events, including natural

disasters such as an earthquake, fire, hurricane, tornado, flood or significant power outage; public health crises

such as the COVID-19 pandemic; political crises, such as terrorist attacks, war and other political instability,

including the ongoing geopolitical conflicts in the Middle East and Ukraine, and resulting sanctions imposed and

retaliatory actions taken in response to such sanctions; or other catastrophic events.

For example, prolonged or expanded conflicts, and political responses to global actions, could destabilize oil and

gas supply and demand patterns, increase energy volatility and have severe adverse effects on regional and

global supply chains and economies and our business. We also continue to evaluate the impacts that energy

shortages may have on our partners, suppliers and service providers. Were any of these parties to experience

significant impacts from any energy shortage, our business could be materially harmed. We cannot predict with

certainty the impact that volatility in energy prices could have on our or their operations, including on the

manufacturing of our COVID-19 vaccine and the manufacturing and testing of our product candidates.

Although we have generated revenues from sales of our COVID-19 vaccine, there remains uncertainty regarding

other potential effects of COVID-19 on our business. For example, if a new variant of COVID-19 emerges for

which existing vaccines, including our COVID-19 vaccine, are ineffective, infections may become even more

widespread, negatively impact our ability to enroll patients in clinical studies and complete clinical trials on the

timelines we currently anticipate, or result in an economic downturn that could affect demand for our products

and services or our ability to raise capital, which could have a material adverse effect on our business, operating

results and financial condition. Our suppliers, licensors or collaborators could also be disrupted by conditions

related to COVID-19 or other pandemics and epidemics, possibly resulting in disruption to our supply chain,

clinical trials, partnerships or operations.

Our insurance policies are expensive and protect us only from some business risks, which leaves us

exposed to significant uninsured liabilities.

We maintain insurance coverage that we believe is appropriate for our business; however, such coverage

involves significant costs, is increasingly expensive, and does not cover all potential risks, which may expose us

to uninsured or underinsured liabilities. We do not carry insurance for all categories of risk that our business may

encounter and insurance coverage is becoming increasingly expensive. We do not know if we will be able to

maintain existing insurance with adequate levels of coverage, and any liability insurance coverage we acquire in

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the future may not be sufficient to reimburse us for any expenses or losses we may suffer. We currently maintain

insurance coverage for losses relating to property damage, business interruption, transportation, product liability,

cyber matters, clinical trials, and several other areas of coverage. For example, attracting and retaining qualified

individuals to serve on our Supervisory Board and our Management Board requires that we obtain and maintain

adequate director and officer liability insurance, which has increased in cost as our operations have evolved. We

are dedicating resources to exploring additional avenues for more adequate coverage as our business evolves.

However, the coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed

our insurance coverage, our financial condition would be adversely affected. In the event of contamination or

injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources.

Clinical trials or regulatory approvals for any of our product candidates could be suspended, which could

adversely affect our results of operations and business, including by preventing or limiting the development and

commercialization of any product candidates that we or our collaborators may develop.

Adverse developments affecting financial institutions, companies in the financial services industry or

the financial services industry generally, such as actual events or concerns involving liquidity, defaults

or non-performance, could adversely affect our operations and liquidity.

Actual events involving limited liquidity, defaults, non-performance or other adverse developments that affect

financial institutions or other companies in the financial services industry or the financial services industry

generally, or concerns or rumors about any events of these kinds, have in the past and may in the future lead to

market-wide liquidity problems.

There is no guarantee that the U.S. Department of Treasury, the Federal Deposit Insurance Corporation, and

Federal Reserve Board will provide access to uninsured funds in a timely fashion, or at all, in the event of the

closure of banks or financial institutions.

While we maintain our cash and cash equivalents in multiple financial institutions worldwide, our access to our

cash and cash equivalents in amounts adequate to finance our operations could be significantly impaired by the

financial institutions with which we have arrangements directly facing liquidity constraints or failures. In addition,

investor concerns regarding the U.S. or international financial systems could result in less favorable commercial

financing terms, including higher interest rates or costs and tighter financial and operating covenants, or

systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire

financing on acceptable terms or at all. Any material decline in available funding or our ability to access our cash

and cash equivalents could adversely impact our ability to meet our operating expenses, result in breaches of

our contractual obligations or result in violations of federal or state wage and hour laws, any of which could have

material adverse impacts on our operations and liquidity.

Risks Related to the Manufacturing of our COVID-19 Vaccine, our Product Candidates

and Future Pipeline

Our COVID-19 vaccine and product candidates are based on novel technologies and they may be

complex and difficult to manufacture. We may encounter difficulties in manufacturing, product release,

shelf life, testing, storage, supply chain management or shipping. If we or any of the third-party

manufacturers we work with encounter such difficulties, our ability to supply materials for clinical trials

or any approved product could be delayed or stopped.

The manufacturing processes for our COVID-19 vaccine and our product candidates are novel and complex.

Due to the novel nature of this technology and the recency of our experience at larger scale production, we may

encounter difficulties in manufacturing, product release, shelf life, testing, storage and supply chain

management, or shipping. These difficulties could be due to any number of reasons, including, but not limited to,

complexities of producing batches at larger scale, equipment failure, choice and quality of raw materials and

excipients, analytical testing technology, and product instability. In an effort to optimize product features, we have

in the past and may in the future make changes to our product candidates in their manufacturing and stability

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formulation and conditions. This has resulted in the past, and may in the future result, in our having to resupply

batches for preclinical, clinical, or commercial activities when there is insufficient product stability during storage

and insufficient supply. Insufficient stability or shelf life of our products or product candidates could materially

delay our or our collaborators’ ability to continue the clinical trial for that product candidate or require us to begin

a new clinical trial with a newly formulated drug product, due to the need to manufacture additional preclinical,

clinical or commercial supply.

Our rate of innovation is high, which has resulted in, and will continue to cause a high degree of, technology

change that can negatively impact product comparability during and after clinical development. Furthermore,

technology changes may drive the need for changes in, modification to, or the sourcing of, new manufacturing

infrastructure or may adversely affect third-party relationships.

The process to generate mRNA medicines is complex and, if not developed and manufactured under well-

controlled conditions, can adversely impact pharmacological activity. We may encounter difficulties in scaling up

our manufacturing process, thereby potentially impacting clinical and commercial supply. Additionally, for

individualized therapies, we may encounter issues with our ability to timely and efficiently manufacture product

given the on-demand requirements of such therapies, thereby potentially impacting clinical and commercial

supply.

As we continue developing new manufacturing processes for our drug substance and drug product, the changes

we implement to the manufacturing process may impact, in turn, specification and stability of the drug product.

Changes in our manufacturing processes may lead to failure of lots and this could lead to a substantial delay in

our clinical trials or an inability to supply sufficient commercial quantities of drug product. Our mRNA product

candidates may prove to have a stability profile that leads to an unfavorable shelf life. This poses risk in supply

requirements, wasted stock and higher cost of goods.

We are dependent on a number of equipment providers who are also implementing novel technology.

Further, we have developed our own custom manufacturing equipment for certain of our product

candidates. If such equipment malfunctions or we encounter unexpected performance issues, we could

encounter delays or interruptions to clinical and commercial supply.

Due to the number of different programs, we may in the future have cross contamination of products inside of our

factories, CROs, external CMOs, suppliers or in the clinic that affect the integrity of our products. Additionally, for

some programs the manufacturing scale is extremely small compared to the standard volumes of supply, such

that we run the risk of contaminating the process each time we reopen a container to use remaining supplies.

As we scale the manufacturing output for particular programs, we plan to continuously improve yield, purity and

the pharmaceutical properties of our product candidates from IND-enabling studies through commercial launch,

including shelf life stability and solubility properties of drug product and drug substance. Due to continuous

improvement in manufacturing processes, we may switch processes for a particular program during

development. However, after the change in process, more time is required for pharmaceutical property testing,

such as six- or 12- month stability testing. That may require resupplying clinical or commercial material, or

making additional GMP batches to keep up with clinical trial demand before such pharmaceutical property

testing is completed.

We are utilizing a number of raw materials and excipients that are either new to the pharmaceutical industry or

are being employed in a novel manner. Some of these raw materials and excipients have not been scaled to a

level to support commercial supply and could experience unexpected manufacturing or testing failures, or supply

shortages. Such issues with raw materials and excipients could cause delays or interruptions to clinical and

commercial supply of our COVID-19 vaccine and our product candidates. Further, now and in the future, one or

more of our programs may have a single source of supply for raw materials and excipients. Some of our

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suppliers are located in countries different from our manufacturing sites. Export restrictions could lead to

unplanned interruptions in manufacturing, thus impacting supply of both clinical and commercial material.

We have established a number of analytical assays, and may have to establish several more, to assess the

quality of our mRNA products and product candidates. We may identify gaps in our analytical testing strategy

that might prevent release of product or could require product withdrawal or recall. For example, we may

discover new impurities that have an impact on product safety, efficacy or stability. This may lead to an inability to

release mRNA products or product candidates until the manufacturing or testing process is rectified.

Our product and product intermediates are extremely temperature sensitive, and we may learn that any or all of

our products are less stable than desired. We may also find that transportation conditions negatively impact

product quality. This may require changes to the formulation or manufacturing process for one or more of our

products or product candidates and result in delays or interruptions to clinical or commercial supply. In addition,

the cost associated with such transportation services and the limited pool of vendors may also add additional

risks of supply disruptions. As we transport intermediate products with holding times in refrigeration (TIR) and

allowed times out of refrigeration (TOR) across long distances and crossing borders, traffic issues and customs

delays could lead to the loss of batches which would need to be replaced.

Certain of our product candidates are uniquely manufactured for each patient and we may encounter

difficulties in production, particularly with respect to scaling our manufacturing capabilities. If we or any

of the third-party manufacturers with whom we contract encounter these types of difficulties, our ability

to provide such product candidates for clinical trials or, if approved, products for patients could be

delayed or stopped, or we may be unable to maintain a commercially viable cost structure.

We custom design and manufacture certain product candidates that are unique and tailored specifically for each

patient. Manufacturing unique lots of these product candidates is susceptible to product loss or failure due to

issues with:

–logistics associated with the collection of a patient’s tumor, blood or other tissue sample;

–shipping such samples to a facility for genetic sequencing;

–next-generation sequencing of the tumor mRNA;

–biopsy of a sufficient quantity of cancerous tissue to allow for proper sequencing and identification of tumor-

specific mutations;

–identification of appropriate tumor-specific mutations;

–the use of a software program, including proprietary and open source components, which is hosted in the

cloud and a part of our product candidate, to assist with the design of the patient-specific mRNA, which

software must be maintained and secured;

–effective design of the patient-specific mRNA that encodes for the required neoantigens;

–batch-specific manufacturing failures or issues that arise due to the uniqueness of each patient-specific batch

that may not have been foreseen;

–quality control testing failures;

–unexpected failures of batches placed on stability;

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–shortages or quality control issues with single-use assemblies, consumables or critical parts sourced from

third-party vendors that must be changed out for each patient-specific batch;

–significant costs associated with individualized manufacturing that may adversely affect our ability to continue

development;

–successful and timely manufacture and release of the patient-specific batch;

–shipment issues encountered during transport of the batch to the site of patient care;

–the ability to define a consistent safety profile at a given dose when each participant receives a unique

treatment; and

–our reliance on single source suppliers.

We also continue to evolve our own custom manufacturing equipment. This equipment may not function as

designed, which may lead to deviations in the drug product being produced. This can lead to increased batch

failure and the inability to supply patients enrolled in the clinical trial. If our clinical development plans are

expanded, we may not be able to supply this expanded need reliably without significant investments due to the

custom nature of the equipment and single-use assemblies. In addition, there will be considerable time to scale

up our facilities or build new facilities before we can begin to meet any commercial demand if one or more of our

individualized product candidates are approved. This expansion or addition of new facilities could also lead to

product comparability issues, which can further delay introduction of new capacity.

For those of our product candidates that are manufactured for each individual patient, we are required to

maintain a chain of identity with respect to each patient’s tissue sample, the sequenced data derived from such

tissue sample, the results of such patient’s genomic analysis and the custom manufactured product for such

patient. Maintaining such a chain of identity is difficult and complex, and failure to do so could result in product

mix-up, adverse patient outcomes, loss of product, or regulatory action, including withdrawal of any approved

products from the market. Further, as our product candidates are developed through early-stage clinical studies

to later-stage clinical trials towards approval and commercialization, we expect that multiple aspects of the

complicated collection, analysis, manufacture and delivery processes will be modified in an effort to optimize

processes and results. These changes may not achieve the intended objectives, and any of these changes could

cause our product candidates to perform differently than we expect, potentially affecting the results of clinical

trials.

Our inability to manufacture sufficient or appropriate quantities of our COVID-19 vaccine or any of our

product candidates, or our failure to comply with applicable regulatory requirements, could materially

and adversely affect our business.

Manufacturing is a vital component of our individualized immunotherapy approach, and we have invested

significantly in our manufacturing facilities, including the acquisition of a manufacturing site in Marburg, Germany,

the construction of a novel modular manufacturing facility that we refer to as a “BioNTainer,” and the construction

of a facility to support manufacturing of our Individualized Vaccines Against Cancer candidates. All internal

manufacturing is performed under GMP guidelines. We also rely on a network of CMOs for the manufacture of

our COVID-19 vaccine. We do not rely on any external CMOs for the manufacture of our individualized product

candidates and at this time, and we have limited redundancy among our facilities. Due to the individualized

nature of our product candidates, we do not maintain product reserves. If any of our or our external CMOs’

manufacturing facilities, including our BioNTainer units, experience difficulties, including related to

manufacturing, product release, shelf life, testing, storage and supply chain management or shipping, our clinical

development programs may be delayed or suspended until we or our external CMOs can resume operations.

We may also be required to incur significant expenditures to resolve such difficulties.

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We and our collaboration partner also have experienced, and continue to face the risk of, inventory write-downs

or redundant production capacities with respect to our COVID-19 vaccine. Planned new formulations of our

COVID-19 vaccine, including versions that could protect against new variants of COVID-19, have resulted or

may result in significant research and development expense that was not or may not be recouped. In addition,

we have experienced in the past, and may experience in the future, redundant production capacities under our

agreements with CMOs due to planned new formulations, adaptations of our COVID-19 vaccine and increased

internal manufacturing capacities. Significant inventory write-downs or redundant manufacturing expenses would

negatively impact our results of operations.

Our facilities are subject to various regulatory requirements and may be subject to announced or unannounced

inspections by the FDA or other regulatory authorities at any time during the development or commercialization

phase. If we or our external CMOs cannot successfully manufacture material that conforms to our specifications

and the strict regulatory requirements of the FDA, the EMA or comparable regulatory authorities in other

jurisdictions, we may not be able to rely on our or our external CMOs’ manufacturing facilities for the

manufacture of our product candidates. If the FDA, the EMA or another comparable regulatory authority finds our

or our external CMOs’ facilities inadequate for the manufacture of our COVID-19 vaccine or our product

candidates or otherwise deficient, including as a result of a site inspection, such facilities may be the subject of

adverse regulatory action, including the issuance of untitled or warning letters. If such facilities are subject to

enforcement action in the future or are otherwise inadequate, we may need to find alternative manufacturing

facilities, which would significantly delay or otherwise impact our ability to develop, obtain regulatory approval for

or market our COVID-19 vaccine or our product candidates.

Additionally, we may experience manufacturing difficulties due to resource constraints, labor disputes or unstable

political environments. If we were to encounter any of these difficulties, our ability to provide our product

candidates to patients in clinical trials, or to provide approved products for the treatment of patients, would be

jeopardized.

We are subject to regulatory and operational risks associated with the physical and digital infrastructure

at both our internal manufacturing facilities and at those of our external service providers.

The designs of our facilities are based on current standards for biotechnology facilities. They have been

reviewed and approved by local authorities and have also received GMP manufacturing licenses. We have

designed our facilities to incorporate a significant level of automation of equipment with integration of several

digital systems to improve efficiency of operations. We have attempted to achieve a high level of digitization for

clinical and commercial manufacturing facilities relative to industry standards. While this is meant to improve

operational efficiency, this may pose additional risk of process equipment malfunction and even overall

manufacturing system failure or shutdown due to internal or external factors including, but not limited to, design

issues, system compatibility or potential cybersecurity breaches. This may lead to a delay in supply or shutdown

of our facilities. Any disruption in our manufacturing capabilities could cause delays in our production capacity for

our drug substances or drug products, impose additional costs, or require us to identify, qualify and establish an

alternative manufacturing site, the occurrence of which could have a material adverse effect on our business,

financial condition, results of operations and prospects.

As we expand our development and commercial capacity, we may continue to establish additional manufacturing

capabilities in different jurisdictions, which may lead to regulatory delays or prove costly. If we fail to select the

correct location, complete the construction in an efficient manner, recruit required personnel, and/or generally

manage our growth effectively, the development and production of our products or product candidates could be

delayed or curtailed. Additional investments may be needed if changes in our manufacturing process lead to

required changes in our infrastructure.

Our COVID-19 vaccine and certain of our product candidates rely on the availability of specialty raw

materials, which may not be available to us on acceptable terms or at all.

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Our product candidates require many specialty raw materials, some of which are manufactured by small

companies with limited resources and experience to support a commercial product, and suppliers may not be

able to deliver raw materials to our specifications. In addition, some such suppliers normally support blood-based

hospital businesses and generally do not have the capacity to support commercial products manufactured under

GMP by biopharmaceutical firms. These suppliers may be ill-equipped to support our needs, especially in non-

routine circumstances like an FDA inspection or medical crisis, such as widespread contamination. We also do

not have contracts with many of these suppliers, and we may not be able to contract with them on acceptable

terms or at all. Accordingly, we have experienced and we may in the future experience delays in receiving key

raw materials to support clinical or commercial manufacturing.

In addition, some raw materials are currently available from a single supplier, or a small number of suppliers. We

cannot be sure that these suppliers will remain in business or that they will not be purchased by one of our

competitors or another company that is not interested in continuing to produce these materials for our intended

purpose. In addition, the lead time needed to establish a relationship with a new supplier can be lengthy, and we

may experience delays in meeting demand in the event we must switch to a new supplier. The time and effort to

qualify a new supplier could result in additional costs, diversion of resources or reduced manufacturing yields,

any of which would negatively impact our operating results. Further, we may be unable to enter into agreements

with a new supplier on commercially reasonable terms or at all, which could have a material adverse impact on

our business.

We are subject to significant regulatory oversight with respect to manufacturing our products and

product candidates. Our manufacturing facilities or the manufacturing facilities of our third-party

manufacturers or suppliers may not meet regulatory requirements. Failure to meet GMP requirements

set forth in regulations promulgated by the FDA, the EMA and other comparable regulatory authorities

could result in significant delays in and costs of our products.

The manufacturing of immunotherapies for clinical trials or commercial sale is subject to extensive regulation.

GMP requirements govern manufacturing processes and procedures, including record-keeping, and the

implementation and operation of quality systems to control and assure the quality of products and materials used

in our products and product candidates. Poor control of the GMP production processes can lead to product

quality failures that can impact our ability to supply product, resulting in loss of potential product sales revenue,

cost overruns and delays to clinical timelines for our clinical programs, which could be extensive. Such

production process issues include but are not limited to:

–critical deviations in the manufacturing process;

–facility and equipment failures;

–contamination of the product due to an ineffective quality control strategy;

–facility contamination as assessed by the facility and utility environmental monitoring program;

–ineffective process, equipment or analytical change management, resulting in failed lot release criteria;

–raw material failures due to ineffective supplier qualification or regulatory compliance issues at critical

suppliers;

–ineffective product stability;

–failed lot release or facility and utility quality control testing;

–ineffective corrective actions or preventative actions taken to correct or avoid critical deviations due to our

developing understanding of the manufacturing process as we scale; and

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–failed or defective components or consumables.

We must supply all necessary documentation in support of a BLA or other marketing authorization application on

a timely basis and must adhere to the FDA’s, the EMA’s and other countries’ GMP requirements, which are

enforced, in the case of the FDA, in part through its facilities inspection program.

Regulatory authorities typically require representative manufacturing site inspections to assess adequate

compliance with GMPs and manufacturing controls as described in the filing. If either we or one of our third-party

manufacturing sites fail to provide sufficient quality assurance or control, approval to continue delivery of our

commercial product or to commercialize our product candidates may not be granted. Inspections by regulatory

authorities may be announced or unannounced and may occur at any time during the development or

commercialization phase. The inspections may be product-specific or facility-specific for broader GMP

inspections, or as a follow up to market or development issues that the regulatory agency may identify. Deficient

inspection outcomes may result in adverse regulatory action, including the issuance of untitled or warning letters,

which could influence our ability, or the ability of our third-party manufacturers or suppliers, to fulfill supply

obligations, impacting or delaying supply or delaying programs. Our failure, or the failure of our third-party

manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including,

but not limited to, clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals,

license revocation, seizures or recalls of product candidates or products, operating restrictions, and criminal

prosecutions, any of which could significantly and adversely affect supplies of our products and product

candidates (including those of our collaborators) and our overall business operations.

The manufacturing process for any product is subject to the FDA’s, the EMA’s and other regulatory authorities’

approval processes, and we may need to contract with manufacturers whom we believe can meet applicable

regulatory authority requirements on an ongoing basis. If we or our third-party manufacturers are unable to

reliably manufacture to specifications acceptable to the FDA, the EMA or other regulatory authorities, we or our

collaborators may not obtain or maintain the approvals we or they need to release and deliver such products.

Even if we or our collaborators obtain regulatory approval for any of our immunotherapies, there is no assurance

that either we or our CMOs will be able to manufacture our product candidates to specifications acceptable to

the FDA, the EMA or other regulatory authorities, to produce it in sufficient quantities to meet the requirements

for the potential launch of the product, or to meet potential future demand. Any of these challenges could delay

completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase

clinical trial costs, delay approval of our product candidates, impair commercialization efforts or increase our cost

of goods. The occurrence of any of the foregoing could have an adverse effect on our business, financial

condition, results of operations and growth prospects.

In addition, we may not have direct control over the ability of our CMOs to maintain adequate quality control,

quality assurance and qualified personnel. Furthermore, all of our CMOs are engaged with other companies to

supply or manufacture materials or products for such companies, which exposes our CMOs to regulatory risks

for the production of such materials and products. As a result, failure to meet the regulatory requirements for the

production of those materials and products may generally affect the regulatory status of our CMOs’ facilities, and

could result in the sanctions and other adverse outcomes described above. Our potential future dependence

upon others for the manufacture of our products, product candidates and raw materials may adversely affect our

future operating results and our ability to commercialize any products that receive regulatory approval on a

timely and competitive basis.

The FDA, the EMA and other regulatory authorities may require us to submit product samples of any lot of any

approved product together with the protocols showing the results of applicable tests at any time. Under some

circumstances, the FDA or other regulatory authorities may require that we do not distribute a lot or lots until the

relevant agency authorizes such release. Deviations in the manufacturing process, including those affecting

quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures

or product recalls. Our CMOs have, in the past, experienced lot failures and some may have experienced

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product recalls. Lot failures or product recalls with respect to product produced by either our own facilities or

those of our third-party manufacturers could cause us and our collaborators to delay clinical trials, product

launches or product supply, which could be costly to us and otherwise harm our business, financial condition,

results of operations and prospects.

We also may encounter problems hiring and retaining the experienced scientific, quality-control and

manufacturing personnel needed to operate our manufacturing processes and operations, which could result in

delays in production or difficulties in maintaining compliance with applicable regulatory requirements. While we

train and qualify all personnel around the appropriate handling of our products and materials, we may not be

able to control for or ultimately detect intentional sabotage or negligence by any employee or contractor.

Risks Related to our Reliance on Third Parties

We rely on third parties in the conduct of significant aspects of our preclinical studies and clinical trials

and intend to rely on third parties in the conduct of future clinical trials. If these third parties do not

successfully carry out their contractual duties, fail to comply with applicable regulatory requirements or

fail to meet expected deadlines, we may be unable to obtain regulatory approval for our product

candidates.

We currently rely, and expect to continue to rely, on third parties, such as CROs, clinical data management

organizations, collaborators, medical institutions and clinical investigators, to conduct various and significant

elements of our clinical trials. Furthermore, we currently rely, and expect to continue to rely, on third parties to

conduct certain research and preclinical testing activities. In some cases, these third parties may terminate their

engagements with us. If we need to enter into alternative arrangements, it would delay our discovery or product

development activities.

Our reliance on these third parties for research and development activities will reduce our control over these

activities but will not relieve us of our regulatory or contractual responsibilities. We are responsible for ensuring

that each of our preclinical studies and clinical trials is conducted in accordance with the applicable protocol,

legal and regulatory requirements and scientific standards. For example, we are responsible for ensuring that

each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the

trial.

Moreover, the FDA requires us to comply with GCP for conducting, recording and reporting the results of clinical

trials to assure that data and reported results are credible and accurate and that the rights, integrity and

confidentiality of trial participants are protected. We are also required to register ongoing clinical trials and post

the results of completed clinical trials on a U.S. government-sponsored database, ClinicalTrials.gov, within

certain timeframes. Failure to do so can result in fines, adverse publicity, and civil and criminal sanctions. For

any violations of laws and regulations during the conduct of our preclinical studies and clinical trials, we could be

subject to warning letters or enforcement action that may include civil penalties up to and including criminal

prosecution.

We and our CROs are required to comply with regulations, including GCP, for conducting, monitoring, recording

and reporting the results of preclinical studies and clinical trials to ensure that the data and results are

scientifically credible and accurate and that the trial participants are adequately informed, among other things, of

the potential risks of participating in clinical trials. We are also responsible for ensuring that the rights of our

clinical trial participants are protected. These regulations are enforced by the FDA, the regulatory authorities of

the EU member states, and comparable regulatory authorities of other jurisdictions for any product candidates in

clinical development. The FDA enforces GCP regulations through periodic inspections of clinical trial sponsors,

principal investigators and trial sites. If we or our CROs fail to comply with applicable GCP, the clinical data

generated in our clinical trials may be deemed unreliable and the FDA or comparable regulatory authorities of

other jurisdictions may require us to perform additional clinical trials before approving our marketing applications.

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We cannot be sure that, upon inspection, the FDA will determine that any of our future clinical trials will comply

with GCP. In addition, our clinical trials must be conducted with product candidates produced in accordance with

the requirements of GMP regulations. Our failure or the failure of our CROs to comply with these regulations may

require us to repeat clinical trials, which would delay the regulatory approval process and could also subject us

to enforcement action.

Although we have designed, and in the future intend to design the clinical trials for certain of our product

candidates, our collaborators will design the clinical trials that they are managing (in some cases, with our input)

and in the case of clinical trials controlled by us, we expect that CROs will conduct all of the clinical trials. As a

result, many important aspects of our development programs, including their conduct and timing, are outside of

our direct control. Our reliance on third parties to conduct future preclinical studies and clinical trials results in

less direct control over the management of data developed through preclinical studies and clinical trials than

would be the case if we were relying entirely upon our own staff. Communicating with outside parties can also

potentially lead to mistakes as well as difficulties in coordinating activities. Outside parties may:

–have staffing difficulties;

–fail to comply with contractual obligations;

–experience regulatory compliance issues;

–undergo changes in priorities or become financially distressed;

–form relationships with other entities, some of which may be our competitors;

–make human errors; or

–be subject to cyberattacks.

These factors may materially adversely affect the willingness or ability of third parties to conduct our preclinical

studies and clinical trials and may subject us to unexpected cost increases that are beyond our control. If the

CROs do not perform preclinical studies and clinical trials in a satisfactory manner, breach their obligations to us

or fail to comply with regulatory requirements, the development, regulatory approval and commercialization of

our product candidates may be delayed, we may not be able to obtain regulatory approval and commercialize

our product candidates, or our development programs may be materially and irreversibly harmed. If we are

unable to rely on preclinical and clinical data collected by our CROs, we could be required to repeat, extend the

duration of, or increase the size of any clinical trials we conduct and this could significantly delay

commercialization and require significantly greater expenditures.

We also rely on other third parties to transport, store and distribute the required materials for our clinical trials. In

the past, certain of our third-party vendors have mishandled our materials, resulting in loss of full or partial lots of

material. Any further performance failure on the part of these third parties could result in damaged products and

could delay clinical development or marketing approval of any product candidates we may develop or

commercialization of our medicines, if approved, producing additional losses and depriving us of potential

product sales revenue, causing us to default on our contractual commitments, result in losses that are not

covered by insurance, and damage our reputation and overall perception of our products in the marketplace.

Our existing collaborations, or any future collaboration arrangements that we may enter into, may not be

successful, which could significantly limit the likelihood of receiving the potential economic benefits of

the collaboration and adversely affect our ability to develop and commercialize our products and

product candidates.

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We have entered into collaborations under which our collaborators have provided, and may in the future provide,

funding and other resources for developing and commercializing our products and product candidates. We

expect to enter into additional collaborations to access additional funding, capabilities and/or expertise in the

future. Our existing collaborations, and any future collaborations we enter into, may pose a number of risks,

including the following:

–collaborators may not perform or prioritize their obligations as expected;

–the clinical trials conducted as part of such collaborations may not be successful;

–collaborators may not pursue development and commercialization of any product candidates and products

that achieve regulatory approval or may elect not to continue or renew development or commercialization of

programs based on clinical trial results, changes in the collaborators’ focus or available funding (for example,

we are aware that there have been allegations that Fosun International Ltd., an affiliate of our collaboration

partner Fosun Pharma, is facing liquidity risks), or external factors, such as an acquisition, that divert

resources or create competing priorities;

–collaborators may delay clinical trials, provide insufficient funding for clinical trials, stop a clinical trial, abandon

a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate

for clinical testing;

–collaborators could independently develop, or develop with third parties, products that compete directly or

indirectly with our product candidates if the collaborators believe that competitive products are more likely to

be successfully developed or can be commercialized under terms that are more economically attractive than

ours;

–product candidates developed in collaborations with us may be viewed by our collaborators as competitive

with their own product candidates or products, which may cause collaborators to cease to devote resources to

the development or commercialization of our product candidates;

–a collaborator with marketing and distribution rights to one or more of our product candidates that achieve

regulatory approval may not commit sufficient resources to the marketing and distribution of any such product;

–disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or

the preferred course of development of any product candidates, may cause delays or termination of the

research, development or commercialization of such product candidates, may lead to additional

responsibilities for us with respect to such product candidates, or may result in litigation or arbitration, any of

which would be time-consuming and expensive;

–collaborators may not properly maintain, protect, defend or enforce our intellectual property rights or may use

our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our

intellectual property or proprietary information or expose us to potential litigation;

–disputes may arise with respect to the ownership of intellectual property developed pursuant to our

collaborations;

–collaborators may infringe, misappropriate or otherwise violate the intellectual property rights of third parties,

which may expose us to litigation and potential liability;

–collaborations may be terminated for the convenience of the collaborator and, if terminated, the development

of our product candidates may be delayed, and we could be required to raise additional capital to pursue

further development or commercialization of the applicable product candidates;

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–future relationships may require us to incur non-recurring and other charges, increase our near- and long-term

expenditures, issue securities that dilute our existing shareholders, or disrupt our management and business;

–we could face significant competition in seeking appropriate collaborators, and the negotiation process is time-

consuming and complex; and

–our international operations through any future collaborations, acquisitions or joint ventures may expose us to

certain operating, legal and other risks not encountered in Germany or the United States.

If our collaborations do not result in the successful development and commercialization of programs, or if one of

our collaborators terminates its agreement with us, we may not receive any future research funding or milestone,

earn-out, royalty or other contingent payments, or otherwise yield the expected benefits under the collaborations.

As a result, our development of product candidates and commercialization efforts could be delayed and we may

need additional resources to develop and commercialize our product candidates. If one of our collaborators

terminates its agreement with us, we may find it more difficult to attract new collaborators and the perception of

us in the business and financial communities could be adversely affected. All of the risks relating to product

development, regulatory approval and commercialization described in this report apply to the activities of our

collaborators.

If we are not able to establish collaborations on commercially reasonable terms, we may have to alter

our research, development and commercialization plans.

Our research and product development programs and the potential commercialization of any product candidates

we develop alone or with collaborators will require substantial additional cash to fund expenses, and we expect

that we will continue to seek collaborative arrangements with others in connection with the development and

potential commercialization of current and future product candidates or the development of ancillary

technologies. We face significant competition in establishing relationships with appropriate collaborators. In

addition, there have been a significant number of recent business combinations among large pharmaceutical

companies that have resulted in a reduced number of potential future collaborators. Whether or not we reach a

definitive agreement for a collaboration will depend, among other things, upon our assessment of the

collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed

collaborator’s evaluation of a number of factors. Those factors may include, among other things and as

applicable for the type of potential product or technology, an assessment of the opportunities and risks of our

technology, the design or results of studies or trials, the likelihood of approval, if necessary, of the FDA or

comparable regulatory authorities outside the United States, the potential market for the subject product

candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the

potential of competing products and technologies and industry and market conditions generally.

Current or future collaborators may also consider alternative product candidates or technologies for similar

indications that may be available to collaborate on and whether such a collaboration could be more attractive

than the one with us. Additionally, we may be restricted under existing collaboration agreements from entering

into future agreements on certain terms or for certain development activities with potential collaborators. For

example, we have granted exclusive rights or options to Pfizer for certain targets, and under the terms of our

respective collaboration agreements with them, we will be restricted from granting rights to other parties to use

our mRNA technology to pursue potential products that address those targets. Similarly, our collaboration

agreements have in the past and may in the future contain non-competition provisions that could limit our ability

to enter into collaborations with future collaborators.

Collaborations are complex and time-consuming to negotiate and document. We may not be able to negotiate

collaborations on a timely basis, on acceptable terms, or at all. If we do enter into additional collaboration

agreements, the negotiated terms may force us to relinquish rights that diminish our potential profitability from

development and commercialization of the subject product candidates or others. If we are unable to enter into

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additional collaboration agreements, we may have to curtail the research and development of the product

candidate or technology for which we are seeking to collaborate, reduce or delay research and development

programs, delay potential commercialization timelines, reduce the scope of any sales or marketing activities or

undertake research, development or commercialization activities at our own expense. If we elect to increase our

expenditures to fund research, development or commercialization activities on our own, we may need to obtain

additional capital, which may not be available to us on acceptable terms or at all.

We have entered into in-licensing arrangements and may form or seek to enter into additional licensing

arrangements in the future, and we may not realize the benefits of such licensing arrangements.

We are a party to licenses that give us rights to third-party intellectual property, including patents and patent

applications, that are necessary or useful for our business. For example, we have obtained licenses from Acuitas

Therapeutics Inc., or Acuitas, CellScript LLC, or CellScript, and its affiliate, mRNA RiboTherapeutics, Inc., to

patent rights claiming certain uses of modified RNA, as well as licenses from certain other parties for intellectual

property useful in pharmaceutical formulations. We may enter into additional licenses to third-party intellectual

property in the future.

The success of products developed based on in-licensed technology will depend in part on the ability of our

current and future licensors to prosecute, obtain, maintain, protect, enforce and defend patent protection for our

in-licensed intellectual property. Our current and future licensors may not successfully prosecute the patent

applications we license. Even if patents were issued in respect of these patent applications, our licensors may

fail to maintain these patents, may determine not to pursue litigation against other companies that are infringing

these patents, or may pursue such litigation less aggressively than we would. Without protection for the

intellectual property we license, other companies might be able to offer substantially identical products for sale,

which could adversely affect our competitive business position and harm our business prospects. In addition, we

sublicense our rights under various third-party licenses to our collaborators. Any impairment of these sublicensed

rights could result in reduced revenues under our collaboration agreements or result in termination of an

agreement by one or more of our collaborators.

Disputes may also arise between us and our licensors regarding intellectual property subject to a license

agreement, including:

–the scope of rights granted under the license agreement and other interpretation-related issues;

–whether and the extent to which our technology and processes infringe, misappropriate or otherwise violate

the intellectual property of the licensor that is not subject to the licensing agreement;

–our right to sublicense patent and other intellectual property rights to third parties under collaborative

relationships;

–our diligence obligations with respect to the use of the licensed intellectual property and technology in relation

to our development and commercialization of our product candidates, and what activities satisfy those

diligence obligations;

–the ownership of inventions, trade secrets, know-how and other intellectual property resulting from the joint

creation or use of intellectual property by our licensors and us and our collaborators;

–the priority of invention of patented technology; and

–the amounts to be paid pursuant to certain program milestones being achieved or to royalty obligations,

including the triggering of royalty obligations and amounts to be paid pursuant thereto.

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If disputes over intellectual property that we have in-licensed or other related contractual rights prevent or impair

our ability to maintain our current licensing arrangements on favorable terms, we may be unable to successfully

develop and commercialize the affected product candidates.

We are generally also subject to all of the same risks with respect to protection of intellectual property that we

license, as we are for intellectual property that we own, which are described below. If we, our co-owners or our

licensors fail to adequately protect, defend, maintain or enforce this intellectual property, our ability to

commercialize products could suffer.

We and our collaborators rely on third parties to manufacture certain of our clinical product supplies,

and we may have to rely on third parties to produce and process our product candidates, if approved.

Although we expect to continue using our own clinical manufacturing facilities where available, we also rely on

outside vendors to manufacture supplies and process our product candidates. We only manufacture our

COVID-19 vaccine on a commercial scale and may not be able to achieve commercial-scale manufacturing and

processing for our other product candidates, if approved, and may be unable to create an inventory of mass-

produced, off-the-shelf product to satisfy demands for our product candidates, if approved.

We do not yet have sufficient information to reliably estimate the cost of the commercial manufacturing and

processing of our product candidates, and the actual cost to manufacture and process our product candidates

could materially and adversely affect the commercial viability of our product candidates. As a result, we may not

be able to develop commercially viable products other than our COVID-19 vaccine.

In addition, our reliance on a limited number of CMOs exposes us to the following risks:

–we may be unable to identify manufacturers on acceptable terms or at all because the number of potential

manufacturers is limited and the FDA or other regulatory authorities may have questions regarding any

replacement contractor. This may require new testing and regulatory interactions. In addition, a new

manufacturer would have to be educated in, or develop substantially equivalent processes for, production of

our products after receipt of regulatory authority questions, if any;

–our CMOs might be unable to timely formulate and manufacture our product or produce the quantity and

quality required to meet our clinical and commercial needs, if any;

–CMOs may not be able to execute our manufacturing procedures appropriately;

–our future CMOs may not perform as agreed or may not remain in the contract manufacturing business for the

time required to supply our clinical trials or to successfully produce, store and distribute our products;

–manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the U.S. Drug

Enforcement Administration and corresponding state agencies and by regulatory authorities in other

jurisdictions to ensure strict compliance with GMP and other government regulations and corresponding

standards in other jurisdictions. We do not have control over CMOs’ compliance with these regulations and

standards;

–we may not own, or may have to share, the intellectual property rights to any improvements made in the

manufacturing process for our products;

–our CMOs could breach or terminate their agreement with us; and

–our CMOs would also be subject to the same risks we face in developing our own manufacturing capabilities,

as described above.

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Each of these risks could delay our clinical trials, the approval, if any, of our COVID-19 vaccine or product

candidates by the FDA or regulatory authorities in other jurisdictions or the commercialization of our COVID-19

vaccine or product candidates, or result in higher costs or deprive us of potential product sales revenue. In

addition, we will rely on third parties to perform release tests on our COVID-19 or our product 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.

We and certain of our collaborators currently rely on CMOs located outside of the United States to manufacture

clinical materials. Such ex-U.S. CMOs may be subject to or affected by U.S. legislation, executive orders,

regulations, or investigations, including but not limited to the recently enacted BIOSECURE Act, the Department

of Justice’s Final Rule issued on January 8, 2025 implementing the Executive Order on Preventing Access to

Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern,

sanctions, trade restrictions and other U.S. and other regulatory requirements, which could increase the cost or

reduce the supply of material available to us, delay or restrict the procurement or supply of such material, delay

or impact clinical trials, have an adverse effect on our ability to secure significant commitments from

governments to purchase our potential therapies and adversely affect our financial condition and business

prospects.

We are dependent on single source suppliers for some of the components and materials used in, and the

processes required to develop, our COVID-19 vaccine and our product candidates.

We currently depend on single source suppliers for some of the components and materials used in, and

manufacturing processes required to develop, our COVID-19 vaccine and our product candidates. We cannot

ensure that these suppliers or service providers will remain in business, or have sufficient capacity or supply to

meet our needs, or that they will not be purchased by one of our competitors or another company that is not

interested in continuing to work with us. Our use of single source suppliers of raw materials, components, key

processes and finished goods exposes us to several risks, including disruptions in supply, price increases or late

deliveries. There are, in general, relatively few alternative sources of supply for substitute components. These

vendors may be unable or unwilling to meet our future demands for our clinical trials or commercial sale.

Establishing additional or replacement suppliers for these components, materials and processes could take a

substantial amount of time and it may be difficult to establish replacement suppliers who meet regulatory

requirements. Any disruption in supply from any single source supplier or service provider could lead to supply

delays or interruptions which would damage our business, financial condition, results of operations and

prospects.

If we have to switch to a replacement supplier, the manufacture and delivery of our product candidates could be

interrupted for an extended period, which could adversely affect our business. Establishing additional or

replacement suppliers for any of the components or processes used in our COVID-19 vaccine and our product

candidates, if required, may not be accomplished quickly. If we are able to find a replacement supplier, the

replacement supplier would need to be qualified and may require additional regulatory authority approval, which

could result in further delay. While we seek to maintain adequate inventory of the single source components and

materials used in our COVID-19 vaccine and our product candidates, any interruption or delay in the supply of

components or materials, or our inability to obtain components or materials from alternate sources at acceptable

prices in a timely manner, could impair our ability to meet the demand for our COVID-19 vaccine and product

candidates.

In addition, as part of the FDA’s approval of our product candidates, we will also require FDA review of the

individual components of our process, which include the manufacturing processes and facilities of our single

source suppliers.

Our reliance on these suppliers, service providers and manufacturers subjects us to a number of risks that could

harm our reputation, business and financial condition, including, among other things:

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–delays to the development timelines for our product candidates;

–interruption of supply resulting from modifications to or discontinuation of a supplier’s operations;

–delays in product shipments resulting from uncorrected defects, reliability issues, or a supplier’s variation in a

component;

–a lack of long-term supply arrangements for key components with our suppliers;

–inability to obtain adequate supply in a timely manner, or to obtain adequate supply on commercially

reasonable terms;

–difficulty and cost associated with locating and qualifying alternative suppliers for our components in a timely

manner;

–production delays related to the evaluation and testing of components from alternative suppliers, and

corresponding regulatory qualifications;

–delay in delivery due to our suppliers’ prioritizing other customer orders over ours;

–damage to our reputation caused by defective components produced by our suppliers; and

–fluctuation in delivery by our suppliers due to changes in demand from us or their other customers.

If any of these risks materialize, costs could significantly increase and our ability to meet demand for our

products could be impacted.

Risks Related to Intellectual Property

If our efforts to obtain, maintain, protect, defend and/or enforce the intellectual property related to our

COVID-19 vaccine or our product candidates and technologies are not adequate, we may not be able to

compete effectively in our market.

Our commercial success depends in part on our ability to obtain, maintain, protect, defend and enforce patent

and other intellectual property, including trade secret and know-how, protection for our COVID-19 vaccine and

for our product candidates, proprietary technologies and their uses, as well as our ability to operate, develop,

manufacture and commercialize our COVID-19 vaccine or one or more of our product candidates without

infringing, misappropriating or otherwise violating the intellectual property or other proprietary rights of our

competitors or any other third parties, including any non-practicing entities or patent assertion entities. We

generally seek to protect our intellectual property position by filing and/or licensing patent applications in the

European Union, the United States and elsewhere related to our product candidates, proprietary technologies

(including methods of manufacture) and their uses that are important to our business. Our patent applications

cannot be enforced against third parties practicing the technology claimed in such applications unless, and until,

patents issue from such applications, and then only to the extent that the issued claims cover third parties’

activities in the countries in which they are performed. We cannot be certain that the claims in any of our patent

applications will be considered patentable by the United States Patent and Trademark Office, or the USPTO,

courts in the United States or the patent offices and courts in other jurisdictions, including Europe, nor can we be

certain that any claim in our issued patents will not be found invalid or unenforceable if challenged. Accordingly,

there can be no assurance that our patent applications or those of our licensors will result in additional patents

being issued or that issued patents will adequately cover our COVID-19 vaccine or our product candidates, or

otherwise afford sufficient protection against competitors with similar technology, nor can there be any assurance

that issued patents will not be infringed, designed around, invalidated or held unenforceable. Furthermore, we

may not be able to apply for patents on certain aspects of our current or future products or product candidates,

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proprietary technologies and their uses in a timely fashion, at a reasonable cost, in all jurisdictions, or at all, and

any potential patent protection we obtain may not be sufficient to prevent substantial competition.

Even claims of issued patents may later be found invalid or unenforceable, or may be modified or revoked in

proceedings before various patent offices or in courts in the United States, Europe or other jurisdictions. The

degree of future protection for our intellectual property and other proprietary rights is uncertain. Only limited

protection may be available and may not adequately protect our rights or permit us to gain or keep any

competitive advantage. If we do not adequately obtain, maintain, protect, defend and enforce our intellectual

property and proprietary technology, competitors may be able to use our products, product candidates and

proprietary technologies and erode or negate any competitive advantage we may have, which could have a

material adverse effect on our financial condition and results of operations.

The patent application process is subject to numerous risks and uncertainties, and there can be no assurance

that we or any of our current or future licensors or collaborators will be successful in prosecuting, obtaining,

protecting, maintaining, enforcing or defending patents and patent applications necessary or useful to protect our

products or product candidates, proprietary technologies (including methods of manufacture) and their uses.

These risks and uncertainties include, from time to time, the following:

–the USPTO and various other governmental patent agencies require compliance with a number of procedural,

documentary, fee payment and other provisions during the patenting process, the noncompliance with which

can result in abandonment or lapse of a patent or patent application or a finding that a patent is

unenforceable, and partial or complete loss of patent rights in the relevant jurisdiction;

–patent applications may not result in any patents being issued;

–claims of issued patents that we own (solely or jointly) or have in-licensed may be challenged, invalidated,

modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive

advantage;

–other parties may have designed around our patent claims or developed technologies that may be related or

competitive to our COVID-19 vaccine or to our product candidates or other technologies, may have filed or

may file patent applications and may have received or may receive patents that overlap or conflict with our

patent filings, either by claiming the same or overlapping methods, products, reagents, tools or devices or by

claiming subject matter that could dominate one or more of our patent claims;

–any successful opposition to claims of any patents owned by or in-licensed to us could deprive us of rights

necessary for the development and exploitation of our COVID-19 vaccine or our product candidates and other

technologies, or the successful commercialization of any product candidates and other technologies that we

may develop;

–because patent applications in the United States and most other jurisdictions are confidential for a period of

time after filing, we cannot be certain that we, our co-owners or our licensors were the first to file any patent

application related to our product candidates, proprietary technologies and their uses;

–a court or patent office proceeding, such as a derivative action or interference, can be provoked or instituted

by a third party or a patent office, and might determine that one or more of the inventions described in our

patent filings, or in those we licensed, was first invented by someone else, so that we may lose rights to such

invention(s);

–a court or other patent proceeding, such as an inter partes review, post grant review or opposition, can be

instituted by a third party to challenge the inventorship, scope, validity and/or enforceability of our patent

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claims and might result in invalidation or revision of one or more of our patent claims, or in a determination

that such claims are unenforceable;

–there may be significant pressure on the U.S. government and international governmental bodies to limit the

scope of patent protection both inside and outside the United States for disease treatments that prove

successful, as a matter of public policy regarding worldwide health concerns; existing legislation (for example,

in the United States, the Public Readiness and Emergency Preparedness Act, etc.) may be interpreted, and

new legislation may be passed, to permit third-party use of patented technologies relating to a public health

concern, with little or no compensation to the patent holder(s); and

–countries other than the United States may have patent laws less favorable to patentees than those upheld by

U.S. courts, allowing competitors a better opportunity to create, develop and market competing product

candidates.

The patent position of biopharmaceutical companies generally is highly uncertain, involves complex legal and

factual questions, and has been the subject of much litigation in recent years. The standards that the USPTO

and its counterparts use to grant patents are not always applied predictably or uniformly and can change.

Similarly, the ultimate degree of protection that will be afforded to biotechnology inventions, including ours, in the

United States and other countries, remains uncertain and is dependent upon the scope of the protection decided

upon by patent offices, courts and lawmakers. Moreover, there are periodic changes in patent law, as well as

discussions in the U.S. Congress and in other jurisdictions about modifying various aspects of patent law. There

is no uniform, worldwide policy regarding the subject matter and scope of claims granted or allowable in

pharmaceutical or biotechnology patents. In certain countries, for example, methods for the medical treatment of

humans are not patentable. More generally, the laws of some countries do not protect intellectual property rights

to the same extent as U.S. or EU laws, and those countries may lack adequate rules and procedures for

granting, maintaining, protecting, defending and enforcing our intellectual property rights.

Furthermore, the patent prosecution process is expensive and time-consuming, and we may not be able to file,

prosecute, maintain, protect, defend, enforce or license all necessary or desirable patents or patent applications,

as applicable, at a reasonable cost or in a timely manner. It is possible that we will fail to identify patentable

aspects of our research and development output in time to obtain patent protection. Although we enter into non-

disclosure and confidentiality agreements with parties who have access to confidential or patentable aspects of

our research and development output, such as our employees, corporate collaborators, outside scientific

collaborators, CROs, CMOs, consultants, advisors and other third parties, if any of these parties were to breach

such agreements and improperly disclose such output before a patent application is filed, this could jeopardize

our ability to seek patent protection. We also rely to a certain extent on trade secrets, know-how, and technology,

which are not protected by patents, to maintain our competitive position. If any trade secret, know-how or other

technology not protected by a patent were to be disclosed to or independently developed by a competitor, our

business and financial condition could be materially adversely affected.

The issuance of a patent is not conclusive as to its inventorship, priority date, scope, term, validity or

enforceability so that any patents that may issue or that we may license may be challenged in the courts or

patent offices in the United States, Europe and other jurisdictions. Once granted, patents may remain open to a

variety of challenges, including opposition, interference, re-examination, post-grant review, inter partes review,

nullification or derivation action in court or before patent offices or similar proceedings, and furthermore, may be

challenged as a defense in any enforcement action that we might bring. Such challenges may result in loss of

exclusivity or in patent claims being narrowed, terminated, disclaimed, invalidated, assigned to others or held

unenforceable, any or all of which could limit our ability to stop others from using or commercializing similar or

identical products, or limit the scope and/or term of patent protection of our products and product candidates

and/ or eliminate it altogether, thus hindering or removing our ability to limit third parties from making, using or

selling products or technologies that are similar or identical to ours, and/or reduce or eliminate royalty payments

to us from our licensees. Given the amount of time required for the development, testing and regulatory review of

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new product candidates, patents protecting such candidates might expire before or shortly after such candidates

are commercialized. Furthermore, our pending and future patent applications may not result in patents being

issued which protect our technology or our product(s) or product candidates, or which effectively prevent others

from commercializing competitive technologies and products. As a result, our intellectual property may not

provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

Our ability to enforce our owned and in-licensed patent and other intellectual property rights depends on our

ability to detect infringement, misappropriation and other violation of such patents and other intellectual property.

It may be difficult to detect infringers, misappropriators and other violators who do not advertise the components

or methods that are used in connection with their products and services. Moreover, it may be difficult or

impossible to obtain evidence of infringement, misappropriation or other violation in a competitor’s or potential

competitor’s product or service, and in some cases we may not be able to introduce obtained evidence into a

proceeding or otherwise utilize it to successfully demonstrate infringement. We may not prevail in any lawsuits

that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially

meaningful.

Furthermore, patents or other intellectual property rights that we may be able to secure for our COVID-19

vaccine or our other COVID-19 vaccine candidates could be restricted or preempted if governments determine

that they will not enforce, or will require compulsory licensing of, technologies useful to address the spread of

COVID-19.

In addition, proceedings to enforce or defend our owned or in-licensed patents could put our patents at risk of

being invalidated, held unenforceable or interpreted narrowly. Such proceedings could also provoke third parties

to assert claims against us, including that some or all of the claims in one or more of our patents are invalid or

otherwise unenforceable. Such challenges may result in loss of patent rights, loss of exclusivity, or in patent

claims being narrowed, invalidated or held unenforceable, which could limit our ability to stop others from using

or commercializing similar or identical technology and products, or limit the duration of the patent protection of

our technology and product candidates. If any of our owned or in-licensed patents covering our product

candidates or other technologies are narrowed, invalidated or found unenforceable, or if a court found that valid,

enforceable patents held by third parties covered one or more of our product candidates or other technologies,

our competitive position could be harmed or we could be required to incur significant expenses to protect,

enforce or defend our rights. If we initiate lawsuits to protect, defend or enforce our patents, or litigate against

third-party claims, such proceedings would be expensive and would divert the attention of our management,

technical personnel, and other employees even if the eventual outcome is favorable to us.

The degree of future protection for our intellectual property and other proprietary rights is uncertain, and we

cannot ensure that:

–any of our patents, or any of our pending patent applications, if issued, or those of our licensors, will include

claims having a scope sufficient to protect our product(s), our product candidates and other technologies;

–any of our pending patent applications or those of our licensors may issue as patents;

–others will not or may not be able to make, use, offer to sell or sell products that are the same as or similar to

our own but that are not covered by the claims of the patents that we own or license;

–we will be able to successfully commercialize our products on a substantial scale, if approved, before the

relevant patents that we own or license expire;

–we were the first to make the inventions covered by each of the patents and pending patent applications that

we own or license;

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–we, our co-owners or our licensors were the first to file patent applications for these inventions;

–others will not develop similar or alternative products or technologies that do not infringe the patents we own

or license;

–any of the claims of patents we own or license will be found to ultimately be valid and enforceable;

–any patents issued to us or our licensors will provide a basis for an exclusive market for our commercially

viable product candidates and other technologies or will provide us with any competitive advantages;

–a third party may not challenge the claims of patents we own or license and, if challenged, a court would hold

that such patent claims are valid, enforceable and infringed;

–we may develop or in-license additional proprietary technologies that are patentable;

–the patents of others will not have an adverse effect on our ability to issue patents, or otherwise on our

business;

–our competitors do not conduct research, development, testing or commercialization activities in countries

where we do not have enforceable patent rights and then use the information learned from such activities to

develop competitive products for sale in our major commercial markets;

–we will develop additional proprietary technologies, product(s) or product candidates that are separately

patentable; and

–our, or our collaborators’, development and commercialization activities, including our manufacturing

processes, or products will not infringe patents of our competitors or any other third parties, including any non-

practicing entities or patent assertion entities.

Other companies or organizations may challenge our intellectual property rights or the intellectual

property rights of our partners or may assert intellectual property rights that prevent us or our partners

from developing and commercializing our COVID-19 vaccine or our product candidates and other

technologies.

We practice in new and evolving scientific fields, the continued development and potential use of which has

resulted in many different patents and patent applications from organizations and individuals seeking to obtain

intellectual property protection in the fields. We own and in-license patent applications and issued patents that

describe and/or claim certain technologies, including products, reagents, formulations, tools and methods

including uses and manufacturing methods, or features or aspects of any of these. These issued patents and

pending patent applications claim certain compositions of matter and methods relating to the discovery,

development, testing, manufacture and commercialization of therapeutic modalities and our delivery

technologies, including lipid nanoparticles, or LNPs. If we, our co-owners or our licensors are unable to obtain,

maintain, protect, defend or enforce patent protection with respect to our products, product candidates and other

technology and any other products, product candidates and technology that we may develop, our business,

financial condition, results of operations and prospects could be materially harmed.

As the scientific fields mature, our known competitors and other third parties, many of whom have substantially

greater resources than we do and many of whom have made significant investments in competing technologies,

may seek or may have already obtained patents, and they have filed and will continue to file patent applications

claiming inventions in the fields in the United States and elsewhere. This may limit, interfere with or eliminate our

and our partners’ ability to make, use, sell, import or otherwise exploit our COVID-19 vaccine or our product

candidates or other technologies. There is uncertainty about which patents will issue, and, if they do, as to when,

to whom and with what claims. With respect to both in-licensed and owned intellectual property, we cannot

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predict whether the patent applications we and our licensors are currently pursuing will issue as patents in any

particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from

competitors.

We, our co-owners, our partners or our licensors may in the future become a party to patent proceedings or

priority disputes in the United States, Europe or other jurisdictions. In the United States, the Leahy-Smith

America Invents Act, or the America Invents Act, includes a number of significant changes that affect the way

patent applications are prosecuted and also may affect patent litigation. These include allowing third-party

submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of

a patent through USPTO-administered post-grant proceedings, including post-grant review, inter partes review

and derivation proceedings. We expect that our competitors and other third parties will institute litigation and

other proceedings, such as interference, reexamination and opposition proceedings, as well as inter partes and

post-grant review proceedings against us and the patents and patent applications that we own and in-license.

Additionally, we face ongoing COVID-19 vaccine-related patent litigation. We filed a nullity action in the Federal

Patent Court of Germany seeking a declaration that EP1857122B1, or EP’122, is invalid, initiated cancellation

actions against the CureVac IP in the German Patent and Trademark Office, and filed opposition proceedings in

the European Patent Office, or EPO, seeking the revocation of EP3708668B1, or EP’668, and EP4023755B1, or

EP’755. ModernaTX, Inc., or Moderna, has brought litigation against us and Pfizer regarding European patents

3590949B1, or EP’949, and 3718565B1, or EP’565, in Germany, England and Wales (only EP’949 currently at

issue), the Netherlands, Ireland, and Belgium, and regarding U.S. Patent Nos. 10,898,574, 10,702,600, and

10,933,127 in the United States. BioNTech and Pfizer also initiated proceedings seeking the revocation of

EP’949 in the Business and Property Courts of England and Wales and have filed opposition proceedings in the

EPO seeking the revocation of EP’949 and EP’565. BioNTech and Pfizer have filed petitions for inter partes

review before the Patent Trial and Appeal Board in the United States with respect to U.S. Patent Nos.

10,702,600 and 10,933,127. Arbutus Biopharma Corp., or Arbutus, and Genevant Sciences GmbH, or Genevant,

have brought litigation against us and Pfizer in the United States regarding U.S. Patent Nos. 9,504,651,

8,492,359, 11,141,378, 11,298,320, and 11,318,098. Promosome LLC, or Promosome, has initiated litigation

against us and Pfizer in the Unified Patent Court (Munich Division) regarding one European patent, EP 2 401

365. GlaxoSmithKline Biologicals SA and GlaxoSmithKline LLC, or collectively, GSK, have brought litigation

against us and Pfizer in the United States regarding U.S. Patent Nos. 11,638,693, 11,638,694, 11,666,534,

11,766,401, 11,786,467, 11,759,422, 11,655,475, and 11,851,660, and in the High Court of Ireland, as well as the

United Patent Court, regarding European Patent Nos. 2,590,626, 4,066,856, and 4,226,941. BioNTech and

Pfizer also initiated proceedings seeking the revocation of EP’626, EP’856, and EP’941 in the Business and

Property Courts of England and Wales and have filed opposition proceedings in the EPO seeking the revocation

of EP’856 and EP’941. Bayer CropScience LLC, or Bayer, Monsanto Company, and Monsanto Technology, LLC,

or Monsanto, have initiated litigation against us and Pfizer in the United States District Court for the District of

Delaware regarding one U.S. Patent No. 7,741,118. We cannot guarantee that we will not become subject to

additional COVID-19 vaccine patent infringement lawsuits in the future. In addition, should Pfizer not prevail in

any of the ongoing COVID-19 vaccine patent infringement lawsuits to which it is a party, Pfizer may seek to

require us to indemnify Pfizer for losses suffered therefrom as well as any losses from future COVID-19 vaccine

patent infringement lawsuits in which it does not prevail. We believe we have strong defenses against each of

these claims and intend to vigorously defend ourselves in each proceeding, but we can make no assurances

regarding the ultimate outcome of any of these matters. Additionally, as we continually evaluate these various

proceedings, we may from time to time make strategic decisions to settle or otherwise resolve certain

proceedings despite our continued belief in the strengths of our defenses.

We expect that we will continue to be subject to similar proceedings or priority disputes, including oppositions, in

Europe or other jurisdictions relating to patents and patent applications in our portfolio.

If we, our co-owners, our partners or our licensors are unsuccessful in any interference proceedings or other

priority or validity disputes, including any derivations, post-grant review, inter partes review or oppositions, to

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which we or they are subject, we may lose valuable intellectual property rights through the narrowing or loss of

one or more patents owned or in-licensed, or our owned or in-licensed patent claims may be narrowed,

invalidated or held unenforceable. In many cases, the possibility of appeal exists for either us or our opponents,

and it may be years before final, unappealable rulings are made with respect to these patents in certain

jurisdictions. The timing and outcome of these and other proceedings is uncertain and may adversely affect our

business if we are not successful in defending the patentability and scope of our pending and issued patent

claims. Even if our rights are not directly challenged, disputes could lead to the weakening of our intellectual

property rights. Our defense against any attempt by third parties to circumvent or invalidate our intellectual

property rights could be costly to us, could require significant time and attention of our management, technical

personnel and other employees and could have a material adverse impact on our business and our ability to

successfully compete against our current and future competitors.

There are many issued and pending patent filings that claim aspects of technologies that we may need for our

mRNA products or product candidates, or other product candidates, including patent filings that relate to relevant

delivery technologies. There are also many issued patents that claim targeting genes or portions of genes that

may be relevant for immunotherapies we wish to develop. In addition, as evidenced by the lawsuits brought

against Moderna, Pfizer and us, there may be additional issued and pending patent applications that may be

asserted against us in a court proceeding or otherwise based upon the asserting party’s belief that we may need

such patents for the development, manufacturing, testing and commercialization of our COVID-19 vaccine or of

our product candidates. Thus, it is possible that one or more organizations, ranging from our competitors to non-

practicing entities or patent assertion entities, has or will hold patent rights to which we may need a license, or

hold patent rights which could be asserted against us. Such licenses may not be available on commercially

reasonable terms or at all, or may be non-exclusive. If those organizations refuse to grant us a license to such

patent rights on reasonable terms, if we fail to invalidate relevant patents, or if a court or other governing body

determines that we need such patent rights that have been asserted against us and we are not able to obtain a

license on reasonable terms or at all, we may be unable to perform research and development or other activities

or market products covered by such patents, and we may need to cease the development, manufacture, testing

and commercialization of one or more of the product candidates we may develop. Any of the foregoing could

result in a material adverse effect on our business, financial condition, results of operations or prospects.

We may not be successful in obtaining, maintaining, protecting or defending the necessary intellectual

property rights to allow us to identify and develop product candidates, and test product components and

manufacturing processes for our development pipeline.

We currently have rights to certain intellectual property through our owned and in-licensed patents and other

intellectual property rights relating to identification, development and testing of our product candidates or other

technologies. As our activities may involve additional product candidates or services that could require the use of

intellectual property and other proprietary rights held by third parties, the growth of our business could depend in

part on our ability to acquire, in-license or use such intellectual property and proprietary rights. In addition, our

product candidates may require specific formulations to work effectively and efficiently and these intellectual

property and other proprietary rights may be held by others. We may be unable to secure such licenses or

otherwise acquire or in-license any compositions, methods of use, processes or other third-party intellectual

property rights from third parties that we identify as necessary, on reasonable terms, or at all, for product

candidates and other technologies that we may develop. The licensing and acquisition of third-party intellectual

property rights is a competitive area, and a number of more established companies are also pursuing strategies

to license or acquire third-party intellectual property rights that we may consider attractive or necessary. These

established companies may have a competitive advantage over us due to their size, cash resources, and greater

clinical development and commercialization capabilities.

We sometimes collaborate with academic institutions and/or utilize services of CROs and CMOs in certain

aspects of our research or development under written agreements with these parties. These agreements may

not ensure protection of intellectual property rights in developed technology, or may fail to provide us with

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sufficient control of or access to such intellectual property rights. For example, agreements with these academic

institutions typically provide us with an option to negotiate a license to any of the institution’s rights in technology

resulting from the collaboration. However, these institutions may not honor our option and right of first negotiation

for intellectual property rights or we may otherwise be unable to negotiate a license within the specified time

frame or under terms that are acceptable to us. If we are unable to do so, the institution may offer the intellectual

property rights to other parties, potentially blocking our ability to pursue our program or otherwise continue to

develop certain product candidates or other technologies. CROs and/or CMOs may control certain technologies

that were utilized in and/or developed through work on our behalf, and may not pursue protection of such

technologies, or may provide us with only non-exclusive rights in such technologies, so that relevant

technologies may be shared with other parties including our competitors. In any relationship with a third party,

there is a risk of disagreement over intellectual property rights (including inventorship or ownership of, rights to

protect and/or enforce, and/or rights to use) in utilized or developed technologies.

Moreover, some of our owned patents and patent applications are, and may in the future be, co-owned with third

parties. If we are unable to obtain, or continue to maintain, exclusive rights to any such third-party co-owners’

interest in such patents or patent applications, such co-owners may be able to license their rights to other third

parties, including our competitors, and our competitors could market competing products and technologies. In

addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents

against third parties, and such cooperation may not be provided to us. Any of the foregoing could have a material

adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

In addition, third parties that perceive us to be a competitor may be unwilling to assign or license rights to us. We

also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to

make an appropriate return on our investment. If we are unable to successfully obtain rights to required third-

party intellectual property rights or maintain, protect, defend or enforce the existing intellectual property rights we

have, we may have to abandon the development and commercialization of the relevant program or product

candidate, which could have a material adverse effect on our business, financial condition, results of operations

and prospects.

The lifespans of our patents may not be sufficient to effectively protect our products or product

candidates, technologies and business.

Patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after

its first effective non-provisional filing date, assuming maintenance fees are timely paid after the patent has

issued. Most other jurisdictions also provide a 20-year nominal patent term, though many require payment of

regular, often annual, annuities to maintain pendency of an application or viability of an issued patent. In some

jurisdictions, one or more options for extension of a patent term may be available, but even with such

extensions, the lifespan of a patent, and the protection it affords, is limited. Even if patents covering our product

candidates, proprietary technologies and their uses are obtained, once the patent term has expired, we may be

subject to competition from third parties that can then use the inventions included in such patents to create

competing products and technologies. In addition, although upon issuance in the United States a patent’s life

can be increased based on certain delays caused by the USPTO, this increase can be reduced or eliminated

based on certain delays caused by the patent applicant during patent prosecution. The USPTO can also require,

in certain circumstances, that the expiration date of a subject patent be shortened by the filing of a terminal

disclaimer over one or more patents that may expire sooner than the subject patent. Given the amount of time

required for the development, testing and regulatory review of new product candidates, patents protecting such

product candidates might expire before or shortly after such candidates are commercialized. If any patents that

we own or in-license expire, we would not be able to stop others from using or commercializing similar or

identical technology and products, and our competitors could market competing products and technology. Any of

the foregoing could have a material adverse effect on our competitive position, business, financial conditions,

results of operations and prospects.

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If we do not obtain patent term extension and data exclusivity for any product candidates we may

develop, our business may be materially harmed.

Depending upon the timing, duration and specifics of any FDA marketing approval of any product candidates we

may develop, one or more of our U.S. patents 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 for a drug product subject to the provisions of the Hatch-Waxman Act.

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 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. For example, we did not extend any patent for our COVID-19 vaccine.

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

competitors may obtain approval of competing products following our patent expiration, and our business,

financial condition, results of operations and prospects could be materially harmed.

If we fail to comply, or are viewed to have failed to comply, with our obligations in the agreements under

which we license intellectual property rights from third parties or otherwise experience disruptions to

our business relationships with our licensors or other third parties, we could lose license rights that are

important to our business or suffer monetary losses.

We are heavily reliant upon licenses to certain intellectual property and other proprietary rights from third parties

that are important or necessary to the development and commercialization of our technology and product(s) or

product candidates, and we expect to enter into similar license agreements in the future. Licensing of intellectual

property is important to our business and involves complex legal, business and scientific issues and is

complicated by the rapid pace of scientific discovery in our industry. Our licenses may not provide exclusive

rights to use such intellectual property and technology in all relevant fields of use and in all territories in which we

may wish to develop, test, or commercialize our technology and products in the future. As a result, we may not

be able to prevent competitors from developing and commercializing competitive products in territories included

in any or all of our licenses.

Where we obtain licenses from, or collaborate with, third parties, in some circumstances we may not have the

right to control the preparation, filing, prosecution, maintenance, enforcement and defense of patents and patent

applications covering the technology that we license from, or that arises through collaboration with, such third

parties, or such activities, if controlled by us, may require the input of such third parties. In some cases, patent

prosecution (including preparation and filing) of our in-licensed intellectual property or of intellectual property

developed through collaboration, is controlled solely by the licensor or collaborator. We may also require the

agreement and/or cooperation of our licensors and collaborators to protect, enforce, utilize, or defend any in-

licensed patent rights, and such agreement and/or cooperation may not be provided. Therefore, we cannot be

certain that these patents and patent applications will be prepared, filed, prosecuted, maintained, protected,

enforced or defended in a manner consistent with the best interests of our business. Any patents or patent

applications that we in-license may be challenged, narrowed, circumvented, invalidated or held unenforceable,

or our licensors may not properly maintain such patents or patent applications and they may expire. If our

licensors fail to obtain, maintain, defend, protect or enforce the intellectual property we license from them, we

could lose our rights to the intellectual property and our competitors could market competing products using the

inventions in such intellectual property. In certain cases, we control the prosecution of patents included from in-

licensed technology. In the event we breach any of our obligations related to such prosecution, we may incur

significant liability to our collaborators. If we and our licensors or collaborators disagree over IP protection

strategies for relevant technologies, disputes may arise, and we could lose access to or control over protection

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of technologies important to our business. If so, we may not be able to adequately protect our product(s) or

product candidates, including not being able to prevent a competitor or other third party from developing the

same product(s) or product candidates for the same or a different use. Any of the foregoing could have a

material adverse effect on our competitive position, business, financial conditions, results of operations and

prospects.

Moreover, we may disagree from time to time with licensors or collaborators regarding, among other things, the

interpretation of each party’s obligations or the amounts payable under our agreements. For example, we were

in discussions with the University of Pennsylvania, or UPenn, and the National Institutes of Health, or the NIH,

concerning royalties and other related amounts allegedly owed on sales of our COVID-19 vaccine since

commercialization. UPenn subsequently filed suit against us in the U.S. District Court for the Eastern District of

Pennsylvania in connection with this dispute. On December 20, 2024, we entered into a Settlement Agreement

with the NIH pursuant to which we agreed, among other things, to pay $791.5 million to the NIH. On March 27,

2025, we entered into a Settlement Agreement with UPenn pursuant to which we agreed, among other things, to

pay up to $467.0 million to UPenn, consisting of $400.0 million as royalties for calendar years 2020-2023, up to

$15.0 million in funding for a three-year extension of the research term of our and UPenn’s vaccine alliance, and

$52.0 million as a contribution to a research and development investment fund to be jointly managed by us and

UPenn. For more information regarding our settlements with the NIH and UPenn, see Note 12.2 of our

consolidated financial statements included elsewhere in this Annual Report.

If we are found to have failed to satisfy obligations or materially breached any of our agreements, such as

licenses to third-party intellectual or any disagreements between us and our licensors, a licensor could

potentially have the right or reason to terminate the license or to exercise the option of a non-exclusive license,

which would allow our competitors to have access to the same intellectual property and technology licensed to

us. Our existing license agreements impose, and we expect that future license agreements will impose, various

diligence, milestone and royalty payment, exclusivity and other obligations on us. If we fail to comply with our

obligations under these agreements, including royalty payments, or we are subject to a bankruptcy, the licensor

may have the right to terminate the license agreement, in which event we would not be able to develop, market

and commercialize product(s) or product candidates covered by the license agreement. In spite of our best

efforts and even if we disagree, our licensors might still conclude that we have materially breached our license

agreements and might therefore terminate the license agreements, thereby removing our ability to develop, test

and commercialize the product(s) or product candidates covered by these license agreements. In the event that

any of our license agreements were to be terminated by the licensor, we may need to negotiate new or

reinstated agreements, which may not be available to us on equally favorable terms, or at all. If these license

agreements are rightfully terminated, or if the underlying patents or other intellectual property fail to provide the

intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market and

commercialize, products similar or identical to ours, and our licensors may be able to seek additional judicial

remedies. In addition, we may seek to obtain additional licenses from our licensors and, in connection with

obtaining such licenses, we may agree to amend our existing license agreements in a manner that may be more

favorable to the licensors, including by agreeing to terms that could enable third parties (potentially including our

competitors) to receive licenses to a portion of the intellectual property that is subject to our existing licenses.

Failure to prevail with respect to any contractual disagreements could result in a material adverse effect on our

competitive position, business, financial conditions, results of operations or prospects, particularly if discussions

result in legal or other dispute resolution proceedings.

We are generally also subject to all of the same risks with respect to protection of intellectual property that we

license, as we are for intellectual property that we own, which are described in this section. If we, our co-owners

or our licensors fail to adequately protect this intellectual property, our ability to develop, test, market and

commercialize our product(s) or product candidates could suffer. Moreover, if disputes over intellectual property

that we have in-licensed prevent or impair our ability to maintain our current licensing arrangements on

commercially acceptable terms, we may be unable to successfully develop, test, market and commercialize the

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affected product(s) or product candidates, which could have a material adverse effect on our business, financial

condition, results of operations and prospects.

Some of our in-licensed intellectual property has been discovered through government-funded

programs and thus may be subject to federal regulations such as “march-in” rights and certain reporting

requirements, and compliance with such regulations may limit our exclusive rights and our ability to

contract with manufacturers.

Certain intellectual property rights that have been in-licensed, including patent applications and patents that we

in-license from the University of Pennsylvania, the Louisiana State University, the Broad Institute, the NIH,

Genevant, and CellScript, have been generated through the use of U.S. government funding and are therefore

subject to certain federal regulations. The U.S. government may have certain rights to intellectual property

embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980, or the Bayh-Dole

Act. These U.S. government rights may include a non-exclusive, non-transferable, irrevocable worldwide license

to use inventions covered by that Act for any governmental purpose. In addition, the U.S. government may have

the right, under certain limited circumstances, to require the licensor to grant exclusive, partially exclusive or

non-exclusive licenses to any of these inventions to a third party if it determines that (i) adequate steps have not

been taken to commercialize the invention, (ii) government action is necessary to meet public health or safety

needs or (iii) government action is necessary to meet requirements for public use under federal regulations (also

collectively referred to as “march-in rights”). The U.S. government may also have the right to take title to these

inventions if the licensor fails to disclose the invention to the government or fails to file an application to register

the intellectual property within specified time limits. Any exercise by the government of such rights could harm

our competitive position, business, financial condition, results of operations and prospects. Intellectual property

generated under a government-funded program is also subject to certain reporting requirements, compliance

with which may require us to expend substantial resources.

In addition, the U.S. government requires that any products embodying any such inventions or produced through

the use of any such inventions be manufactured substantially in the United States. This preference for U.S.

industry may be waived by the federal agency that provided the funding if the owner or assignee of the

intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on

similar terms to potential licensees that would be likely to manufacture the products substantially in the United

States or that under the circumstances domestic manufacture is not commercially feasible. We may not be able

to obtain a waiver of this preference for U.S. industry, and this preference may limit our ability to contract with

non-U.S. product manufacturers for products covered by such intellectual property. To the extent any of our

owned or in-licensed future intellectual property is generated through the use of U.S. government funding, the

provisions of the Bayh-Dole Act may similarly apply. If we or our licensors are unable to secure an exemption to

these manufacturing requirements, if we comply with them, or if we are unable to comply with them, we may

experience a material adverse effect on our competitive position, business, financial conditions, results of

operations and prospects.

Our current proprietary position for certain products and product candidates depends upon our owned

or in-licensed patent filings covering components, manufacturing-related methods, formulations and/or

methods of use, which may not adequately prevent a competitor or other third party from using the same

product candidate for the same or a different use.

Composition of matter patent protection is generally considered to be desirable because it provides protection

without regard to any particular method of use or manufacture or formulation. While we have pursued or

obtained patent protection covering components of certain product candidates and tests, manufacturing-related

methods, formulations and/or methods of use, we have not yet obtained patent protection for all components of

certain product candidates and tests, manufacturing-related methods, formulations and/or methods of use. For

instance, we do not currently have any claims in our owned or in-licensed issued U.S. patents that cover the

overall construct used in our iNeST product candidates. We also cannot be certain that claims in any future

patents issuing from our pending owned or in-licensed patent applications or our future owned or in-licensed

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patent applications will cover the composition of matter, tests, manufacturing-related methods, formulations and/

or methods of use of our current or future product candidates. Method of use patents protect the use of a product

for the specified method and formulation patents cover formulations to deliver therapeutics. These types of

patents do not prevent a competitor or other third party from developing, testing, marketing or commercializing a

similar or identical product for an indication that is outside the scope of the patented method or from developing

a different formulation that is outside the scope of the patented formulation. Moreover, with respect to method of

use patents, even if competitors or other third parties do not actively promote their product for our targeted

indications or uses for which we may obtain patents, physicians may recommend that patients use these

products off-label, or patients may do so themselves. Although off-label use may infringe or contribute to the

infringement of method of use patents, the practice is common and this type of infringement is difficult to prevent

or enforce. Consequently, we may not be able to prevent third parties from practicing our inventions in the United

States or abroad.

Intellectual property rights of third parties could adversely affect our ability to commercialize our

product(s) and product candidates, and we might be required to litigate or obtain licenses from third

parties in order to develop, test or market our product(s) and product candidates.

Because our products and product candidates are still in early stages of development, testing or

commercialization, and one or more features of the products or product candidates, or related technologies such

as their manufacture, formulation, testing or use, may still change, we cannot be confident that we are aware of

all third-party intellectual property that might be relevant to products that we eventually hope to commercialize.

Furthermore, even if all aspects of our product(s) or product candidates, or of other technology, were known, it is

possible that third-party intellectual property, which may or may not currently be public, could develop in a

manner (for example, through issuance of additional patents) that could impede our ability to make or use

relevant products or product candidates, or other technology. Various third-party competitors practice in relevant

spaces, and may have issued patents, or patent applications that will issue as patents in the future, that will

impede or preclude our ability to commercialize products. Furthermore, while U.S. patent laws provide a “safe

harbor” to our clinical product candidates under 35 U.S.C. § 271(e)(1), which exempts from patent infringement

activities related to pursuing FDA approval for a drug product, that exemption expires when an NDA or BLA is

submitted. Accordingly, after such submission (including for certain formulations of our COVID-19 vaccine), the

271(e)(1) safe harbor may no longer provide the same level of protection from third party patent infringement

claims for that product. We may become exposed to lawsuits from third parties who consider our COVID-19

vaccine to infringe their patents. More generally, given the uncertainty of clinical trials, we cannot be certain of

the timing of their completion and it is possible that we might want to submit an NDA or BLA at a time when one

or more relevant third-party patents is in force. Thus, it is possible that at the time that we commercialize our

product candidates, one or more third parties may have issued patent claims that cover such products or critical

features of their production, testing or use. We may not be able to commercialize our products if patents issued

to third parties or other third-party intellectual property rights cover, or may be alleged to cover, our products or

elements thereof, or their methods of manufacture, testing or use at the time that we seek to commercialize

them. In such cases, we may not be in a position to develop, test or commercialize product candidates unless

we successfully pursue litigation to nullify or invalidate the third-party intellectual property right concerned,

successfully design around their claims, or enter into a license agreement with the intellectual property right

holder(s). Such litigation or licenses could be costly, licenses could not be available on commercially reasonable

terms or at all, and design-around could be prohibitively expensive or impossible.

Additionally, with respect to our products, product candidates and related technologies that may play a role in

addressing a pandemic or other public health emergency, it is unclear whether governments around the world

will protect vaccine manufacturers for liability from infringement of third party intellectual property, at least during

the period of such public health emergency. Thus, it is possible that third parties may assert intellectual property

rights against us relating to our COVID-19 vaccine, and that we will not be successful in arguing that

commercialization of our COVID-19 vaccine is exempted from infringement and/or liability for infringement (for

example, under 35 U.S.C. § 271(e)(1), discussed above, or under the Public Readiness and Emergency

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Preparedness Act, or the PREP Act, etc.). Furthermore, even if such commercialization was deemed protected

from infringement during the period of the pandemic crisis, now that various global and U.S. agencies have

declared an end to the global COVID-19 public health emergency, any such exemption may be terminated so

that continuing commercialization could expose us to liability, and might even be precluded if third party(ies) who

hold relevant intellectual property rights are able to secure injunction(s) or are unwilling to license to us on

commercially feasible terms.

It is also possible that we have failed to identify relevant third-party patents that cover, or applications that will

mature into patents that cover, one or more aspects of our platform or product(s) and product candidates. Given

that, in most jurisdictions, a patent application is confidential when initially filed, and typically remains so until it is

published about 18 months after the initial filing, it may not be possible for us to identify certain relevant filings in

time to avoid using the technology that they claim. Additionally, the claims of pending patent applications can,

subject to certain limitations, be amended over time, so that even patent applications whose claims did not cover

our products or activities when published could be amended to cover one or more aspects of our platform or

product candidates over time, and we might not be aware that such amendment had been made.

We may be involved in lawsuits or other legal proceedings to protect or enforce our intellectual property

or the intellectual property of our licensors, or to defend against third-party claims that we infringe,

misappropriate or otherwise violate such third party’s intellectual property, each of which could be

expensive, time consuming and unsuccessful.

There is a substantial amount of litigation, both within and outside the United States, involving patent and other

intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement

lawsuits, interferences, oppositions, ex parte reexaminations, post-grant review, and inter partes review

proceedings before the USPTO and corresponding European and other non-U.S. patent offices.

Competitors and other third parties may infringe, misappropriate or otherwise violate our intellectual property

rights or those of our licensors. To prevent infringement, misappropriation or other unauthorized use, we may be

required to file claims, which can be expensive and time-consuming. In certain instances, we have instituted and

may in the future institute inter partes review proceedings against issued U.S. patents and opposition

proceedings against European patents owned by third parties. We have a number of opposition proceedings

ongoing at the EPO against third-party patents related to mRNA technologies. As the biotechnology and

pharmaceutical industries expand and more patents are issued, the risk increases that our products, product

candidates and services may be subject to claims of infringement of the patent rights of third parties.

In addition, in a patent infringement proceeding, our owned or in-licensed patents may be challenged and a court

may decide that a patent we own or in-license is not valid, is unenforceable and/or is not infringed. If we or any

of our potential future collaborators were to initiate legal proceedings against a third party to enforce a patent

directed at one of our product(s) and/or product candidates, the defendant could counterclaim that our patent is

invalid and/or unenforceable in whole or in part. In patent litigation in the United States, defendant counterclaims

alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include an alleged

failure to meet any of several statutory requirements, including novelty, non-obviousness, enablement or written

description. Grounds for an unenforceability assertion could include an allegation that someone connected with

prosecution of the patent withheld relevant information from the USPTO or made a misleading statement during

prosecution. Third parties may also raise similar claims before the USPTO, even outside the context of litigation.

Similar mechanisms for challenging the validity and enforceability of a patent exist in ex-U.S. patent offices and

may result in the revocation, cancellation or amendment of any ex-U.S. patents we hold in the future. The

outcome following legal assertions of invalidity and unenforceability is unpredictable, and prior art could render

our patents or those of our licensors invalid. If a defendant were to prevail on a legal assertion of invalidity and/or

unenforceability, we could lose at least part, and perhaps all, of the patent protection on a product and/or product

candidate. Such a loss of patent protection would have a material adverse impact on our competitive position,

business, financial conditions, results of operations and prospects.

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Third parties, including our competitors to non-practicing entities or patent assertion entities, may assert that we

are employing their intellectual property and other proprietary technology without authorization. There may be

third-party patents or patent applications with claims to materials, formulations, testing, methods of manufacture

or methods for treatment related to the use, development, testing, manufacture or commercialization of our

COVID-19 vaccine or product candidates. For example, BioNTech SE and certain of our wholly owned

subsidiaries are defendants in litigations initiated by CureVac, Moderna, Arbutus, Genevant, GSK, and

Promosome regarding Comirnaty. See “Legal Proceedings” in this Annual Report. As patent applications can

take many years to issue, there may be currently pending patent applications which may later result in issued

patents that our product(s) and/or product candidates may infringe. In addition, third parties may obtain patents

in the future and claim that our technologies infringe upon these patents. If any third-party patents were held by a

court of competent jurisdiction to cover the testing or manufacturing processes of any of our product(s) and/or

product candidates, any molecules formed during the testing and manufacturing processes or any final product

itself, the holders of any such patents may obtain injunctive or other equitable relief, which could effectively block

our ability to develop, test and commercialize such product and/or product candidate unless we obtained a

license under the applicable patents, or until such patents expire. Similarly, if any third-party patents were held

by a court of competent jurisdiction to cover aspects of our formulations, processes for testing or manufacture or

methods of use, including combination therapy, the holders of any such patents may be able to block our ability

to develop, test and commercialize the applicable product and/or product candidate unless we obtained a license

or until such patent expires. In either case, such a license may not be available on commercially reasonable

terms, or at all, or may be non-exclusive.

Interference or derivation proceedings provoked by third parties or brought by us or declared by the USPTO may

be necessary to determine the priority of inventions with respect to our patents or patent applications or those of

our licensors. An unfavorable outcome could require us to cease using the related technology or to attempt to

license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer

us a license on commercially reasonable terms or at all, or if a non-exclusive license is offered and our

competitors gain access to the same intellectual property and technology. Our defense of litigation, interference,

derivation or similar proceedings may fail and, even if successful, may result in substantial costs and distract our

management, technical personnel and other employees. In addition, the uncertainties associated with litigation

could have a material adverse effect on our ability to raise the funds we need to continue our clinical trials and

research programs, to license necessary technology from third parties or to enter into development or

manufacturing collaborations that would help us bring our product(s) and/or product candidates to market.

Even if resolved in our favor, litigation or other legal proceedings relating to our intellectual property rights may

cause us to incur significant expenses, and could distract our management, technical personnel and other

employees from their normal responsibilities. Such proceedings could substantially increase our operating losses

and reduce the resources available for development activities or any future sales, marketing or distribution

activities. We may not have sufficient financial or other resources to conduct such proceedings adequately.

Some of our competitors may be able to sustain the costs of such proceedings more effectively than we can

because of their greater resources in one or more aspects, or for other reasons. Uncertainties resulting from the

initiation and continuation of patent litigation or other proceedings could compromise our ability to compete in the

marketplace.

In the event of a successful claim of infringement, misappropriation or other violation against us, we may have to

pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties,

redesign our infringing products, or obtain one or more licenses from third parties, which may not be made

available on commercially favorable terms, if at all, or may require substantial time and expense.

Such licenses are likely to be non-exclusive and, therefore, our competitors may have access to the same

intellectual property and technology licensed to us. If we fail to obtain a required license and are unable to

design around a patent, we may be unable to effectively market some of our technology and product(s) and/or

product candidates, which could limit our ability to generate revenues or achieve or maintain profitability and

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possibly prevent us from generating revenue sufficient to sustain our operations. Moreover, certain of our

collaborations provide, and we expect additional collaborations to provide, that royalties payable to us for

licenses to our intellectual property may be offset by amounts paid by our collaborators to third parties for

licenses to such third parties’ intellectual property in the relevant fields, which could result in significant

reductions in our revenues from products developed through collaborations.

In addition, in connection with certain license and collaboration agreements, we have agreed to indemnify certain

third parties for certain costs incurred in connection with litigation relating to intellectual property rights or the

subject matter of the agreements. The cost to us of any litigation or other proceeding relating to intellectual

property rights, even if resolved in our favor, could be substantial.

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. There could also be public announcements of the results of hearings, motions or other interim

proceedings or developments in any litigation or other intellectual property proceedings. If securities analysts or

investors perceive these results to be negative, the price of the ADSs representing our ordinary shares could

decline.

Obtaining and maintaining our 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.

Periodic maintenance fees, renewal fees, annuity fees, and various other governmental fees on patents and

applications will be due to be paid to the USPTO and various governmental patent agencies outside of the

United States in several stages over the lifetime of the patents or applications. We have systems in place to

remind us to pay these fees and we employ an outside firm and rely on our outside counsel to pay these fees

due to non-U.S. patent agencies; however, we cannot guarantee that we will successfully pay these fees. The

USPTO and various non-U.S. governmental patent agencies require compliance with a number of procedural,

documentary, fee payment, and other similar provisions during the patent application process. We employ

reputable law firms and other professionals to help us comply, and in many cases, an inadvertent lapse can be

cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are

situations in which non-compliance 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. We are also dependent on our

licensors to take the necessary action to comply with these requirements with respect to our in-licensed

intellectual property, and we cannot guarantee that they will do so. In such an event, our competitors might be

able to enter the market with similar or identical products or technology, and this would have a material adverse

impact on our business, financial condition, results of operations and prospects.

Changes in patent law in the United States or in other countries could diminish the value of patents in

general, thereby impairing our ability to protect our products.

As is the case with other biotechnology companies, our success is heavily dependent on our intellectual property

rights, particularly patents that we own and in-license. Obtaining and enforcing patents in the biotechnology

industry involve both technological and legal complexity, and therefore obtaining and enforcing biotechnology

patents is costly, time-consuming and inherently uncertain. Moreover, there are periodic changes in patent law.

For example, after March 2013, under the America Invents Act, the United States transitioned to a first inventor

to file system in which, assuming that other requirements for patentability are met, the first inventor to file a

patent application will be entitled to the patent on an invention regardless of whether a third party was the first to

invent the claimed invention. The America Invents Act also includes a number of significant changes that have

affected the way patent applications are prosecuted and also affect patent litigation. Such legislation and its

implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications

and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our

business, financial condition, results of operations and prospects.

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In addition, decisions by courts and governmental bodies in the United States and other jurisdictions may affect

the value of patent applications, issued patents or other intellectual property that we own or in-license. For

example, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain

circumstances and weakened the rights of patent owners in certain situations. 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 decisions by the U.S. Congress,

the federal courts, the USPTO and other administrative agencies, and their equivalents in other jurisdictions, the

laws and regulations governing patents could change in unpredictable ways that could have a material adverse

effect on our existing patent portfolio and our ability to obtain, maintain, protect, defend or enforce our intellectual

property in the future.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position

would be harmed.

In addition to seeking patent protection for some of our technology, product(s) and product candidates, we also

seek to rely on trade secret protection and confidentiality agreements to maintain our competitive position and

protect proprietary know-how that is not patentable, processes for which patents are difficult to enforce and any

other elements of our product discovery development, testing, manufacturing and commercialization processes

that involve proprietary know-how, information or technology that is not covered by patents. However, trade

secrets and know-how may be difficult to protect.

We seek to protect these trade secrets, know-how and other proprietary technology, in part, by entering into non-

disclosure and confidentiality agreements with parties who have access to them, such as our employees,

corporate collaborators, outside scientific collaborators, CROs, CMOs, consultants, advisors and other third

parties. We also enter into confidentiality and invention or patent assignment agreements with our employees

and consultants and require all of our employees and key consultants who have access to our trade secrets,

proprietary know-how, information or technology to enter into confidentiality agreements. We cannot guarantee

that we have entered into such agreements with each party that may have or have had access to our trade

secrets or proprietary technology and processes. To the extent we become involved in litigation that may require

discovery of our trade secrets, know-how and other proprietary technology, we seek to secure protective orders

from the court that bind the parties with access to the discovered information. Despite our best efforts, we cannot

be certain that our trade secrets and other confidential proprietary information will not be disclosed or that

competitors will not otherwise gain access to our trade secrets or independently develop substantially equivalent

information and techniques. Any of these parties who may have access to our trade secrets, know-how and

other proprietary technology may breach such agreements or orders. For example, a former employee of our

COVID-19 vaccine collaborator, Pfizer, has reportedly misappropriated trade secrets on our COVID-19 vaccine.

We may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally

disclosed or misappropriated a trade secret or know-how is difficult, expensive and time-consuming, and the

outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or

unwilling to protect trade secrets and know-how. In addition, we cannot be certain that our proprietary technical

information and related confidential documents that we have shared with our collaborators and/or have

submitted to governmental agencies, including regulatory agencies, for evaluation and supervision of

pharmaceutical products will be kept confidential. For example, certain documents relating to our COVID-19

vaccine were unlawfully accessed after a cyberattack on the EMA in December 2020. If any of our trade secrets

or know-how were to be lawfully obtained or independently developed by a competitor or other third party, we

would have no right to prevent them from using that technology or information to compete with us. If we are

unable to prevent unauthorized material disclosure of our intellectual property to third parties, we may not be

able to establish or maintain a competitive advantage in our market, which could materially adversely affect our

business, operating results, financial condition and prospects.

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We may be subject to claims that we have wrongfully hired an employee from a competitor, or that our

employees, consultants or independent contractors have wrongfully used or disclosed confidential

information of third parties, including alleged trade secrets of their former employers.

We have received confidential and proprietary information from third parties in the course of our research and

other collaborations with others in the industry, academic institutions and other third parties. In addition, many of

our employees, consultants and advisors are currently or were previously employed at universities or other

biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try

to ensure that our employees, consultants, independent contractors and advisors do not use the confidential or

proprietary information, trade secrets or know-how of others in their work for us, we may be subject to claims

that we have inadvertently or otherwise used or disclosed confidential or proprietary information, trade secrets or

know-how of these third parties, or that our employees, consultants, independent contractors or advisors have

inadvertently or otherwise used or disclosed confidential information, trade secrets or know-how of such

individual’s current or former employer. If we fail in defending any such claims, in addition to paying monetary

damages, we may lose valuable intellectual property rights or personnel. Litigation may be necessary to defend

against these claims. Even if we are successful in defending against these claims, litigation could result in

substantial cost and be a distraction to our management, technical personnel and other employees. Claims that

we or our employees, consultants or advisors have misappropriated the confidential or proprietary information,

trade secrets or know-how of third parties could have a material adverse effect on our business, financial

condition, results of operations and prospects.

We may be subject to claims challenging the inventorship or ownership of our patents and other

intellectual property.

In the future, we may be subject to claims that current or former employees, consultants, independent

contractors, collaborators or other third parties have an interest in our patents or other intellectual property as an

inventor or co-inventor. While it is our policy to require our employees, consultants, independent contractors,

collaborators and other third parties who may be involved in the conception, development or reduction to

practice of intellectual property to execute agreements assigning such intellectual property to us, we may be

unsuccessful in executing such an agreement with each party who, in fact, conceives, develops or reduces to

practice such intellectual property that we regard as our own. In addition, certain such agreements, even if

successfully executed may distribute ownership or control of intellectual property rights between or among

parties, for example based on subject matter, relationship to other intellectual property, and/or one or more

aspects of development of the intellectual property; after the agreements are in place disputes may arise over

such distribution principles or over proper treatment of particular developed intellectual property in accordance

with them. Disagreements may be difficult or impossible to resolve, may be expensive to address, and may

result in our failing to secure or maintain ownership in or control of intellectual property necessary or important to

our business.

The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be

breached. For example, we may have inventorship or ownership disputes arise from conflicting obligations of

employees, consultants, independent contractors, collaborators or other third parties who are involved in

developing and commercializing our product(s) and/or product candidates. Litigation may be necessary to

defend against these and other claims challenging inventorship or ownership. If we fail in defending any such

claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as

exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material

adverse effect on our business, operating results and financial condition. Even if we are successful in defending

against such claims, litigation could result in substantial costs and be a distraction to management, technical

personnel and other employees.

Furthermore, the laws of some other countries do not protect intellectual property and other proprietary rights or

establish ownership of inventions to the same extent or in the same manner as the U.S. laws. A majority of our

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employees work in Germany and are subject to German employment law. Ideas, developments, discoveries and

inventions made by such employees are subject to the provisions of the German Act on Employees’ Inventions,

which regulates the ownership of, and compensation for, inventions made by employees. We face the risk that

disputes can occur between us and our employees or former employees pertaining to alleged non-adherence to

the provisions of this act that may be costly to defend and take up our management’s, technical personnel’s and

other employees’ time and efforts whether we prevail or fail in any such dispute. There is a risk that the

compensation we provided to employees who assign patents to us may be deemed to be insufficient and we

may be required under German law to increase the compensation due to such employees for the use of the

patents. In those cases, where employees’ rights have not been assigned to us, we may need to pay

compensation for the use of those patents. If we are required to pay additional compensation or face other

disputes under the German Act on Employees’ Inventions, our business, results of operations and financial

condition could be adversely affected.

We will not seek to protect our intellectual property rights in all jurisdictions throughout the world, and

we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where

we seek protection.

Filing, prosecuting and defending patents on product(s) and/or product candidates in all countries throughout the

world would be prohibitively expensive, and our intellectual property rights in some countries outside the United

States, particularly those in Asia, including China, can be less extensive than those in the United States. In

addition, the laws of some countries do not protect intellectual property rights to the same extent as laws in

Germany and the United States. Consequently, we may not be able to prevent third parties from practicing our

inventions in all countries outside the United States to the same extent as within the United States, or from

selling or importing products made using our inventions in and to the United States or other jurisdictions.

Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop

their own product candidates and further, may export otherwise infringing products to territories where we have

patent protection, but enforcement is not as strong as that in the United States. These products may compete

with our product(s) and/or product candidates, and our patents or other intellectual property rights may not be

effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights

in certain jurisdictions, particularly outside of Europe and the United States. The legal systems of certain

countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets and

other intellectual property protection, particularly those relating to biotechnology products, which could make it

difficult for us to stop the infringement, misappropriation or other violation of our patents and other intellectual

property or development, testing, marketing and commercialization of competing products in violation of our

owned or in-licensed intellectual property and other proprietary rights generally. Proceedings to enforce our

intellectual property rights in such jurisdictions could result in substantial costs and divert our efforts and

attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted

narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against

us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may

not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the

world may be inadequate to obtain a significant commercial advantage from the intellectual property that we

develop or in-license. In particular, the validity, enforceability and scope of protection of intellectual property in

China, where we derive net sales and maintain collaboration partnerships including licensing, are still evolving

and historically, have not protected and may not protect in the future, intellectual property rights to the same

extent as laws developed in Europe, including Germany, and the United States. Consequently, the time required

to enforce our intellectual property rights in the legal regime of China may be lengthy and delay our recovery.

Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses

to third parties. In addition, many countries limit the enforceability of patents against government agencies or

government contractors. In these countries, the patent owner may have limited remedies, which could materially

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diminish the value of such patent. If we or any of our licensors is 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.

If our trademarks and trade names are not adequately protected, 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. We may not be able to protect our rights to these

trademarks and trade names, which we need to build name recognition among potential collaborators or

customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours

or collaborators may fail to use our trade names or trademarks appropriately or at all, thereby impeding our

ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade

name or trademark infringement claims brought by owners of other 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, we may not be able to compete

effectively and our business may be adversely affected. We may license our trademarks and trade names to

third parties, such as distributors and collaborators. Though these license agreements may provide guidelines

for how our trademarks and trade names may be used, a breach of these agreements or misuse or failure to use

of our trademarks and trade names by our licensees may jeopardize our rights in or diminish the goodwill

associated with our trademarks, and trade names. Our efforts to enforce or protect our proprietary rights related

to trademarks, trade names, trade secrets, know-how, domain names, copyrights 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.

Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

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 COVID-19 vaccines or therapies, and/or individualized cancer immunotherapies

that are similar to our COVID-19 vaccine and/or any product candidates we may develop and commercialize

or utilize similar technologies that are not covered by the claims of the patents that we now or may in the

future own or have exclusively in-licensed;

–we, our co-owners or our licensors or future collaborators might not have been the first to make the inventions

covered by the issued patents or pending patent applications that we own or have exclusively in-licensed;

–we, our co-owners or our licensors or future 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 our owned or in-licensed intellectual property rights;

–it is possible that our pending patent applications or those that we may own or in-license in the future will not

lead to issued patents;

–claims of issued patents that we own or have exclusively in-licensed may be held invalid or unenforceable,

including as a result of legal challenges by our competitors;

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–our competitors might conduct research, development, testing or commercialization activities in countries

where we do not have patent rights and then use the information learned from such activities to develop

competitive products for sale in our major commercial markets;

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

–the patents of others may have an adverse effect on our business; and

–we may choose not to file a patent 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.

Risks Related to Government Regulation

We may not be able to develop or obtain approval for companion diagnostics required for

commercialization of some of our product candidates.

Administration of some of our product candidates may require the use of immuno-assays and bioinformatic tools

in which patients are screened for optimal target antigens of our product candidates. If safe and effective use of

a biologic product depends on an in vitro diagnostic, then the FDA generally requires approval or clearance of

the diagnostic, known as a companion diagnostic, concurrently with approval of the therapeutic product. To date,

the FDA has generally required in vitro companion diagnostics intended to select the patients who will respond to

cancer treatment to obtain a pre-market approval, or PMA, for that diagnostic, which can take up to several

years, simultaneously with approval of the biologic product. Similarly, in the European Union, an in vitro

companion diagnostic may be placed on the market only if it conforms to certain “essential requirements” and

bears the Conformité Européene Mark, or CE Mark. The conformity assessment process to obtain the CE Mark

can be lengthy and we may fail to demonstrate such conformity. Further, the applicable regulatory framework for

in vitro diagnostics in the EU changed in May 2022 when a new EU regulation with stricter regulatory

requirements for in vitro diagnostics became applicable. Under the regulation, all new in vitro companion

diagnostics must undergo conformity assessment by a notified body prior to obtaining their CE Mark.

For our individualized immunotherapy candidates, the FDA and comparable regulatory authorities outside of the

United States may require the development and regulatory approval of a companion diagnostic assay as a

condition to approval. The FDA may require original or supplemental PMA approvals for use of that same

companion diagnostic as a condition of approval of additional individualized therapeutic candidates. We do not

have experience or capabilities in developing or commercializing companion diagnostics and plan to rely in large

part on third parties to perform these functions. Companion diagnostic assays are subject to regulation by the

FDA and other comparable regulatory authorities in other jurisdictions as medical devices and require separate

regulatory approval prior to the use of such diagnostic assays with our individualized therapeutic candidates. If

we, or any third parties that we engage to assist us, are unable to successfully develop companion diagnostic

assays for use with our individualized therapeutic candidates, or are unable to obtain regulatory approval or

experience delays in either development or obtaining regulatory approval, we may be unable to identify patients

with the specific profile targeted by our product candidates for enrollment in our clinical trials. Accordingly, further

investment may be required to further develop or obtain the required regulatory approval for the relevant

companion diagnostic assay, which would delay or substantially impact our ability to conduct additional clinical

trials or obtain regulatory approval.

Because we are developing some of our product candidates for the treatment of diseases in which there

is little clinical experience and, in some cases, using new endpoints or methodologies, the FDA, the EMA

or other regulatory authorities may not consider the endpoints of our clinical trials to provide clinically

meaningful results.

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There may not be pharmacologic therapies approved to treat the underlying causes of many diseases that we

may address in the future. For instance, we and our collaborators are applying our technology to develop

therapeutics in indications such as certain rare diseases, including some for which no or few clinical trials have

been attempted. As a result, any future design and conduct of clinical trials of product candidates for the

treatment of certain rare diseases may take longer, be more costly, or be less effective as part of the novelty of

development in these diseases. Even if we decide to conduct clinical trials and the FDA does find our success

criteria to be sufficiently validated and clinically meaningful, we may not achieve the pre-specified endpoint to a

degree of statistical significance in any pivotal or other clinical trials we or our collaborators may conduct for our

programs. Further, even if we do achieve the pre-specified criteria, our trials may produce results that are

unpredictable or inconsistent with the results of the more traditional efficacy endpoints in the trial. The FDA also

could give overriding weight to other efficacy endpoints over a primary endpoint, even if we achieve statistically

significant results on that endpoint, if we do not do so on our secondary efficacy endpoints. The FDA also weighs

the benefits of a product against its risks and the FDA may view the efficacy results in the context of safety as

not being supportive of licensure. Other regulatory authorities in Europe and other jurisdictions may make similar

findings with respect to these endpoints.

The FDA, the EMA or other comparable regulatory authorities may disagree with our regulatory plan and

we may fail to obtain regulatory approval of our product candidates.

If the results of our clinical trials are sufficiently compelling, we or our collaborators intend to discuss with the

FDA and regulatory authorities in other countries the submission of a BLA or respective applications in other

countries for our product candidates. However, we do not have any agreement or guidance from the FDA that

our regulatory development plans will be sufficient for submission of a BLA for any of our product candidates.

The FDA, the EMA or other regulatory agencies may grant accelerated approval for our product candidates and,

as a condition for accelerated approval, the FDA, the EMA or other regulatory agencies may require a sponsor of

a drug or biologic receiving accelerated approval to perform post-marketing studies to verify and describe the

predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug or biologic may be

subject to withdrawal procedures by the FDA, the EMA or other regulatory agencies that are more accelerated

than those available for regular approvals. In addition, the standard of care may change with the approval of new

products in the same indications that we are studying. This may result in the FDA, the EMA or other regulatory

agencies requesting additional studies to show that our product candidate is superior to the new products.

Our clinical trial results may also not support approval. In addition, our product candidates could fail to receive

regulatory approval for many reasons, including the following:

–the FDA, the EMA or comparable regulatory authorities may disagree with the design or implementation of our

clinical trials;

–we may be unable to demonstrate to the satisfaction of the FDA, the EMA or comparable regulatory

authorities that our product candidates are safe and effective for any of their proposed indications;

–the results of clinical trials may not meet the level of statistical significance required by the FDA, the EMA or

comparable regulatory authorities for approval, including due to the heterogeneity of patient populations;

–we may be unable to demonstrate that our product candidates’ clinical and other benefits outweigh their safety

risks;

–the FDA, the EMA or comparable regulatory authorities may disagree with our interpretation of data from

preclinical studies or clinical trials;

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–the data collected from clinical trials of our product candidates may not be sufficient to the satisfaction of the

FDA, the EMA or comparable regulatory authorities to support the submission of a BLA or other comparable

submissions or to obtain regulatory approval in the United States or elsewhere;

–the FDA, the EMA or comparable regulatory authorities will inspect our manufacturing facilities and may not

approve our facilities or our manufacturing processes and controls;

–the approval policies or regulations of the FDA, the EMA or comparable regulatory authorities may significantly

change in a manner rendering our clinical data insufficient for approval; and

–appointees of the presidential administration in the United States may seek to change regulatory requirements

for the approval of products or the approach to the review of product applications.

We may not be able to file INDs with the FDA, clinical trial applications with the competent authorities of

the member states of the European Union or similar applications with other comparable regulatory

authorities to commence additional clinical trials on the timelines we expect, and even if we are able to,

one or more of these regulatory authorities may not permit us to proceed.

The timing of filing on our product candidates is dependent on further preclinical, clinical and manufacturing

success. We cannot be sure that submission of an IND or IND amendment with the FDA, a clinical trial

application with the regulatory authorities of the EU member states or similar application with other comparable

regulatory authorities will result in the FDA, the regulatory authorities of the EU member states or any

comparable regulatory authority allowing testing and clinical trials to begin, or that, once begun, issues will not

arise that result in the suspension or termination of such clinical trials. Additionally, even if such regulatory

authorities agree with the design and implementation of the clinical trials set forth in an IND, clinical trial

application or similar applications, we cannot guarantee that such regulatory authorities will not change their

requirements in the future.

We may seek Orphan Drug Designation for some or all of our product candidates across various

indications, but we may be unable to obtain such designations or to maintain the benefits associated

with Orphan Drug Designation, including market exclusivity, which may cause our revenue, if any, to be

reduced.

Our strategy includes filing for Orphan Drug Designation where available for our product candidates. Under the

U.S. Orphan Drug Act, the FDA may grant Orphan Drug Designation to a drug or biologic intended to treat a rare

disease or condition, which is defined as one occurring in a patient population of fewer than 200,000 in the

United States, or a patient population of 200,000 or greater in the United States where there is no reasonable

expectation that the cost of developing the drug or biologic will be recovered from sales in the United States. In

the United States, Orphan Drug Designation entitles a party to financial incentives, such as opportunities for

grant funding toward clinical trial costs, tax advantages, and user-fee waivers. In addition, if a product that has

Orphan Drug Designation subsequently receives the first FDA approval for the disease for which it has such

designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any

other applications, including a full new drug application or a BLA, to market the same drug or biologic for the

same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the

product with orphan drug exclusivity or where the original manufacturer is unable to assure sufficient product

quantity. Similar rules apply in the European Union with respect to drugs or biologics designated as orphan

medicinal products.

In addition, exclusive marketing rights in the United States may be limited if we seek approval for an indication

broader than the orphan-designated indication or may be lost if the FDA later determines that the request for

designation was materially defective. Further, even if we obtain orphan drug exclusivity for a product, that

exclusivity may not protect the product effectively from competition because different drugs with different active

moieties may receive and be approved for the same condition, and only the first applicant to receive approval will

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receive the benefits of marketing exclusivity. Even after an orphan-designated product is approved, the FDA can

subsequently approve a later drug with the same active moiety for the same condition if the FDA concludes that

the later drug is clinically superior if it is shown to be safer, more effective, or makes a major contribution to

patient care. Similar considerations apply in the European Union with respect to drugs or biologics designated as

orphan medicinal products. Orphan Drug Designation neither shortens the development time or regulatory

review time of a drug, nor gives the drug any advantage in the regulatory review or approval process. In addition,

while we may seek Orphan Drug Designation for our product candidates, we may never receive such

designations.

We may seek Breakthrough Therapy or Fast Track designation for one or more of our product

candidates, but we may not receive such designations. Even if we do, it may not lead to a faster

development or regulatory review or approval process, and it may not increase the likelihood that such

product candidates will receive marketing approval.

We may seek a Breakthrough Therapy Designation in the United States for one or more of our product

candidates. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or

more other drugs, 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. For

drugs that have been designated as breakthrough therapies, interaction and communication between the FDA

and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing

the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by

the FDA are also eligible for priority review if supported by clinical data at the time of the submission of the BLA.

Although priority review shortens the goal date by which FDA intends to decide on an application, it does not

guarantee any particular action by FDA, or even FDA action by that date.

Designation as a breakthrough therapy is at the discretion of the FDA. Accordingly, even if we believe that one of

our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and

instead determine not to make such designation. In any event, the receipt of a Breakthrough Therapy

Designation for a drug may not result in a faster development process, review or approval compared to drugs

considered for approval under conventional FDA procedures and it would not assure ultimate approval by the

FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may

later decide that the product candidate no longer meets the conditions for qualification or it may decide that the

time period for FDA review or approval will not be shortened.

We may also seek Fast Track Designation in the United States for some of our product candidates. If a therapy

is intended for the treatment of a serious or life-threatening condition and the therapy demonstrates the potential

to address significant unmet medical needs for this condition, the drug sponsor may apply for Fast Track

Designation. The FDA has broad discretion whether to grant this designation, and even if we believe a particular

product candidate is eligible for this designation, we cannot be sure that the FDA would decide to grant it. Even if

we do receive Fast Track Designation, we may not experience a faster development process, review or approval

compared to conventional FDA procedures. The FDA may withdraw Fast Track Designation if it believes that the

designation is no longer supported by data from our clinical development program. Fast Track Designation alone

does not guarantee qualification for the FDA’s priority review procedures.

We expect some of the product candidates we develop will be regulated as biologics in the United States

and therefore they may be subject to competition from biosimilars approved through an abbreviated

regulatory pathway.

The ACA includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or the BPCIA,

which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable

with an FDA-approved reference biological product. Under the BPCIA, an application for a biosimilar product

may not be submitted to the FDA until four years following the date that the reference product was first approved

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by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years

from the date on which the reference product was first approved.

During this 12-year period of exclusivity, another company may still market a competing version of the reference

product if the FDA approves a BLA for the competing product containing the sponsor’s own preclinical data and

data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of the other

company’s product. The law is complex and is still being interpreted and implemented by the FDA. As a result, its

ultimate impact, implementation and meaning are subject to uncertainty.

We believe that any of our product candidates approved as a biological product under a BLA should qualify for a

12-year period of exclusivity. However, there is a risk that this exclusivity could be shortened due to

congressional action or otherwise, or that the FDA will not consider our product candidates to be reference

products for competing products, potentially creating the opportunity for generic competition sooner than

anticipated. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also

been the subject of recent litigation. Moreover, the extent to which a biosimilar, once approved, will be

substituted for any one of our reference products in a way that is similar to traditional generic substitution for

non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that

are still developing.

The regulatory landscape that will govern our product candidates is uncertain. Regulations relating to

more established gene therapy and cell therapy products are still developing, and changes in regulatory

requirements could result in delays or discontinuation of development of our product candidates or

unexpected costs in obtaining regulatory approval.

The regulatory requirements to which our product candidates will be subject are not entirely clear. Even with

respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory

landscape is still developing. For example, regulatory requirements governing gene therapy products and cell

therapy products have changed frequently and may continue to change in the future. Moreover, there is

substantial, and sometimes uncoordinated, overlap in those responsible for regulation of existing gene therapy

products and cell therapy products. Although the FDA decides whether individual gene therapy protocols may

proceed, the review process and determinations of other reviewing bodies can impede or delay the initiation of a

clinical study, even if the FDA has reviewed the study and approved its initiation. Conversely, the FDA can place

an IND application on clinical hold even if such other entities have provided a favorable review. Furthermore,

gene therapy clinical trials are also subject to review and oversight by an institutional biosafety committee, a

local institutional committee that reviews and oversees basic and clinical research conducted at the institution

participating in the clinical trial. In addition, adverse developments in clinical trials of gene therapy products

conducted by others may cause the FDA or other regulatory bodies to change the requirements for approval of

any of our product candidates.

Complex regulatory environments exist in other jurisdictions in which we might consider seeking regulatory

approvals for our product candidates, further complicating the regulatory landscape. For example, in the

European Union, a special committee called the Committee for Advanced Therapies was established within the

EMA in accordance with Regulation (EC) No 1394/2007 on advanced-therapy medicinal products, or ATMPs, to

assess the quality, safety and efficacy of ATMPs, and to follow scientific developments in the field. ATMPs

include gene therapy products as well as somatic cell therapy products and tissue engineered products.

These various regulatory review committees and advisory groups and new or revised guidelines that they

promulgate from time to time may lengthen the regulatory review process, require us to perform additional

studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or

prevent approval and commercialization of our product candidates or lead to significant post-approval limitations

or restrictions. As the regulatory landscape for our CAR-T-cell immunotherapy product candidates is new, we

may face even more cumbersome and complex regulations than those emerging for gene therapy products and

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cell therapy products. Furthermore, even if our product candidates obtain required regulatory approvals, such

approvals may later be withdrawn as a result of changes in regulations or the interpretation of regulations by

applicable regulatory agencies.

Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential

product to market could decrease our ability to generate sufficient product sales revenue to maintain our

business.

We may be unable to obtain regulatory approval for our product candidates under applicable

international regulatory requirements.

The denial or delay of such approval would delay commercialization of our product candidates and adversely

impact our potential to generate revenue, our business and our results of operations.

Approval by the FDA in the United States, if obtained, does not ensure approval by regulatory authorities in other

countries or jurisdictions. In order to market our products or product candidates in any other jurisdiction, we must

establish and comply with numerous and varying regulatory requirements on a jurisdiction-by-jurisdiction basis

regarding safety and efficacy. In addition, clinical trials conducted in one country may not be accepted by

regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory

approval in any other country. Approval processes vary among countries and can involve additional product

testing and validation and additional administrative review periods.

Seeking regulatory approval in other jurisdictions could result in difficulties and costs for us and require

additional preclinical studies or clinical trials which could be costly and time-consuming. Regulatory requirements

can vary widely from country to country and could delay or prevent the introduction of our products in those

countries. The European Union and other jurisdictions’ regulatory approval processes involve all of the risks

associated with the FDA approval. If we fail to comply with regulatory requirements in certain markets or to

obtain and maintain required approvals, or if regulatory approvals in certain markets are delayed, our target

market will be reduced and our ability to realize the full market potential of our products will be unrealized.

Certain jurisdictions may have submission requirements for drug clinical trial and marketing applications that

require us or our partners to submit substantial detailed materials related to non-clinical and clinical development

and manufacturing and quality control to drug regulators or testing laboratories. This can include confidential

standard operating procedures or executed batch records for the production of biological products or other

records or documents that set forth detailed information about the manufacturing process and the manufacturing

site. If these materials are disclosed in an unauthorized manner, lost, or otherwise diverted to third parties or

competitors during the application preparation process, this could negatively affect our ability to protect our

intellectual property.

Our partners in different countries are subject to local regulatory requirements and standards on the

manufacturing and distribution of drugs and the implementation of clinical and non-clinical research. These

include but are not limited to good manufacturing, distribution, laboratory, clinical practice, and

pharmacovigilance rules. If these companies do not comply with applicable standards, they could become the

subjects of inspections, investigations and enforcement, including orders to cease the activities pending

remediation that is acceptable to the government. Such an order or other similar enforcement could interfere with

our clinical development and marketing activities both in that jurisdiction and others, if it impacts supply or the

quality and transfer of data.

A third-party investigational product candidate used in combination with our product candidates may be

unable to obtain regulatory approval, which may delay commercialization of our product candidates.

We are developing several of our product candidates to be used in combination with our and third-party product

candidates. Even if any product candidate we develop were to receive marketing approval or be commercialized

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for use in combination with other existing products, we would continue to be subject to the risks that the FDA, the

EMA or comparable regulatory authorities in other jurisdictions could revoke approval of the product used in

combination with our product or that safety, efficacy, manufacturing or supply issues could arise with any of those

existing products. If the products or product candidates we use in combination with our product candidates are

replaced as the standard of care for the indications we choose for any of our product candidates, the FDA, the

EMA or comparable regulatory authorities in other jurisdictions may require us to conduct additional clinical trials.

The occurrence of any of these risks could result in our own products, if approved, being removed from the

market or being less successful commercially. We also plan to evaluate current and future product candidates in

combination with one or more product candidates that have not yet been approved for marketing by the FDA, the

EMA or comparable regulatory authorities in other jurisdictions. We will not be able to market any product

candidate we develop in combination with an unapproved product candidate if that unapproved product

candidate does not ultimately obtain marketing approval. In addition, unapproved product candidates face the

same risks described with respect to our product candidates currently in development and clinical trials, including

the potential for serious adverse effects, delay in their clinical trials and lack of FDA, EMA or comparable

regulatory authority approval.

If the FDA, the EMA or comparable regulatory authorities in other jurisdictions do not approve these other

product candidates or revoke their approval of, or if safety, efficacy, manufacturing or supply issues arise with,

the products or product candidates we choose to evaluate in combination with any product candidate we

develop, we may be unable to obtain approval of or market any product candidate we develop.

Some of our product candidates are classified as gene therapies by the FDA and the EMA, and the FDA

has indicated that our product candidates will be reviewed within its Center for Biologics Evaluation and

Research, or CBER. Even though our mRNA product candidates are designed to have a different

mechanism of action from gene therapies, the association of our product candidates with gene therapies

could result in increased regulatory burdens, impair the reputation of our product candidates, or

negatively impact our platform or our business.

There have been few approvals of gene therapy products in the United States and other jurisdictions, and there

have been well-reported significant adverse events associated with their testing and use. Gene therapy products

have the effect of introducing new DNA and potentially irreversibly changing the DNA in a cell. In contrast, mRNA

is highly unlikely to localize to the nucleus, be reverse transcribed or integrated into the genome. Consequently,

we expect that our products or product candidates will have a different potential side effect profile from gene

therapies because they lack risks associated with altering cell DNA irreversibly. Further, we may avail ourselves

of ways of mitigating side effects in developing our products and product candidates to address safety concerns

that are not available to other products or product candidates classified as gene therapies, such as lowering the

dose of our products or product candidates during repeat dosing or stopping treatment to potentially ameliorate

undesirable side effects.

Regulatory requirements governing gene and cell therapy products have evolved and may continue to change in

the future, and the implications for mRNA-based therapies is unknown. For example, the FDA has established

the Office of Tissues and Advanced Therapies within CBER to consolidate the review of gene therapy and

related products, and convenes the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER

on its review. In the European Union, mRNA has been characterized as a gene therapy medicinal product. In

certain countries, mRNA therapies have not yet been classified or any such classification is not known to us.

Notwithstanding the differences between our mRNA product candidates and gene therapies, the classification of

some of our mRNA product candidates as gene therapies in the United States, the European Union and

potentially other counties could adversely impact our ability to develop our product candidates, and could

negatively impact our platform and our business. For instance, a potential future clinical hold on gene therapy

products across the field due to risks associated with altering cell DNA irreversibly could apply to our mRNA

product candidates irrespective of the mechanistic differences between gene therapies and mRNA.

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Adverse events reported with respect to gene therapies or genome editing therapies could adversely impact one

or more of our programs. Although our mRNA product candidates are designed not to make any permanent

changes to cell DNA, regulatory agencies or others could believe that adverse effects of gene therapy products

caused by introducing new DNA and irreversibly changing the DNA in a cell could also be a risk for our approved

mRNA products or investigational therapies, and as a result may delay one or more of our trials or impose

additional testing for long-term side effects. Any new requirements and guidelines promulgated by regulatory

review agencies may have a negative effect on our business by lengthening the regulatory review process,

requiring us to perform additional or larger studies, or increasing our development costs, any of which could lead

to changes in regulatory positions and interpretations, delay or prevent advancement or approval and

commercialization of our product candidates or lead to significant post-approval studies, limitations or

restrictions. As we advance our product candidates, we will be required to consult with these regulatory agencies

and advisory committees and comply with applicable requirements and guidelines. If we fail to do so, we may be

required to delay or discontinue development of some or all of our product candidates.

Our COVID-19 vaccine and any other product candidates for which we receive approval or emergency

use authorization are subject to continuing regulatory oversight, and we will be subject to ongoing

regulatory obligations and continued regulatory review, which may result in significant additional

expense. We may be subject to penalties if we fail to comply with regulatory requirements or experience

unanticipated problems with our products or product candidates.

Our COVID-19 vaccine and any other product candidates for which we receive approval or emergency use

authorization are subject to continuing regulatory oversight, including the review of additional safety information,

and the applicable regulatory authority may still impose significant restrictions on the indicated uses or marketing

of our product or impose ongoing requirements for potentially costly post-approval studies or post-market

surveillance. For example, the holder of an approved BLA is obligated to monitor and report adverse events and

any failure of a product to meet the specifications in the BLA. The holder of an approved BLA must also submit

new or supplemental applications and obtain FDA approval for certain changes to the approved product, product

labeling or manufacturing process. Similar requirements apply to holders of (conditional) approvals in other

countries. Advertising and promotional materials must comply with FDA rules and are subject to FDA review, in

addition to other potentially applicable federal and state laws. In other countries outside of the United States,

advertising and promotional material may be subject to similar or more onerous rules. For example, direct-to-

consumer advertising of prescription medicinal products is prohibited in many jurisdictions outside of the United

States, including the European Union.

If we fail to comply with applicable regulatory requirements following approval of any of our product candidates, a

regulatory agency may:

–issue adverse public statements about our business or products;

–issue a warning letter asserting that we are in violation of the law;

–seek an injunction or impose civil or criminal penalties or monetary fines;

–suspend or withdraw regulatory approval or revoke a license;

–suspend any ongoing clinical studies;

–refuse to approve a pending BLA (or comparable approval) or supplements to a BLA (or comparable approval)

submitted by us;

–seize product; or

–refuse to allow us to enter into supply contracts, including government contracts.

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Any government investigation of alleged violations of law could require us to expend significant time and

resources in response and could generate negative publicity. The occurrence of any event or penalty described

above may inhibit our ability to commercialize any approved products and generate revenues.

If any of our products or product candidates cause undesirable side effects, it could delay or prevent their

regulatory approval, limit their commercial potential, or result in significant negative consequences following any

potential marketing approval. Products or product candidates we may develop may be associated with an

adverse immune response or other serious adverse events, undesirable side effects or unexpected

characteristics. In addition to serious adverse events or side effects caused by any of our products or product

candidates, the administration process or related procedures also can cause undesirable side effects. If any

such events occur, the clinical trials of any of our product candidates could be suspended or terminated.

If in the future we are unable to demonstrate that such adverse events were caused by factors other than our

product candidate, the FDA, the EMA or other regulatory authorities could order us to cease further development

of, or deny approval of, any of our product candidates for any or all targeted indications. Even if we are able to

demonstrate that all future serious adverse events are not product-related, such occurrences could affect patient

recruitment or the ability of enrolled trial participants to complete the trial. Moreover, if we elect, or are required,

to delay, suspend or terminate any clinical trial of any of our product candidates, the commercial prospects of

such product candidates, if approved, may be harmed and our ability to generate product sale revenues from

any of these product candidates may be delayed or eliminated. Any of these occurrences may harm our ability to

identify and develop product candidates, and may harm our business, financial condition, result of operations

and prospects significantly.

Additionally, following regulatory approval of a product candidate, the FDA or other regulatory authority could

require us to adopt a REMS or a risk management plan to ensure that the benefits of treatment with such

product candidate outweigh the risks for each potential patient, which may include, among other things, a

medication guide outlining the risks of the product for distribution to patients, a communication plan to health

care practitioners, extensive patient monitoring, or distribution systems and processes that are highly controlled,

restrictive, and more costly than what is typical for the industry.

Furthermore, if we or others later identify undesirable side effects caused by any product that we develop,

several potentially significant negative consequences could result, including:

–regulatory authorities may suspend or withdraw approvals or revoke licenses of such product;

–regulatory authorities may require additional warnings on the label;

–regulatory authorities may make unfavorable statements about the safety of our products;

–we may be required to change the way a product is administered or conduct additional clinical trials;

–we could be sued and held liable for harm caused to patients and their children; and

–our reputation may suffer.

Any of these events could prevent us from achieving or maintaining market acceptance of any products we may

identify and develop and could have a material adverse effect on our business, financial condition, results of

operations and prospects.

Upon the successful approval of a product candidate, we will continue to face significant regulatory oversight of

its manufacturing and distribution. Product manufacturers and their facilities are subject to payment of user fees

and continual review and periodic inspections by the FDA and other regulatory authorities for compliance with

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GMP and adherence to commitments made in the BLA or comparable approval. If we or a regulatory agency

discovers previously unknown problems with a product such as adverse events of unanticipated severity or

frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose

restrictions relative to that product or the manufacturing facility, including requiring recall or withdrawal of the

product from the market or suspension of manufacturing.

Governmental investigations and inquiries with respect to our COVID-19 vaccine and any other product

candidates for which we receive approval or emergency use authorization may adversely affect our

business, financial condition and results of operations.

In April 2025, we, along with several other pharmaceutical companies, received a letter from the Chairman of the

Permanent Subcommittee on Investigations of the U.S. Senate Homeland Security and Governmental Affairs

Committee, or the Subcommittee, that requested certain information and documents relating to the respective

COVID-19 vaccines we developed (in our case, Comirnaty). This and other governmental investigations or

inquiries in which we may become involved may result in additional claims and lawsuits being brought against us

by governmental agencies or private parties. It is not possible at this time to predict either the outcome or the

potential financial impact of the congressional investigation mentioned above or any further investigations or

inquiries of us that may result from such investigation. It is also not possible at this time to predict the additional

expenses related to such investigation, which may be significant. The initiation of any additional investigation

relating to us, the costs and expenses associated therewith, or any assertion, claim or finding of wrongdoing by

us, could:

–adversely affect our business, financial condition and results of operations;

–result in reputational harm and reduced market acceptance and demand for our products;

–harm our ability and our commercial partners’ ability to market our products;

–harm our ability to develop our product candidates;

–cause us to incur significant liabilities, costs and expenses; and

–cause our senior management to be distracted from execution of our business strategy.

Furthermore, the pending congressional investigation could negatively affect our ability to raise capital and

impair our ability to engage in strategic transactions.

We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false

claims laws, and other healthcare laws. If we are unable to comply, or have not fully complied, with such

laws, we could face substantial penalties.

We may be subject to additional healthcare regulation and enforcement by the U.S. federal government and by

authorities in the United States, the European Union and other jurisdictions in which we conduct our business.

Our operations may be directly, or indirectly through our prescribers, customers and purchasers, subject to

various federal and state fraud and abuse laws and regulations, including, without limitation, the federal Health

Care Program Anti-Kickback Statute, the federal civil and criminal False Claims Act, and the Physician Payments

Sunshine Act and regulations. Many states and other jurisdictions have similar laws and regulations, some of

which may be broader in scope. These laws will impact, among other things, our proposed sales, marketing and

educational programs. In addition, we may be subject to patient privacy laws enacted by both the federal

government and the states in which we conduct our business. The laws that will affect our operations include,

but are not limited to the following:

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–The U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from

knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe

or rebate), directly or indirectly, overtly or covertly, in cash or in kind, in return for the purchase,

recommendation, leasing or furnishing of an item or service reimbursable under a federal healthcare program,

such as the Medicare and Medicaid programs. This statute has been interpreted to apply to arrangements

between pharmaceutical manufacturers on the one hand, and prescribers, purchasers, and formulary

managers on the other. The ACA amends the intent requirement of the federal Anti-Kickback Statute to

provide that a person or entity no longer needs to have actual knowledge of this statute or specific intent to

violate it;

–The U.S. federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among

other things, individuals or entities from knowingly presenting, or causing to be presented, false or fraudulent

claims for payment or approval from Medicare, Medicaid or other government payors. The ACA provides, and

recent government cases against pharmaceutical and medical device manufacturers support, the view that

federal Anti-Kickback Statute violations and certain marketing practices, including off-label promotion, may

implicate the False Claims Act;

–The U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created new

federal criminal statutes that prohibit a person from knowingly and willfully executing a scheme or making

false or fraudulent statements to defraud any healthcare benefit program, regardless of the payor (e.g., public

or private);

–HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and their

implementing regulations, which imposes certain requirements relating to the privacy, security and

transmission of individually identifiable health information without appropriate authorization by entities subject

to the rule, such as health plans, health care clearinghouses and health care providers;

–The U.S. Federal Food, Drug, and Cosmetic Act, which prohibits, among other things, the adulteration or

misbranding of drugs, biologics and medical devices;

–The U.S. Public Health Service Act, which prohibits, among other things, the introduction into interstate

commerce of a biological product unless a biologics license is in effect for that product;

–Federal transparency laws, including the federal Physician Payment Sunshine Act, which require disclosure of

payments and other transfers of value provided to physicians and teaching hospitals, and ownership and

investment interests held by physicians and other healthcare providers and their immediate family members

and applicable group purchasing organizations;

–U.S. state law equivalents of each of the above federal laws, state laws that require drug manufacturers to

report information related to payments and other transfers of value to physicians and other healthcare

providers or marketing expenditures, and state laws governing the privacy and security of health information in

certain circumstances which are also applicable to us, and many of them differ from each other in significant

ways and may not have the same effect, thus complicating compliance efforts in certain circumstances;

–The U.S. Foreign Corrupt Practices Act of 1977, as amended, which prohibits, among other things, U.S.

companies and their employees and agents, as well as non-U.S. companies that are registered with the SEC,

from authorizing, promising, offering or providing, directly or indirectly, corrupt or improper payments or

anything else of value to foreign government officials, employees of public international organizations and

foreign government owned or affiliated entities, candidates for foreign political office, and foreign political

parties or officials thereof; and

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–Similar statutes, healthcare laws and regulations in the European Union and other jurisdictions, including

reporting requirements detailing interactions with and payments to healthcare providers.

Due to the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is

possible that some of our business activities could be subject to challenge under one or more of such laws. 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 ability to operate our

business and our results of operations.

The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation,

endorsement, purchase, supply, order or use of medicinal products is prohibited in the European Union. The

provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of European

Union member states and other jurisdictions, such as the U.K. Bribery Act 2010. Infringement of these laws

could result in substantial fines and imprisonment.

Payments made to physicians in certain EU member states must be publicly disclosed. Moreover, agreements

with physicians often must be the subject of prior notification and approval by the physician’s employer, his or

her competent professional organization or the regulatory authorities of the individual EU member states. These

requirements are provided in the national laws, industry codes, or professional codes of conduct, applicable in

the EU member states. Failure to comply with these requirements could result in reputational risk, public

reprimands, administrative penalties, fines or imprisonment.

We are subject to certain anti-corruption, anti-money laundering, export control, sanctions, and other

trade laws and regulations. We can face serious consequences for violations.

Among other matters, anti-corruption, anti-money laundering, export control, sanctions, and other trade laws and

regulations, which are collectively referred to as “trade laws,” prohibit companies and their employees, agents,

CROs, legal counsel, accountants, consultants, contractors and other collaborators from authorizing, promising,

offering, providing, soliciting, or receiving directly or indirectly, corrupt or improper payments or anything else of

value to or from recipients in the public or private sector. Violations of trade laws can result in substantial criminal

fines and civil penalties, imprisonment, the loss of trade privileges, debarment, tax reassessments, breach of

contract and fraud litigation, reputational harm, and other consequences. We have direct or indirect interactions

with officials and employees of government agencies or government-affiliated hospitals, universities and other

organizations. We plan to engage third parties for clinical trials and/or to obtain necessary permits, licenses,

intellectual property (including patents) and other regulatory approvals, and we can be held liable for the corrupt

or other illegal activities of our personnel, agents or collaborators, even if we do not explicitly authorize or have

prior knowledge of such activities.

We are subject to stringent privacy laws, information security policies and contractual obligations

governing the use, processing, and cross-border transfer of personal information and our data privacy

and security practices.

We receive, generate and store significant and increasing volumes of sensitive information, such as employee,

personal and patient data.

We are subject to a variety of local, state, national and international laws, directives and regulations that apply to

the collection, use, storage, retention, protection, disclosure, transfer and other processing of personal data,

collectively referred to as “data processing”, in the different jurisdictions in which we operate, including

comprehensive regulatory systems in the United States and Europe. Legal requirements relating to data

processing continue to evolve and may result in ever-increasing public scrutiny and escalating levels of

enforcement, sanctions and increased costs of compliance.

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Compliance with U.S. and international data protection laws and regulations could cause us to incur substantial

costs or require us to change our business practices and compliance procedures in a manner adverse to our

business. Moreover, complying with these various laws 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 and/or

adverse publicity and could negatively affect our operating results and business. 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, could result in adverse

publicity and could have a material adverse effect on our business, financial condition and results of operations.

The collection and use of personal data in the European Union had previously been governed by the provisions

of the EU Data Protection Directive, which EU member states were required to implement. While the Data

Protection Directive did not apply to organizations based outside the European Union, the GDPR has expanded

its reach to include any business, regardless of its location, that targets goods or services to residents in the

European Union or that “monitors” their behavior in the European Union. The GDPR imposes strict requirements

on controllers and processors of personal data, including special protections for “sensitive information” which

includes health and genetic information of patients residing in the European Union. The GDPR also imposes

strict rules on the transfer of personal data out of the European Union to the United States and other countries.

In addition, the GDPR provides that EU member states may make their own further laws and regulations limiting

the processing of personal data, including genetic, biometric or health data.

Since we are located in the European Union, we are subject to the GDPR. Additionally, as the GDPR applies

extraterritorially, we are also subject to the GDPR even where our data processing activities occur outside of the

European Union if such activities involve the personal data of individuals located in the European Union and the

above-mentioned applicable law triggers apply. GDPR regulations have imposed additional responsibility and

liability in relation to the personal data that we process and we may be required to put in place additional

mechanisms to ensure compliance with the new data protection rules. This may be onerous and may interrupt or

delay our development activities, and adversely affect our business, financial condition, results of operations and

prospects.

Other jurisdictions outside the European Union are similarly introducing or enhancing privacy and data security

laws, rules and regulations, which could increase our compliance costs and the risks associated with non-

compliance. In particular, in China, where some of our clinical data are originated, the cybersecurity, data

privacy, data protection, or other data-related laws and regulations, including the Personal Information Protection

Law, Regulations on Network Data Security Management, Provisions on Promoting and Regulating Cross-

Border Data Flows, and Human Genetic Resources Regulation (which regulates the collection and transfer

human biospecimens and genetic data derived from them in clinical research to foreign or foreign controlled

parties), may require approvals or filings prior to transferring those data to foreign-owned or controlled entities in

China or overseas, and these regimes are continually evolving, meaning their interpretation and enforcement

may be uncertain. These rules establish mechanisms such as governmental security assessment, certification,

and standard contractual clauses for certain cross‑border data transfers. Depending on the nature and volume of

data processed in China, we or our partners may be required to complete one or more of these transfer

mechanisms as a condition to exporting relevant data. Compliance with these requirements could affect our

operations, including data flows necessary for clinical development, manufacturing, or other activities conducted

in China. The scope and practical application of these rules continue to develop, and there is uncertainty

regarding how regulators will apply them in specific circumstances. In the United States, we may be subject to

restrictions and requirements under the Department of Justice’s Final Rule issued on December 27, 2024

implementing the Executive Order on Preventing Access to Americans’ Bulk Sensitive Personal Data and United

States Government-Related Data by Countries of Concern, signed on February 28, 2024. Practices regarding

the collection, use, storage, transmission and security of personal information by companies have also been

subject to increasing regulatory focus. As such, we cannot assure you that we will be compliant with such new

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regulations in all respects, and we may be ordered to rectify and terminate any actions that are deemed illegal by

the government authorities and become subject to fines and other government sanctions, which may materially

and adversely affect our business, financial condition, and results of operations. In addition, the uncertainties

regarding further interpretation and implementation of these laws and regulations may adversely affect the

secure storage of documented work as well as the cross-border transfer of important data and personal

information originated from our clinical trial activities, which are critical to the development of our pipelines.

We cannot guarantee that we are, or will be, in compliance with all applicable international regulations as they

are enforced now or as they evolve. For example, our privacy policies may be insufficient to protect any personal

information we collect, or may not comply with applicable laws, in which case we may be subject to regulatory

enforcement actions, lawsuits or reputational damage, all of which may adversely affect our business. There is

significant uncertainty related to the manner in which data protection authorities will seek to enforce compliance

with the GDPR and other international data protection regulations, especially with regard to clinical trial activities.

For example, it is not clear if the authorities will conduct random audits of companies doing business in the

European Union, or if the authorities will wait for complaints to be filed by individuals who claim their rights have

been violated, as enforcement practices vary from country to country. Enforcement uncertainty and the costs

associated with ensuring GDPR compliance may be onerous and adversely affect our business, financial

condition, results of operations and prospects. If we fail to comply with the GDPR and the applicable national

data protection laws of the EU member states, or if regulators assert we have failed to comply with these laws, it

may lead to regulatory enforcement actions, which can result in monetary penalties of up to €20,000,000 or up to

4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other

administrative penalties. If any of these events were to occur, our business and financial results could be

significantly disrupted and adversely affected.

Although we take measures to protect sensitive data from unauthorized access, use or disclosure, our

information technology and infrastructure may be vulnerable to attacks by hackers or viruses or breached due to

employee error, malfeasance or other malicious or inadvertent disruptions. Any such breach or interruption could

compromise our networks and the information stored there could be accessed by unauthorized parties,

manipulated, publicly disclosed, lost or stolen. Any such access, breach or other loss of information could result

in legal claims or proceedings, and liability under federal or state laws that protect the privacy of personal

information, as well as regulatory penalties. In many jurisdictions, there are legal requirements to provide notice

of breaches to affected individuals and/or regulators in certain circumstances. Such a notice could harm our

reputation and our ability to compete. Regulators may also have the discretion to impose penalties without

attempting to resolve violations through informal means. Although we have implemented security measures to

prevent unauthorized access to patient data, such data is currently accessible through multiple channels, and

there is no guarantee we can protect our data from breach. Unauthorized access, loss or dissemination could

also damage our reputation or disrupt our operations, including our ability to conduct our analyses, deliver test

results, process claims and appeals, provide customer assistance, conduct research and development activities,

collect, process and prepare company financial information, provide information about our tests and other patient

and physician education and outreach efforts through our website, and manage the administrative aspects of our

business.

If we or our third-party suppliers fail to comply with environmental, health and safety laws and

regulations, we could become subject to fines or penalties or incur costs that could harm our business.

We are 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. Our operations involve the use of hazardous and flammable materials, including chemicals and

biological materials. Our operations also may produce hazardous waste products. We generally anticipate

contracting with third parties for the disposal of these materials and wastes. We will not be able to eliminate the

risk of contamination or injury from these materials. In the event of contamination or injury resulting from any use

by us of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed

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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.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to

injuries to our employees resulting from the use of hazardous materials, this insurance may not provide

adequate coverage against potential liabilities.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and

safety laws and regulations. These current or future laws and regulations may impair our research, development

or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines,

penalties or other sanctions.

Our business operations and current and future relationships with investigators, healthcare

professionals, consultants, third-party payors, patient organizations and customers will be subject to

applicable healthcare regulatory laws, which could expose us to penalties.

Our business operations and current and future arrangements with investigators, healthcare professionals,

consultants, third-party payors, patient organizations and customers, may expose us to broadly applicable fraud

and abuse and other healthcare laws and regulations. These laws may constrain the business or financial

arrangements and relationships through which we conduct our operations, including how we research, market,

sell and distribute our product candidates, if approved.

Ensuring that our internal operations and future business arrangements with third parties comply with applicable

healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will

conclude that our business practices do not comply with current or future statutes, regulations, agency guidance

or case law involving applicable fraud and abuse or other healthcare laws and regulations.

If any of the physicians or other providers or entities with whom we expect to do business are found to not be in

compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including

exclusions from government-funded healthcare programs and imprisonment, which could affect our ability to

operate our business. Further, defending against any such actions can be costly and time-consuming and may

require significant personnel resources. Therefore, even if we are successful in defending against any such

actions that may be brought against us, our business may be impaired.

Risks Related to Ownership of the ADSs

We have experienced and may continue to experience significant volatility in the market price of the

ADSs representing our ordinary shares.

Biopharmaceutical companies such as BioNTech SE that are developing potential therapeutics and vaccines to

combat COVID-19, as well as conducting mRNA-based research in oncology and infectious disease more

generally, have experienced significant volatility in the price of their securities upon publication of preclinical and

clinical data as well as news about their development programs and commercialization activities. For example,

during 2025, the closing sales price of the ADSs representing our ordinary shares on the Nasdaq Global Select

Market ranged from $86.65 to $126.88. In addition, volatility in the overall market and in the market price of a

particular company’s securities can result in securities litigation, including shareholder class action lawsuits. Any

securities litigation can result in substantial costs and a diversion of our management’s attention and resources.

Acquisitions, joint ventures and collaborations may increase our capital requirements, dilute our

shareholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks. We

may not realize the benefits of these acquisitions, joint ventures or collaborations.

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We may evaluate various acquisitions and collaborations, including licensing or acquiring complementary

products, intellectual property rights, technologies or businesses. Any potential acquisition, joint venture or

collaboration may entail numerous risks, including:

–increased operating expenses and cash requirements;

–the assumption of additional indebtedness or contingent liabilities;

–assimilation of operations, intellectual property and products of an acquired company, including difficulties

associated with integrating new personnel;

–the diversion of our management’s attention from our existing product programs and initiatives in pursuing

such a strategic merger or acquisition;

–retention of key employees, the loss of key personnel, and uncertainties in our ability to maintain key business

relationships;

–risks and uncertainties associated with the other party to such a transaction, including the prospects of that

party and their existing products or product candidates and regulatory approvals, their quality control, quality

assurance, internal controls, legal and compliance procedures; and

–our inability to generate revenue from acquired technology or products sufficient to meet our objectives in

undertaking the acquisition or even to offset the associated acquisition and maintenance costs.

In addition, if we undertake acquisitions, we may utilize our cash, issue dilutive securities, assume or incur debt

obligations, incur large one-time expenses and acquire intangible assets that could result in significant future

amortization expense. For example, in July 2023, we acquired InstaDeep, a leading global technology company

in the field of AI and machine learning, for upfront consideration of cash and BioNTech shares, and potential

future milestone payments. Although we believe that AI and machine learning technology has the potential to

accelerate the development of therapeutic programs and further optimize manufacturing and supply chain

processes, it is possible that our use of the acquired technology will not achieve the desired results, and that we

will not be able to retain and grow InstaDeep’s business around the world. If demand for the services developed

by InstaDeep does not continue, or if we are unable to improve our AI and machine learning technology in a

timely, effective and competitive manner, we may not be able realize the expected outcomes from the InstaDeep

acquisition. In January 2025, we acquired Biotheus, a clinical-stage biotechnology company, for upfront

consideration predominantly of cash, with a small portion in our ADSs, and potential future milestone payments.

Although the Biotheus acquisition expands our operations in China, our expectations regarding the creation of

long-term value for shareholders and potential future commercialization in oncology may not be realized. In

December 2025, we acquired CureVac N.V., a biotechnology company focused on the development of mRNA

therapeutics, through a public exchange offer. While we believe the acquisition has the potential to enhance our

capabilities in mRNA research, development, manufacturing and commercialization, there can be no assurance

that we will realize the anticipated benefits from the transaction. There is no guarantee that we will realize any

anticipated benefits of these or future acquisitions, or that the diversification of our business through acquired

technology or products will be successful.

Moreover, we may not be able to locate suitable acquisition or collaboration opportunities and this inability could

impair our ability to grow or obtain access to technology or products that may be important to the development of

our business.

Following the acquisition of CureVac, we may be required to repay monies received under the Advance

Purchase Agreement with the European Commission for its first-generation COVID-19 vaccine

candidate.

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On November 30, 2020, prior to our acquisition of CureVac, CureVac AG entered into an Advance Purchase

Agreement, which we refer to as the APA, with the EU Commission, acting on behalf of all Member States of the

European Union, for the supply of up to 405 million doses of its first-generation COVID-19 vaccine candidate,

which we refer to as CVnCoV. Under the APA, CureVac AG received an upfront payment of €450 million for

development and commercial supply activities of CVnCoV. In October 2021, CureVac AG notified the EU

Commission of the withdrawal of its regulatory approval application for CVnCoV, which notification automatically

terminated the APA. According to the APA, in such case of termination, CureVac AG would be required to return

any unspent amount of the upfront payment. In the context of the APA, “spent” means either costs incurred, or

commitments made in connection with the purposes set forth in the APA.

On July 24, 2024, the EU Commission informed CureVac SE that it had engaged Deloitte, S.L., which we refer to

as Deloitte, to conduct an audit of CureVac SE’s compliance with the APA. On September 17, 2025, the EU

Commission provided CureVac SE with Deloitte’s draft audit report, which included preliminary findings alleging

missing documentation, absence of project cost allocation, cost traceability and reconciliations, as well as

inconsistencies between information submitted during the audit and financial information previously provided to

the EU Commission. CureVac SE is cooperating fully with the EU Commission and Deloitte and submitted a

detailed response and objections on October 17, 2025. The EU Commission subsequently issued its final audit

report.

CureVac SE contested the findings in Deloitte’s draft audit report and believes it can refute the issues raised.

However, it remains uncertain to what extent Deloitte and the EU Commission will accept CureVac SE’s position.

It is also unclear whether the EU Commission will rely on Deloitte’s final audit report to seek recovery of any

portion or all of the €450 million upfront payment. As the successor to CureVac following the acquisition, we

cannot exclude the possibility of being required to repay a portion or all of the €450 million upfront payment.

Should we be unsuccessful in contesting any such repayment claims, or the payment of related fines, this could

materially affect our financial position, cash flows, and results of operations.

Our Articles of Association designate specific courts in the United States as the exclusive forum for

certain U.S. litigation that may be initiated by our shareholders, which could limit our shareholders’

ability to obtain a favorable judicial forum for disputes with us.

Our Articles of Association provide that the United States District Court for the Southern District of New York shall

be the competent court of jurisdiction for the resolution of any litigation on the grounds of or in connection with

U.S. federal or state capital market laws. In the absence of these provisions, under the Securities Act of 1933, as

amended, or the Securities Act, U.S. federal and state courts have been found to have concurrent jurisdiction

over suits brought to enforce duties or liabilities created by the Securities Act.

The choice of forum provision contained in our Articles of Association may limit a shareholder’s ability to bring a

claim in a judicial forum that it finds favorable for disputes with us or our executive officers, directors, or other

employees, or impose additional litigation costs on shareholders in pursuing any such claims, particularly if the

shareholders do not reside in or near the state of New York, which may discourage such lawsuits. In addition,

while the Delaware Supreme Court ruled in March 2020 that federal forum selection provisions purporting to

require claims under the Securities Act be brought in federal court are “facially valid” under Delaware law, there

is uncertainty as to whether other U.S. or German courts will enforce our choice of forum provision. The

enforceability of similar choice of forum provisions in other companies’ governing documents has been

challenged in recent legal proceedings, and it is possible that a court in the relevant jurisdictions with respect to

us could find the choice of forum provision contained our Articles of Association to be inapplicable or

unenforceable. If the relevant court were to find the choice of forum provision contained in our articles of

association to be inapplicable or unenforceable, we may incur additional costs associated with resolving such

matters in other jurisdictions, which could adversely affect our business, financial condition and operating results.

The choice of forum provision may also impose additional litigation costs on shareholders who assert that the

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provision is not enforceable or invalid. The United States District Court for the Southern District of New York may

also reach different judgments or results than would other courts, including courts where a shareholder

considering a U.S.-based action may be located or would otherwise choose to bring the action, and such

judgments may be more or less favorable to us than our shareholders.

Holders of the ADSs may not be able to participate in any future preemptive subscription rights issues

or elect to receive dividends in shares, which may cause additional dilution to their holdings.

Under German law, the existing shareholders of a company generally have a preemptive right in proportion to

the amount of shares they hold in connection with any issuance of ordinary shares, convertible bonds, bonds

with warrants, profit participation rights and participating bonds. However, our shareholders in a shareholders’

meeting may vote, by a majority representing at least three-quarters of the share capital represented at the

meeting, to waive this preemptive right provided that, from the company’s perspective, there exists good and

objective cause for such waiver.

The deposit agreement provides that the depositary need not make rights available to you unless the distribution

to ADS holders of both the rights and any related securities are either registered under the Securities Act or

exempted from registration under the Securities Act. We are under no obligation to file a registration statement

with respect to any such rights or securities or to endeavor to cause such a registration statement to be declared

effective. Moreover, we may not be able to establish an exemption from registration under the Securities Act.

Accordingly, ADS holders may be unable to participate in our future rights offerings and may experience dilution

in their holdings. For example, ADS holders were unable to participate in our summer 2020 rights offering. In

addition, if the depositary is unable to sell rights that are not exercised or not distributed or if the sale is not lawful

or reasonably practicable, it will allow the rights to lapse, in which case you will receive no value for these rights.

The amount and frequency of our dividends and ADS repurchases may fluctuate.

The amount, timing and execution of any ADS repurchase program we conduct in the future and the amount and

timing of any dividends we pay may fluctuate based on our priorities for the use of cash for other purposes, and

any ADS repurchases would be subject to the parameters contained in the applicable repurchase plan. These

purposes may include operational spending, capital spending, acquisitions and repayment of debt. Additionally,

we may choose to repurchase ADSs so that such ADSs may be used to settle outstanding and future equity

awards granted to our employees. Changes in cash flows, tax laws and the price of the ADSs could also impact

any ADS repurchase program. Additionally, we may enter into a Rule 10b5-1 trading plan governing the

repurchases, and if we do, we would have no discretion over the particular purchases made and would only be

able to set minimum price floors and maximum ADS count ceilings.

Our principal shareholders and management own a significant percentage of our ordinary shares and

will be able to exert significant control over matters subject to shareholder approval.

Our executive officers, directors, five percent shareholders, and their affiliates beneficially own a majority of our

ordinary shares (including ordinary shares represented by ADSs) as of December 31, 2025, and will have the

ability to influence us through their ownership positions. For example, these shareholders, acting together, may

be able to exert significant influence over matters such as elections of directors, amendments of our

organizational documents, or approval of any merger, sale of assets or other major corporate transaction. This

may prevent or discourage unsolicited acquisition proposals or offers for our ordinary shares that shareholders

may believe are in their best interest. Such insiders may also act in concert to waive rights to participate in rights

offerings, as was done in our summer 2020 rights offering, which would have the effect of permitting the ADSs or

shares underlying such waived rights to be offered to the public in an underwritten offering without contravening

German law pricing requirements.

The large number of shares eligible for sale or subject to rights requiring us to register them for sale

could cause the market price of the ADSs to drop significantly, even if our business is performing well.

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We have filed registration statements on Form S-8 under the Securities Act to register all ordinary shares issued

or issuable under our equity plans. Such Form S-8 registration statements have become, and any other

registration statements on Form S-8 we file in the future will become, effective upon filing, upon which shares

registered under such registration statements become available for sale in the open market.

Additionally, certain sales of ADSs or our ordinary shares that we have made have included, and we may in the

future make sales including, holding period restrictions or registration rights. Sales of ADSs or our ordinary

shares as restrictions end or pursuant to registration rights may make it more difficult for us to finance our

operations through the sale of equity securities in the future at a time and at a price that we deem appropriate.

These sales also could cause the trading price of the ADSs to fall and make it more difficult to sell the ADSs on

favorable terms.

If we are a “passive foreign investment company” for U.S. federal income tax purposes, there may be

adverse U.S. federal income tax consequences to U.S. investors.

Based on our income and assets, we believe that we should be treated as a “passive foreign investment

company,” or PFIC, for the preceding taxable year. However, the determination of our PFIC status is made

annually based on the factual tests described below. Consequently, while we may be a PFIC in future years, we

cannot estimate with certainty at this stage whether or not we are likely to be treated as a PFIC in the current

taxable year or any future taxable years. Generally, if, for any taxable year, at least 75 percent of our gross

income is “passive income” or at least 50 percent of our gross assets during the taxable year (based on the

average of the fair market values of the assets determined at the end of each quarterly period) are assets that

produce or are held for the production of passive income, we will be characterized as a PFIC for U.S. federal

income tax purposes. Passive income for this purpose generally includes, among other things, dividends,

interest, rents, royalties, gains from commodities and securities transactions, and gains from assets that produce

passive income. However, rents and royalties received from unrelated parties in connection with the active

conduct of a trade or business should not be considered passive income for purposes of the PFIC test. For

example, if we were to be characterized as a PFIC for U.S. federal income tax purposes in any taxable year

during which a U.S. Holder (as defined in “Taxation —Material United States federal income tax considerations”

in this Annual Report) holds ordinary shares or ADSs, such U.S. Holder could be subject to additional taxes and

interest charges upon certain distributions by us and any gain recognized on a sale, exchange or other

disposition of our shares, whether or not we continue to be characterized as a PFIC. Certain adverse

consequences of PFIC status can be mitigated if a U.S. Holder makes a “mark to market” election or a “Qualified

Electing Fund,” or QEF, election. We have made available to U.S. Holders the information necessary to make

and maintain a QEF election for the year ended December 31, 2024, and intend to provide U.S. holders with the

necessary information for any taxable year in which we are treated as a PFIC. See “Taxation —Material United

States federal income tax considerations —Passive foreign investment company considerations” in this Annual

Report.

Whether we are a PFIC for any taxable year will depend on the composition of our income and the composition

and value of our assets from time to time. Each U.S. Holder is strongly urged to consult their tax advisor

regarding these issues and any available elections to mitigate such tax consequences.

The acquisition of a substantial interest in the Company by non-EU/non-EFTA investors requires

government approval, which may restrict certain investments and limit demand for the BioNTech ADSs.

As the Company is considered an operator of “critical infrastructure” within the meaning of the Ordinance on the

Designation of Critical Infrastructure pursuant to the BSI Act (Verordnung zur Bestimmung Kritischer

Infrastrukturen nach dem BSI-Gesetz), it falls within the scope of the cross-sector review of the German foreign

investment screening regime under the German Foreign Trade and Payments Ordinance

(Außenwirtschaftsverordnung). As a result, non-EU/non-EFTA investors intending to acquire, directly or indirectly,

at least 10% of the voting rights in the Company or who already hold voting rights in the Company and will

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acquire further voting rights reaching or exceeding 20%, 25%, 40%, 50% or 75% of the voting rights in the

Company must notify the planned acquisition to the German Federal Ministry for Economic Affairs and Energy

(Bundesministerium für Wirtschaft und Energie, or the BMWE). The BMWE will then assess whether the

acquisition likely adversely affects the public order or security of Germany or other EU member states or projects

or programs of Union interest within the meaning of Article 8 of Regulation (EU) 2019/452 of the European

Parliament and of the Council of 19 March 2019 establishing a framework for the screening of foreign direct

investments into the Union. Clearance by the BMWE qualifies as a closing condition for all over-the-counter

transactions. If the acquisition has been made via the stock exchange, the acquirer is prohibited from exercising

its voting rights until the transaction has been cleared or is deemed cleared. If the BMWE identifies likely

adverse effects, the acquisition of voting rights in the Company could be restricted or prohibited or, if the

acquisition has been made via the stock exchange, the BMWE may order a sell-down of the voting rights in the

Company acquired via the stock exchange or a transfer to a trustee within a certain period of time and/or prohibit

the exercise of voting rights until such time as the acquisition is finally reversed.

Item 4. Information on the Company

A. History and Development of the Company

We are committed to improving the health of people worldwide with our fundamental research and development

of immunotherapies. Scientific rigor, innovation and passion are our driving forces. BioNTech was founded by

scientists and physicians to translate science into survival by combining fundamental research and operational

excellence.

We were founded and incorporated on June 2, 2008 as Petersberg 91, V AG, a German stock corporation

(Aktiengesellschaft). We changed our name to BioNTech AG on December 11, 2008. On March 8, 2019, we

converted to a European stock corporation (Societas Europaea, or SE) under the laws of Germany and the

European Union called BioNTech SE. We completed our initial public offering in October 2019. ADSs

representing our ordinary shares are currently listed on the Nasdaq Global Select Market under the symbol

“BNTX”.

Our principal executive offices are located at An der Goldgrube 12, D-55131 Mainz, Germany. Our telephone

number is +49 6131-9084-0. Our website address is www.biontech.com. The information contained on, or that

can be accessed through, our website is not part of this document. Our agent for service of process solely for the

purpose of notices and communications from the SEC in the United States is c/o BioNTech US Inc., 40 Erie

Street, Suite 110, Cambridge, Massachusetts 02139, +1 (617) 337-4701. The SEC maintains an Internet site

that contains reports, proxy and information statements, and other information regarding issuers that file

electronically with the SEC at http://www.sec.gov.

For information on our principal capital expenditures and divestitures, see Item 5 of this Annual Report.

B. Business Overview

I. Overview

We are a global next-generation immunotherapy company aiming to pioneer novel medicines against cancer,

infectious diseases and other serious diseases. Since our founding in 2008, we have focused on harnessing the

power of the immune system to address human diseases with unmet medical needs and major global health

burdens. Our fully integrated model combines decades of research in immunology with a multi-technology

innovation engine, GMP manufacturing, translational drug discovery, clinical development, commercial

capabilities, computational medicine, data science and artificial intelligence, or AI, and machine learning, or ML,

capabilities to discover, develop and commercialize our marketed product and product candidates.

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We have built a broad toolkit across multiple technology platforms, including a diverse range of potentially first-

in-class therapeutic approaches. This includes investigational messenger ribonucleic acid, or mRNA

immunotherapies and protein-based therapeutics (including targeted antibodies such as monoclonal, bispecific

and antibody-drug conjugates, or ADCs).

Our multi-technology combination of platforms and product candidates aims to position us as pioneers in the

field of individualized, patient-centric therapeutic approaches in oncology and infectious diseases. We believe

that by combining complementary treatment modalities, we can leverage the potential of each technology to

provide precise and personalized treatments to patients. Such treatments, if approved, could both increase the

likelihood of therapeutic success and reduce the risk of therapeutic resistance.

Our primary focus is oncology, where we endeavor to address the full continuum of cancer from early to late

disease stages. The root causes of cancer treatment failure are cancer heterogeneity and interindividual

variability. Driven by random sequential mutations, every patient’s cancer is different and within one patient’s

tumor, every cell is different. Addressing these two challenges is the core of our strategy. To augment anti-tumor

activity and to counteract resistance mechanisms, we seek to combine compounds with non-overlapping,

potentially synergistic mechanisms of action.

In infectious diseases, our goal is to develop vaccines and therapeutics caused by respiratory viruses, latent

viruses, bacteria and parasites. We believe our scientific approach and our mRNA technology have the potential

to significantly contribute to the fight against global health threats caused by infectious diseases. We have

pursued both strategic partnerships and corporate collaborations to partially fund our infectious disease global

health programs and aim to continue to do so. Our infectious disease programs aim to contribute to equitable

access to innovative vaccines for high medical need indications.

Our approach has generated a robust and diversified product candidate pipeline across a range of technologies

in oncology and infectious disease, and has led to the approval of our first marketed pharmaceutical product,

Comirnaty. Innovation is at the core of our company, and we see potential for our technologies to expand beyond

oncology and infectious diseases.

II. Execution of BioNTech’s Strategy

In 2025, we made important progress across key strategic areas of the company to strengthen our technology

platforms, capabilities and infrastructure, through strategic investments, acquisitions and partnerships impacting

patients, shareholders and other stakeholders.

1. Advanced Oncology Pipeline

We continued to develop our innovative oncology pipeline. In 2025, we started multiple clinical trials and brought

several assets into mid- and late-stage development, namely Phase 2 and Phase 3 clinical trials, across a range

of technologies and indications. Today, our pipeline consists of 16 clinical programs in oncology, with more than

25 Phase 2 and Phase 3 clinical trials and 10 novel combination trials ongoing with our investigational bispecific

antibody pumitamig. In 2025, we and our partners reported data across our portfolio at multiple medical

meetings and published manuscripts in peer reviewed journals.

2. COVID-19 Vaccine Market Leadership

We continued to build our COVID-19 vaccine franchise and maintained market leadership in multiple key

geographies. In 2025, we and Pfizer successfully launched our SARS-CoV-2 variant-adapted vaccine for the

2025/2026 vaccination season in 69 markets globally. We maintained our leadership position in the global

COVID-19 vaccine market, achieving a market share of over 50% during the fall 2025 vaccination season.

3. Strategic Transactions and Partnerships

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In February 2025, we announced the completion of our acquisition of Biotheus. With the acquisition, we obtained

full global rights to the late-stage clinical asset pumitamig. In June 2025, we entered into a global co-

development and co-commercialization agreement with Bristol Myers Squibb Company, or Bristol Myers Squibb,

to jointly develop, manufacture and commercialize pumitamig across numerous solid tumor types. The

collaboration leverages both partners’ expertise, resources and global footprint to accelerate pumitamig’s path

towards potential regulatory approvals and market launches

In December 2025, we announced our acquisition of CureVac N.V., or CureVac. The strategic transaction

complements BioNTech’s capabilities and proprietary technologies in mRNA design and delivery formulations.

4. Maintained Strong Financial Position

In 2025, we maintained a strong balance sheet through disciplined financial performance, ending the year with

approximately €17.2 billion in total cash, cash equivalents and security investments. With a strong financial

position, leading COVID-19 vaccine franchise and innovative oncology and infectious disease pipeline, we

believe we are well positioned to continue executing our vision of pioneering novel medicines against cancer,

infectious diseases and other serious diseases.

On March 10, 2026, we announced plans for an independent company to be established and led by BioNTech

co-founders Prof. Ugur Sahin, M.D., and Prof. Özlem Türeci, M.D. The new company with distinct resources,

operations and funding options, will advance next-generation mRNA innovations. We plan to contribute related

rights and mRNA technologies to the new company to enable and support the prioritized development of next-

generation mRNA innovations with disruptive potential. With both companies focusing on their respective

strategic priorities, we expect to maximize value for patients and shareholders alike. Our CEO and CMO will

transition into the management of their new company by the end of 2026 after their current service agreements

end. Our Supervisory Board has initiated an executive search to identify successors for the positions to ensure a

smooth transition and seamless execution of our strategy.

III. Company Evolution

We are committed to translating science into survival for patients by advancing BioNTech’s strategy and

executing it to become a global immunotherapy powerhouse with multiple approved products and revenue

streams.

As part of this continued approach, we have built a unique pipeline that includes technologies and candidates

with disruptive potential. In oncology, we focus on potentially synergistic therapeutic approaches, including

innovative immunomodulators, targeted therapies, and mRNA cancer immunotherapies. We plan to continue to

significantly invest in their broad clinical evaluation across multiple cancer indications with significant (unmet)

medical needs, as well as their commercialization in key markets. We aim to further enhance the therapeutic

profile of our investigational therapies through the evaluation of novel-novel combinations, including our

differentiated portfolio targeted therapy candidates such as ADCs.

As we continue to invest in executing our vision, we remain committed to cost-effective value generation. We

actively manage our whole pipeline and assess all sites across BioNTech, including newly acquired assets,

according to key criteria: strategic alignment, operational efficiency, and sustainable value creation. For 2026, we

consequently plan to continue to significantly invest in essential areas while optimizing capacities in others.

The consolidation and adjustment of capacities announced in 2025 are ongoing and are expected to span

through 2027. We currently expect that this will involve consolidating and adjusting capacities within our

manufacturing network. We will continue to drive progress with a focus on our highest potential opportunities and

we believe we are well-positioned to continue advancing our strategic vision. We look forward to another year of

meaningful progress building on our achievements in 2025.

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IV. Marketed Products: Comirnaty, our COVID-19 Vaccine Program (BNT162)

COVID-19 vaccination has played an important role in saving lives and livelihoods across the world. Our

commercial product, developed in 2020, Comirnaty, was the first-ever approved mRNA-based product, and, to

our knowledge, remains the fastest ever developed prophylactic vaccine from viral sampling to approval. As of

March 2026, our COVID-19 vaccine products have been authorized or approved for emergency or temporary

use or granted marketing authorization in more than 180 countries and regions worldwide. Our efforts have

resulted in over 5 billion doses shipped globally.

Under our collaboration with Pfizer, we are the Marketing Authorization Holder in the United States, the

European Union, or EU, the UK, Canada and other countries. Additionally, we are the holder of emergency use

authorizations or equivalents in the United States (jointly with Pfizer) and other countries for the COVID-19

vaccine program. Pfizer has marketing and distribution rights worldwide apart from Greater China, Germany, and

Türkiye. We have the marketing and distribution rights to Comirnaty in Germany and Türkiye.

Under our collaboration with Fosun Pharmaceutical Industrial Development, Co., Ltd, or Fosun Pharma, Fosun

Pharma has marketing and distribution rights in Mainland China, Hong Kong Special Administrative Region, or

SAR, Macau SAR and Taiwan region.

1. Commercial, Manufacturing and Distribution Updates

We expect that as SARS-CoV-2 continues to evolve, and the risk of severe COVID-19 disease and deaths

persists, there will be continued demand for primary and seasonal vaccinations, especially for at-risk and

immunocompromised populations. Studies have demonstrated that natural immunity acquired by SARS-CoV-2

infection is variable across individuals and wanes over time due to viral escape mutations and decreasing

antibody titers. The risk of severe COVID-19 disease remains high in vulnerable populations. Vaccination not

only reduces the risk of severe COVID-19 but may also mitigate the risk of health impairments related to

COVID-19. Given this, and our current understanding of COVID-19’s burden on healthcare systems during the

fall and winter season, along with its observed peaks at other times of the year, we anticipate the need for

annual adapted vaccines to be a long-term component of COVID-19 vaccination practices.

In 2025, we and Pfizer continued our global COVID-19 vaccine leadership with the commercial launch of our

SARS-CoV-2 variant-adapted vaccine for the 2025/2026 vaccination season. Since the declaration of the

pandemic, we have developed and commercialized multiple COVID-19 vaccine products, including our most

recently developed COVID-19 vaccine targeting the LP.8.1 strain. Each is referred to as Comirnaty.

In 2025, we continued transitioning from an advanced purchase agreement framework to commercial market

ordering in some geographies.

We and Pfizer have an ongoing COVID-19 Vaccine Purchase Agreement with the European Commission, or the

EC, to deliver COVID-19 vaccines to the EU. The agreement reflects our and Pfizer’s commitment to working

collaboratively to help address ongoing public health needs. The 2023 agreement rephased delivery of doses

annually through 2026. In addition, the agreement includes an aggregate volume reduction, providing additional

flexibility for EU Member States. The EC will maintain access to future adapted COVID-19 vaccines and the

ability to donate doses.

We and Pfizer have established an efficient and robust global vaccine supply chain and manufacturing network

capable of meeting global demand.

More details on our manufacturing operations and facilities can be found in “VII. Manufacturing.”

2. Clinical Development and Regulatory Updates

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While JN.1 and KP.2 variant-adapted vaccines provided some protection against a range of outcomes from JN.1-

lineage related COVID-19 disease, evidence suggests that vaccines better matched to currently circulating

SARS-CoV-2 sublineages may provide improved protection against symptomatic and severe COVID-19 disease.

–In May 2025, the WHO, EMA and FDA each issued recommendations to update the antigenic composition of

authorized COVID-19 vaccines for the 2025-2026 vaccination season. The WHO advised manufacturers that

monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens and that monovalent LP.8.1 is a

suitable alternative vaccine antigen. The EMA recommended that marketing authorization holders adapt

vaccines to target the LP.8.1 variant of the JN.1 family of Omicron subvariants, and vaccines targeting JN.1 or

KP.2 strains could be considered for the vaccination campaigns in 2025 until the updated LP.8.1 vaccines

become available. The FDA advised manufacturers that COVID-19 vaccines for use in the United States in the

fall of 2025 should be a monovalent JN.1-lineage-based composition, preferentially targeting the LP.8.1 strain.

–In July 2025, the EMA’s Committee for Medicinal Products for Human Use, or CHMP, recommended

marketing authorization for the companies’ LP.8.1-adapted monovalent COVID-19 vaccine. In August 2025,

following authorization by the EC, the new variant-adapted COVID-19 vaccine was made available for

shipment to applicable EU member states.

–In August 2025, the FDA approved the supplemental Biologics License Application for our and Pfizer’s LP.8.1-

adapted monovalent COVID-19 vaccine for use in adults aged 65 years and older, as well as in individuals

aged five through 64 years with at least one underlying condition that puts them at high risk for severe

outcomes from COVID-19. The new variant-adapted COVID-19 vaccine was shipped promptly following

approval and was made available in pharmacies, hospitals, and clinics across the United States.

Ahead of the 2025-2026 COVID-19 vaccination season, we initiated a Phase 3 (NCT07069309) study to

investigate the safety, tolerability, and immunogenicity of our LP.8.1-adapted COVID-19 vaccine in adults 65 and

older and adults aged 18 through 64 with at least one underlying risk condition for severe COVID-19. In

September 2025, we announced positive topline results from the Phase 3 trial. The preliminary data show a

robust increase in neutralizing antibodies targeting the LP.8.1 sublineage of SARS-CoV-2 following vaccination.

The safety profile of the vaccine was consistent with previous studies, with no new safety concerns identified.

Three post-marketing commitment clinical trials are ongoing, with a fourth planned.

We and Pfizer intend to continue to monitor the evolving epidemiology of COVID-19 and remain prepared to

develop modified vaccine formulas as the data support and as regulatory agencies recommend.

V. Pipeline of Product Candidates

Below is a summary of active clinical trials evaluating our product and clinical product candidates, organized by

platform and indication.

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Oncology1,2


Phase 1	Phase 1/2		Phase 2			Phase 2/3	Phase 3
BNT116 Adv. NSCLC	BNT324/DB-13115 Multiple solid tumors	Pumitamig3 + BNT3213 1L HCC4,11	Autogene cevumeran6 Adj. CRC	Pumitamig3 2L ES-SCLC11	Pumitamig3 or BNT325/DB-13055 + BNT324/DB-13115 Multiple solid tumors4	BNT113 1L HPV16+ HNSCC	Gotistobart7 Met. NSCLC
BNT211 Multiple solid tumors	BNT325/DB-13055 Multiple solid tumors	Pumitamig3 + BNT324/DB-13115 Adv./met. NSCLC and SCLC4	Autogene cevumeran6 Adj. PDAC	Pumitamig3 2L+ EGFRm NSCLC11		Pumitamig3 1L met. CRC	Pumitamig3 1L ES-SCLC
BNT314/GEN10599 Multiple solid tumors	BNT329 Multiple solid tumors	Pumitamig3 + BNT325/DB-13055 Multiple solid tumors4	BNT11610 1L adv. NSCLC	Pumitamig3 2L Glioblastoma11		Pumitamig3 1L NSCLC	Pumitamig3 2L SCLC11
BNT317 Multiple solid tumors	Gotistobart7 Met. CRPC	Pumitamig3 + BNT326/YL2028 Multiple solid tumors	BNT326/YL2028 Multiple solid tumors11	Pumitamig3 1L HCC11			Pumitamig3 1L adv./met.TNBC11
BNT326/YL2028 Multiple solid tumors	Gotistobart7 Multiple solid tumors	Pumitamig3 + BNT326/YL2028 Adv. NSCLC	BNT326/YL2028 Adv./met. BC.11	Pumitamig3 1L MPM11			Trastuzumab pamirtecan5 Met. BC
	Pumitamig3 Multiple solid tumors	Pumitamig3 + Trastuzumab pamirtecan5 Adv./met. BC4	Gotistobart7 PROC	Pumitamig3 2L NEN11			Trastuzumab pamirtecan5 2L EC
	Pumitamig3 1L adv./met. TNBC11	Trastuzumab pamirtecan5 Multiple solid tumors	Pumitamig3 1L met. CRC11	Pumitamig3 2L adv./met. NSCLC
	Pumitamig3 + BNT314/GEN10599 Met. CRC4		Pumitamig3 1L ES-SCLC11	Pumitamig3 1L met. PDAC11
	Pumitamig3 + BNT3212 Multiple solid tumors		Pumitamig3 1L/2L+ ES-SCLC	Pumitamig3 1L/2L adv./met. TNBC


Next generation immunomodulator			Targeted therapy			mRNA cancer immunotherapy			Novel-novel combination

Infectious Diseases1,2


Phase 1	Phase 1/2	Phase 2	Commercial
BNT16312 HSV	BNT162 + BNT16113 COVID-19 - Influenza combination	BNT16616 Mpox	BNT16213,14 COVID-19
BNT351 HIV	BNT16415 Tuberculosis
	BNT165 Malaria
	BNT16616 Mpox


Antibody			mRNA

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(1)For further details about BioNTech’s rights, see elsewhere in this Annual Report.

(2)Abbreviations are defined in the corresponding trial descriptions.

(3)Partnered with Bristol Myers Squibb.

(4)Trial is currently being conducted by or on behalf of BioNTech. Bristol Myers Squibb holds co-exclusive rights to pumitamig.

(5)Partnered with DualityBio.

(6)Partnered with Genentech, a member of the Roche Group.

(7)Partnered with OncoC4.

(8)Partnered with MediLink Therapeutics.

(9)Partnered with Genmab.

(10)In collaboration with Regeneron.

(11)Trial ongoing in China only.

(12)Partnered with University of Pennsylvania.

(13)Partnered with Pfizer.

(14)Partnered with Fosun Pharma.

(15)Funded by the Gates Foundation.

(16)Funded by the Coalition for Epidemic Preparedness Innovations (CEPI).

A. Oncology Programs

1. Pumitamig (BNT327/BMS986545), a Bispecific Immunomodulator Candidate Targeting PD-L1 and

VEGF-A

Pumitamig is a bispecific immunomodulator candidate targeting both PD-L1 and VEGF-A. Pumitamig is currently

being evaluated in multiple Phase 2 and Phase 3 global and China-only clinical trials to assess its efficacy and

safety as monotherapy or in combination with chemotherapy, ADCs or mRNA-based cancer immunotherapies in

various indications. We and our partner, BMS, expect to have eight global registrational trials for pumitamig

ongoing by the end of 2026. Pumitamig is also being evaluated in combination with next-generation ADC

candidates trastuzumab pamirtecan (BNT323/DB-1303), BNT324/DB-1311, BNT325/DB-1305, BNT326/YL202

and BNT3212, and in combination with bispecific antibody candidates BNT314/GEN1059 and BNT3213.

ROSETTA Lung-01 Phase 3 Clinical Trial in First-Line Extensive-Stage Small Cell Lung Cancer, or ES-SCLC

A global Phase 3 clinical trial (NCT06712355) is being conducted to evaluate pumitamig in combination with

chemotherapy compared to atezolizumab in combination with chemotherapy as a first-line treatment for patients

with ES-SCLC.

–In June 2025, pumitamig received Orphan Drug Designation from the FDA for the treatment of small cell lung

cancer.

Phase 3 Clinical Trial in Second-Line Small-Cell Lung Cancer, or SCLC

A Phase 3 clinical trial (NCT06616532) is being conducted in China to evaluate pumitamig in combination with

chemotherapy compared to investigator’s choice chemotherapy as a second-line treatment for patients with

SCLC.

Phase 2 Clinical Trial in ES-SCLC

A global Phase 2 clinical trial (NCT06449209) is being conducted to evaluate pumitamig in combination with

chemotherapy in patients with untreated ES-SCLC and in patients with SCLC that progressed after first- or

second-line treatment. The trial is fully enrolled and treatment is ongoing.

–In September 2025, interim data from this trial were presented at the IASLC 2025 WCLC. The data, which are

consistent with data presented at European Lung Cancer Congress, or ELCC, 2025 from a Phase 2 clinical

trial conducted in China (NCT05844150), showed encouraging anti-tumor responses and a positive trend in

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progression free survival. Pumitamig plus chemotherapy was observed to have a manageable safety profile

with no new safety signals and a low discontinuation rate.

Phase 2 Clinical Trial in First-Line ES-SCLC

A Phase 2 clinical trial (NCT05844150) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a first-line treatment for patients with ES-SCLC.

–In March 2025, data from this trial were presented at the ELCC 2025 in Paris, France. Preliminary data

showed anti-tumor activity and an acceptable safety profile with no new safety signals beyond those typically

described for chemotherapy agents and anti-PD-(L)1 and anti-VEGF monotherapies. These data were the first

presented for pumitamig as a potential first-line treatment in ES-SCLC supporting the ongoing global

randomized Phase 3 clinical trial ROSETTA Lung-01 (NCT06712355).

–Updated data from this trial are expected to be presented at the ELCC 2026 taking place on March 25-28,

2026 in Copenhagen, Denmark.

Phase 2 Clinical Trial in Second-Line SCLC

A Phase 2 clinical trial (NCT05879068) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a second-line treatment for patients with SCLC.

–In March 2025, data from this trial were presented at the ELCC 2025. Preliminary data showed anti-tumor

activity, which was observed regardless of prior immuno-oncology treatment, and an acceptable safety profile.

ROSETTA Lung-201 Phase 3 Clinical Trial in Unresectable Stage III NSCLC

A global Phase 3 clinical trial (NCT07361497) to evaluate pumitamig compared to durvalumab following

concurrent chemoradiation therapy in patients with unresectable stage III NSCLC is planned to start in 2026.

ROSETTA Lung-202 Phase 3 Clinical Trial in First-Line NSCLC

A global Phase 3 clinical trial (NCT07361510) to evaluate pumitamig compared to pembrolizumab as a first-line

treatment for patients with advanced PD-L1 ≥ 50% NSCLC is planned to start in 2026.

ROSETTA Lung-02 Phase 2/3 Clinical Trial in First-Line NSCLC

A global Phase 2/3 clinical trial (NCT06712316) is being conducted to evaluate pumitamig in combination with

chemotherapy compared to pembrolizumab and chemotherapy as a first-line treatment for patients with NSCLC.

The Phase 2 portion of the trial is fully enrolled, and the Phase 3 portion is underway.

–We expect data from the Phase 2 part of this trial in 2026.

ROSETTA Lung-107 Phase 2 Clinical Trial in Second-Line NSCLC

A global Phase 2 clinical trial (NCT06841055) is being conducted to evaluate pumitamig in combination with

docetaxel as a second-line treatment for patients with NSCLC.

Phase 2 Clinical Trial in EGFR-mutant Non-Squamous NSCLC

A Phase 2 clinical trial (NCT05756972) is being conducted in China to evaluate pumitamig in combination with

chemotherapy in patients with EGFR-mutant non-squamous NSCLC who progressed after EGFR-tyrosine

kinase inhibitor treatment.

–Updated data from this trial are expected to be presented at the ELCC 2026 taking place on March 25-28,

2026 in Copenhagen, Denmark.

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ROSETTA Breast-01 Phase 3 Clinical Trial in Locally Advanced or Metastatic First-Line TNBC

A global Phase 3 clinical trial (NCT07173751) is being conducted to evaluate pumitamig in combination with

chemotherapy compared to chemotherapy alone as a first-line treatment for patients with PD-L1 combined

positive score, or CPS, ≤ 10 TNBC.

Phase 3 Clinical Trial in Locally Advanced or Metastatic First-Line TNBC

A Phase 3 clinical trial (NCT06419621) is being conducted in China to evaluate pumitamig in combination with

chemotherapy compared to chemotherapy alone as a first-line treatment for patients with locally advanced or

metastatic TNBC.

–Based on current event accrual projections, we expect first interim data from this trial in 2026.

Phase 2 Clinical Trial in Locally Advanced or Metastatic TNBC

A global Phase 2 clinical trial (NCT06449222) is being conducted to evaluate pumitamig in combination with

chemotherapy as a first- and second-line treatment for patients with locally advanced or metastatic TNBC.

–In December 2025, the first data from this trial were presented at the 2025 San Antonio Breast Cancer

Symposium, or SABCS. The data showed encouraging anti-tumor responses and a manageable safety profile

for pumitamig plus chemotherapy in first- and second-line treatment setting.

Phase 1/2 Clinical Trial in Locally Advanced/Metastatic TNBC

A Phase 1/2 clinical trial (NCT05918133) is being conducted in China to evaluate pumitamig in combination with

chemotherapy in patients with locally advanced or metastatic TNBC without previous systematic treatment.

ROSETTA CRC-203 Phase 2/3 Clinical Trial in Metastatic First-Line CRC

A global Phase 2/3 clinical trial (NCT07221357) is being conducted to evaluate pumitamig as a first-line

treatment for patients with microsatellite stable, or MSS, or Microsatellite Instability-Low and Proficient Mismatch

Repair, or MSI-L/pMMR, metastatic colorectal cancer.

Phase 2 Clinical Trial in Metastatic First-Line CRC

A Phase 2 clinical trial (NCT07133750) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a first-line treatment in patients with MSS or MSI-L/pMMR metastatic colorectal cancer.

–We expect data from this trial in 2026.

ROSETTA Gastric-204 Phase 2/3 Clinical Trial in Metastatic First-Line Gastric Cancer

A global Phase 2/3 clinical trial (NCT07221149) is being conducted to evaluate pumitamig in combination with

chemotherapy compared to nivolumab in combination with chemotherapy as a first-line treatment for patients

with metastatic gastric cancer.

ROSETTA HNSCC-205 Pivotal Clinical Trial in First-Line HNSCC

A global pivotal clinical trial evaluating pumitamig as a first-line treatment for patients with HNSCC is planned to

start in 2026.

Phase 2 Clinical Trial in First-Line Hepatocellular Carcinoma, or HCC

A Phase 2 clinical trial (NCT05864105) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a first-line treatment for patients with unresectable HCC.

–We expect data from this trial in 2026.

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ROSETTA HCC-206 Phase 1/2 Clinical Trial in First-Line HCC

A Phase 1/2 clinical trial (NCT07291076) is being conducted to evaluate pumitamig alone or in combination with

ipilimumab as a first-line treatment for patients with advanced or unresectable HCC.

Phase 2 Clinical Trial in First-Line Malignant Mesothelioma

A Phase 2 clinical trial (NCT05918107) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a first-line treatment for patients with malignant mesothelioma.

–In June 2025, the first data from this trial were presented at the 2025 ASCO Annual Meeting. The preliminary

data indicated anti-tumor activity and a manageable safety profile.

Phase 2 Clinical Trial in Second-Line Neuroendocrine Neoplasm, or NEN

A Phase 2 clinical trial (NCT05879055) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a second-line treatment for patients with NEN.

Phase 2 Clinical Trial in First-Line PDAC

A Phase 2 clinical trial (NCT07255404) is being conducted in China to evaluate pumitamig in combination with

chemotherapy as a first-line treatment for patients with metastatic PDAC.

Phase 2 Clinical Trial in Second-Line Glioblastoma

A Phase 2 clinical trial (NCT07297212) is being conducted in China to evaluate pumitamig alone or in

combination with temozolomide as a second-line treatment for patients with recurrent glioblastoma.

ROSETTA RCC-208 Phase 1/2 Clinical Trial in RCC

A Phase 1/2 clinical trial (NCT07293351) to evaluate pumitamig alone or in combination with ipilimumab or

cabozantinib in patients with advanced RCC is planned to start in 2026.

Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT05918445) is being conducted in China to evaluate pumitamig as a monotherapy

in patients with advanced solid tumors.

–Updated data from this trial are expected to be presented at the ELCC 2026 taking place on March 25-28,

2026 in Copenhagen, Denmark.

We have initiated several signal-seeking clinical trials to evaluate pumitamig with some of our proprietary novel

assets in our portfolio:

Combination with Trastuzumab Pamirtecan (BNT323/DB-1303) Phase 1/2 Clinical Trial in Advanced/Metastatic

Breast Cancer

A Phase 1/2 clinical trial (NCT06827236) is being conducted to evaluate trastuzumab pamirtecan in combination

with pumitamig in patients with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), human

epidermal growth factor (HER)2-low, ultra-low, or null advanced metastatic breast cancer or TNBC.

–We expect data from this trial in 2026.

Combination with BNT324/DB-1311 Phase 1/2 Clinical Trial in Advanced Lung Cancers

A Phase 1/2 clinical trial (NCT06892548) is being conducted to evaluate BNT324/DB-1311 in combination with

pumitamig in patients with advanced lung cancers.

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–We expect data from this trial in 2026.

Combination with BNT324/DB-1311 Phase 2 Clinical Trial in Advanced/Metastatic Solid Tumors

A Phase 2 clinical trial (NCT06953089) is being conducted to evaluate BNT324/DB-1311 in combination with

pumitamig or with TROP2 ADC candidate BNT325/DB-1305 in patients with advanced solid tumors.

–We expect data from this trial in 2026.

Combination with BNT325/DB-1305 Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT05438329) is being conducted to evaluate BNT325/DB-1305 in patients with

advanced solid tumors. As part of this clinical trial, pumitamig is being evaluated in combination with BNT325/

DB-1305 in various solid tumor indications.

–In April 2025, at AACR 2025 Annual Meeting, we presented the first clinical data evaluating the combination of

pumitamig plus BNT325/DB-1305. The interim data showed a manageable safety profile and early signs of

anti-tumor activity in a cohort with patients with platinum-resistant ovarian cancer, or PROC. Across the 13

efficacy evaluable patients with PROC, seven patients achieved partial response and three stable disease.

Responses were also observed in patients with NSCLC or TNBC.

–We expect data from the Phase 2 part of this trial in patients with TNBC in 2026.

Combination with BNT326/YL202 Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT07070232) is being conducted to evaluate BNT326/YL202 as monotherapy and in

combination with pumitamig in advanced solid tumors.

Combination with BNT326/YL202 Phase 1/2 Clinical Trial in Advanced NSCLC

A Phase 1/2 clinical trial (NCT07111520) is being conducted to evaluate BNT326/YL202 in combination with

pumitamig in advanced NSCLC.

–We expect data from this trial in patients with NSCLC or 2L+ EGFRm NSCLC in 2026.

Combination with BNT314/GEN1059 Phase 1/2 Clinical Trial in Advanced/Metastatic colorectal cancer

A Phase 1/2 clinical trial (NCT07079631) is being conducted to evaluate BNT314/GEN1059 in combination with

pumitamig and chemotherapy in patients with advanced colorectal cancer.

Combination with BNT3212 Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT07147348) is being conducted to evaluate BNT3212, a novel bispecific antibody-

drug conjugate candidate targeting EGFR and HER3, for use as monotherapy and in combination with

pumitamig in patients with advanced solid tumors.

Combination with BNT3213 Phase 1/2 Clinical Trial in First-Line HCC

A Phase 1/2 clinical trial (NCT06584071) is being conducted in China to evaluate pumitamig in combination with

BNT3213, a novel bispecific antibody candidate targeting TIGIT and PVRIG, as a first-line treatment for patients

with locally advanced or metastatic HCC.

2. iNeST and FixVac

a) Autogene Cevumeran (RO7198457/BNT122), an Individualized Neoantigen Specific Immunotherapy, or

iNeST

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Autogene cevumeran is an investigational individualized mRNA cancer immunotherapy based on specific

neoantigens that are present on a patient’s tumor.

BNT122-01 Phase 2 Clinical Trial in Adjuvant Colorectal Cancer, or CRC

A randomized Phase 2 clinical trial (NCT04486378) is being conducted to evaluate autogene cevumeran as an

adjuvant treatment of circulating tumor DNA, or ctDNA, positive, surgically resected Stage II (high risk)/Stage III

CRC. The trial is expected to enroll about 327 patients to evaluate the efficacy of autogene cevumeran

compared to watchful waiting after surgery and chemotherapy, which is the current standard of care for these

high-risk patients. The primary endpoint for the trial is disease-free survival, or DFS. Secondary objectives

include OS and safety.

–At the first pre-specified interim analysis of the ongoing BNT122-01 Phase 2 clinical trial, the futility boundary

was crossed. The interim analysis was reviewed by an independent Data and Safety Monitoring Board, or

DSMB, which is responsible for overseeing the safety and integrity of the trial. The DSMB considered

autogene cevumeran to be generally well tolerated with no new safety signals identified, and also indicated

that the data was not yet mature enough to draw reliable conclusions about efficacy, with a median follow-up

time for participants at the time of the analysis of approximately nine months, which was deemed to be

insufficient to evaluate the trial’s primary endpoint. This assessment is consistent with recent data from a

study published in Nature (Nakamura Y, et al., 2024), which showed that a majority of patients with ctDNA-

positive colorectal cancer experience disease recurrence within 24 months after surgery. However, because

the futility boundary was crossed, the DSMB was bound by its charter to make a non-binding recommendation

to terminate the study. Based on this assessment that the data are not yet mature enough to draw reliable

conclusions about efficacy, we have continued the trial in accordance with the protocol. The sponsor remains

masked, and interim data will not be disclosed at this time ensuring the integrity of the ongoing trial and

allowing for a comprehensive and mature assessment of the treatment’s efficacy at the final analysis of the

trial. The DSMB had no objections with the continuation of the study in the absence of safety concerns.

–An update from the ongoing Phase 2 trial in Stage II (high-risk)/ Stage III ctDNA+ adjuvant CRC is expected in

early 2026. Timing of the data read-out from the final analysis of this trial has been updated from 2026 to

2027, given that events have accrued more slowly than projected.

IMCODE004 Phase 2 Clinical Trial in Adjuvant High-risk Muscle-invasive Urothelial Carcinoma, or MIUC

A Phase 2 clinical trial (NCT06534983) is being conducted to evaluate autogene cevumeran as an adjuvant

treatment in combination with nivolumab compared to nivolumab alone in patients with high-risk MIUC. The trial

aims to enroll approximately 362 patients. The primary endpoint for the trial is investigator-assessed DFS.

Secondary endpoints include OS and safety.

We and our partner Roche have decided to discontinue the Phase 2 clinical trial (IMcode004; NCT06534983)

evaluating autogene cevumeran as an adjuvant treatment in combination with nivolumab compared to nivolumab

alone in patients with high-risk MIUC due to the rapidly emerging treatment landscape and shifting standard of

care.

IMCODE003 Phase 2 Clinical Trial in Adjuvant Pancreatic Ductal Adenocarcinoma, or PDAC

A Phase 2 clinical trial (NCT05968326) is being conducted to evaluate autogene cevumeran in combination with

atezolizumab followed by chemotherapy compared to chemotherapy alone as an adjuvant treatment for patients

with resected PDAC who have not received prior systemic anti-cancer treatment and showed no evidence of

disease after surgery. The trial aims to enroll 260 patients. The primary endpoint is DFS. Secondary endpoints

include OS and safety.

IMCODE001 Phase 2 Clinical Trial in First-line Advanced Melanoma

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The IMCODE001 (NCT03815058) trial was the first randomized Phase 2 clinical trial with autogene cevumeran

as part of the broader IMCODE study program. The trial evaluated the efficacy and safety of autogene

cevumeran in combination with pembrolizumab versus pembrolizumab alone as a potential first-line treatment for

patients with previously untreated advanced melanoma. The primary endpoint was progression free survival, or

PFS, and was events-based. Secondary endpoints included OS, ORR, DOR and safety. In January 2025, the

IMCODE001 trial was completed.

–In March 2025, topline results of the primary analysis were disclosed. While the initial data of the primary

analysis support the findings across the broader autogene cevumeran study program demonstrating that

autogene cevumeran can induce and expand high-magnitude and long-lived immune responses against the

encoded neoantigens in this aggressive stage of melanoma, the trial did not meet its primary efficacy endpoint

of statistically significant improvement of PFS in this advanced treatment setting. A numerical trend favoring

the combination arm in OS was observed. The combination of autogene cevumeran with PD-L1 checkpoint

blockade was well tolerated and adverse events were consistent with the known safety profiles of the

individual trial treatments, with no new safety signals observed.

–In October 2025, data from this trial including exploratory endpoints and biomarker correlations were

presented at the 2025 European Society For Medical Oncology, or ESMO, Congress. These data showed that

autogene cevumeran can induce durable immune responses against the encoded neoantigens that persisted

for up to 1.5 years after the last dose of autogene cevumeran. In the combination arm, the breadth of immune

response correlated with a prolonged PFS. Further translational data showed a trend of improved OS in the

combination arm compared to pembrolizumab monotherapy in patients with low tumor mutational burden, a

population that usually responds poorly to checkpoint inhibitor treatment, and in tumors where immune-cell

PD-L1 was high. These data support our therapeutic strategy to pursue autogene cevumeran to address the

unmet medical need in the adjuvant or minimal residual disease treatment settings. These settings are

characterized by lower tumor burden and heterogeneity, which aligns with the focus of our ongoing

randomized Phase 2 trials in colorectal and pancreatic cancer.

b) FixVac

FixVac is our fully owned, systemic, off-the-shelf mRNA-based cancer immunotherapy approach. FixVac

candidates are designed to target shared antigens that have been identified to be frequently expressed across

patients with a specific cancer type.

i. BNT111

BNT111 is designed to elicit an immune response to four antigens (NY-ESO-1, MAGE-A3, tyrosinase, TPTE) that

have each been found to be associated with cutaneous melanoma.

Phase 2 Clinical Trial in Anti-PD-(L)1 Refractory/Relapsed Unresectable Stage III or Stage IV Melanoma

A Phase 2 clinical trial (BNT111-01; NCT04526899) in collaboration with Regeneron Pharmaceuticals Inc., or

Regeneron, to evaluate BNT111 in combination with cemiplimab in patients with anti-PD-(L)1 refractory/relapsed,

unresectable Stage III or IV melanoma has been completed.

–In October 2025, data from this trial were presented at the 2025 ESMO Congress. As previously disclosed in

August 2024, the trial met its primary efficacy outcome measure, demonstrating a statistically significant

improvement in ORR in patients treated with BNT111 in combination with cemiplimab, as compared to a

historical control. The data showed that the combination of BNT111 and cemiplimab induced anti-tumor

responses that were deep and durable and a manageable safety profile for BNT111 as a single agent and in

combination. Follow-up data showed a positive trend towards improved long-term survival for the combination

of BNT111 and cemiplimab. No further development of BNT111 in advanced melanoma is currently planned.

ii. BNT113

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BNT113 contains two different RNAs encoding the two HPV16 oncoproteins E6 and E7, which are exclusively

expressed in pre-malignant and malignant tissue.

AHEAD-MERIT Phase 2/3 Clinical Trial in Unresectable Recurrent or Metastatic, PD-L1+, HPV16+ Head and

Neck Squamous Cell Carcinoma, or HNSCC

A Phase 2/3 clinical trial (AHEAD-MERIT; NCT04534205) is being conducted to evaluate BNT113 in combination

with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment for patients with unresectable

recurrent or metastatic, PD-L1+, HPV16+ HNSCC.

–In December 2025, the FDA granted Fast Track designation to BNT113 for the treatment of patients with PD-

L1+, HPV16+ HNSCC.

–Based on current event accrual projections, we expect data from the first interim analysis from the Phase 3

part of this trial in 2026.

iii. BNT116

BNT116 is comprised of six different NSCLC-associated tumor-associated antigens. BNT116 is being evaluated

in two clinical trials as monotherapy and in combination with other immunotherapies, ADCs and chemotherapies

in patients with advanced or metastasized NSCLC.

EMPOWERVAX Lung 1 Phase 2 Clinical Trial in PD-L1 ≥ 50% Advanced NSCLC

A Phase 2 clinical trial (NCT05557591) is being conducted in collaboration with Regeneron to evaluate BNT116

in combination with cemiplimab versus cemiplimab alone as a first-line treatment for patients with advanced

NSCLC whose tumors express PD-L1 in ≥ 50% of their tumor cells. The primary objective of the Phase 2 trial is

to assess the ORR per blinded-independent review committee.

LuCa-MERIT-1 Phase 1 Clinical Trial in NSCLC

A Phase 1 clinical trial (NCT05142189) is being conducted to evaluate the safety, tolerability and preliminary

efficacy of BNT116 as monotherapy and in several combinations including with chemotherapy, cemiplimab, and

some of our proprietary assets across various treatment lines and clinical settings in patients with NSCLC.

– In April 2025, at the 2025 Annual Meeting of the American Association for Cancer Research, or AACR, data

from a cohort with frail patients from the Phase 1 trial were presented. The preliminary data showed anti-tumor

activity, consistent immune response induction and a manageable safety profile in patients with PD-L1 positive

(TPS≥1%) unresectable Stage III or metastatic Stage IV NSCLC who are not eligible for chemotherapy as

first-line treatment.

–In September 2025, data were presented at the IASLC 2025 World Congress on Lung Cancer, or WCLC, from

a cohort evaluating BNT116 in combination with cemiplimab as consolidation treatment in patients with

NSCLC after receiving concurrent chemoradiotherapy. BNT116 in combination with cemiplimab demonstrated

encouraging event-free and overall survival rates and a manageable safety profile.

3. Antibody-Drug Conjugates

i. Trastuzumab Pamirtecan (BNT323/DB-1303), an ADC in Development in Collaboration with DualityBio

Trastuzumab pamirtecan is a topoisomerase-1 inhibitor-based ADC directed against Human Epidermal Growth

Factor Receptor 2, or HER2, a target that is over-expressed in a variety of cancers and contributes to the

aggressive growth and spread of cancer cells. The program received Fast Track Designation and Breakthrough

Therapy designation from the FDA for advanced endometrial cancer.

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DYNASTY-Breast02 Phase 3 Clinical Trial in Advanced or Metastatic HR+, HER2-low Breast Cancer

A Phase 3 clinical trial (NCT06018337) is being conducted to evaluate trastuzumab pamirtecan compared to

investigator’s choice of chemotherapy in advanced or metastatic HR+, HER2-low breast cancer subjects whose

disease has progressed on at least two lines of prior endocrine therapy or within six months of first-line

endocrine therapy and cyclin-dependent 4/6, or CDK4/6, inhibitor and no prior chemotherapy. The trial aims to

enroll approximately 532 patients. The primary endpoint is PFS. Secondary endpoints include OS, ORR, DOR

and safety, as well as patient-reported outcomes.

–Based on current event accrual projections, we expect interim data from this trial in 2026.

Phase 1/2 Clinical Trial in Advanced/Unresectable, Recurrent, or Metastatic HER2-Expressing Solid Tumors

A Phase 1/2 clinical trial (NCT05150691) is being conducted to evaluate trastuzumab pamirtecan in patients with

advanced/unresectable, recurrent, or metastatic HER2-expressing solid tumors.

–A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+) patients with advanced/recurrent

endometrial cancer has completed enrollment.

–We expect data from this cohort in 2026.

–We and DualityBio are continuing discussions with the FDA and plan to file a biologics license application, or

BLA, in second line endometrial cancer in 2026, subject to regulatory feedback.

Phase 3 Clinical Trial in Advanced Endometrial Cancer

A Phase 3 trial (NCT06340568) is being conducted to evaluate trastuzumab pamirtecan compared to

investigator’s choice of chemotherapy in patients with advanced and recurrent endometrial cancer. The trial aims

to enroll approximately 480 patients. The primary endpoints are PFS and ORR. Secondary endpoints include

OS, DOR and safety.

ii. BNT324/DB-1311, an ADC in Development in Collaboration with DualityBio

BNT324/DB-1311 is a topoisomerase-1 inhibitor-based ADC directed against B7H3. It has received Fast Track

Designation from the FDA for the treatment of patients with advanced/unresectable, or metastatic CRPC, who

have progressed on or after standard systemic regimens. It has also received Orphan Drug Designation from the

FDA for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma and SCLC.

Phase 3 Clinical Trial in Metastatic CRPC

A Phase 3 clinical trial (NCT07365995) to evaluate BNT324/DB-1311 compared to docetaxel in patients with

metastatic CRPC, is planned to start in 2026.

Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT05914116) is being conducted to evaluate BNT324/DB-1311 in patients with

advanced solid tumors.

–In June 2025 at the 2025 ASCO Annual Meeting, data from this trial were presented. In 73 patients with

heavily pretreated metastatic CRPC, BNT324/DB-1311 was observed to have a manageable safety profile

and showed encouraging preliminary clinical activity.

–In December 2025 at the 2025 ESMO Asia Congress, data from this trial were presented. In patients with

previously treated cervical cancer or platinum resistant ovarian cancer BNT324/DB-1311 showed encouraging

efficacy and a manageable safety profile.

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–In February 2026, updated data from this trial were presented at the ASCO GU Cancers Symposium.

BNT324/DB-1311 showed durable efficacy in heavily pretreated mCRPC patients with no new safety signals

reported.

iii. BNT325/DB-1305, an ADC in Development in Collaboration with DualityBio

BNT325/DB-1305 is a topoisomerase-1 inhibitor-based ADC directed against TROP2.

Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT05438329) is being conducted to evaluate BNT325/DB-1305 in patients with

advanced solid tumors. As part of this clinical trial, BNT325/DB-1305 is being studied in combination with

pumitamig in various solid tumor indications.

–In October 2025 at the 2025 ESMO Congress, data from this trial in patients with pretreated TNBC were

presented. Data showed BNT325/DB-1305 to have encouraging durable antitumor activity and a manageable

safety profile.

iv. BNT326/YL202, an ADC in Development in Collaboration with MediLink Therapeutics

BNT326/YL202 is a topoisomerase-1 inhibitor-based ADC directed against HER3.

Phase 1 Clinical Trial in Advanced or Metastatic EGFR-Mutated NSCLC or HR-Positive and HER2-Negative

Breast Cancer

A Phase 1 clinical trial (NCT05653752) is being conducted to evaluate BNT326/YL202 as a later-line treatment

in patients with locally advanced or metastatic EGFR-mutated NSCLC or HR-positive and HER2-negative breast

cancer.

Phase 2 Clinical Trial in Advanced Solid Tumors

A Phase 2 clinical trial (NCT06107686) is being conducted in China to evaluate BNT326/YL202 in patients with

advanced solid tumors.

–Data from this trial are expected to be presented at the ELCC 2026 taking place on March 25-28, 2026 in

Copenhagen, Denmark.

Phase 2 Clinical Trial in Multiple Breast Cancers

A Phase 2 clinical trial (NCT06439771) is being conducted in China to evaluate BNT326/YL202 in patients with

locally advanced or metastatic breast cancer with TNBC, HR-positive, HER2-zero-expression or HER2-low-

expression.

–In December 2025, data from this trial in patients with HR+ breast cancer with HER2-null (including HER2-

ultralow) or HER2-low expression were presented at the 2025 SABCS. Data showed BNT326/YL202 to have

encouraging antitumor activity and a manageable safety profile.

v. BNT329, an ADC for the Treatment of Advanced Solid Tumors

BNT329 is a fully owned carbohydrate antigen 19-9, or CA19-9, targeting ADC. CA19-9 is expressed in

pancreatic cancers and other solid tumors, plays a role in tumor adhesion and metastasis formation, and is a

marker of an aggressive cancer phenotype.

Phase 1/2 Clinical Trial in Advanced Solid Tumors

A Phase 1/2 clinical trial (NCT07186842) is being conducted to evaluate BNT329 in patients with advanced solid

tumors.

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4. Other Antibody Product Candidates

i. Gotistobart (BNT316/ONC-392), a Selective Treg Modulator Antibody Candidate in Development in

Collaboration with OncoC4

Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective regulatory T cell-depleting antibody

targeting cytotoxic T-lymphocyte associated protein 4, or CTLA-4, candidate being developed in collaboration

with OncoC4. The program received Fast Track Designation from the FDA in 2022, and Orphan Drug

Designation for the treatment of sqNSCLC in January 2026.

PRESERVE-003 Phase 3 Clinical Trial in NSCLC

A two-stage global Phase 3 trial (NCT05671510) is being conducted to evaluate the efficacy and safety of

gotistobart as monotherapy in patients with metastatic NSCLC that progressed under previous platinum-based

chemotherapy and PD-(L)1-inhibitor treatment.

–In December 2025, at the IASLC ASCO 2025 North America Conference on Lung Cancer, data from the non-

pivotal dose-confirmation stage of the two-stage global Phase 3 trial were presented. Gotistobart

demonstrated a clinically meaningful OS benefit compared to standard of care chemotherapy and a

manageable safety profile in sqNSCLC patients whose disease had progressed following anti-PD-(L)1 therapy

and platinum-based chemotherapy.

–Based on current event accrual projections, we expect interim data from the pivotal stage of the two-stage

Phase 3 trial in 2026.

PRESERVE-004 Phase 2 Clinical Trial in PROC

A Phase 2 clinical trial (NCT05446298) is being conducted to evaluate gotistobart in combination with

pembrolizumab in patients with PROC. The clinical trial is designed to evaluate multiple doses of gotistobart in

combination with a fixed dose of pembrolizumab in participants with ovarian cancer who are resistant to

platinum-based chemotherapy. The primary endpoints are ORR and safety. Secondary endpoints include DOR,

DCR, PFS and OS.

PRESERVE-006 Phase 1/2 Clinical Trial in Metastatic CRPC

A Phase 1/2 clinical trial (NCT05682443) is being conducted to evaluate the safety and efficacy of gotistobart in

combination with lutetium Lu-177 vipivotide tetraxetan in patients with mCRPC who have disease progressed on

androgen receptor pathway inhibition. The primary endpoints are PSA50 and safety.

–In June 2025, data from the Phase 1 part of this trial were presented at the ASCO Annual Meeting and in

February 2026, updated data from the Phase 1 part were presented at the ASCO GU Cancers Symposium..

The data indicated a manageable safety profile and preliminary clinical activity for gotistobart in combination

with Lu 177 in patients with mCRPC.

–We expect data from the Phase 2 part of this trial in 2026.

PRESERVE-001 Phase 1/2 Clinical Trial in Advanced or Metastatic Solid Tumors

A Phase 1/2 dose escalation clinical trial (NCT04140526) is being conducted to evaluate gotistobart as a single

agent and in combination with pembrolizumab in patients with advanced or metastatic solid tumors.

–In June 2025, at the 2025 ASCO Annual Meeting, updated data from the melanoma cohorts of the ongoing

trial were presented. The data suggested encouraging preliminary clinical activity and a manageable

tolerability profile with no new safety signals observed.

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ii. BNT314/GEN1059 is being developed in collaboration with Genmab. BNT314/GEN1059 is a potential first-in-

class bispecific antibody product candidate designed to boost antitumor immune responses through epithelial

cell adhesion molecule-, or EpCAM-, dependent 4-1BB agonistic activity.

Phase 1 Clinical Trial in Advanced or Metastatic Solid Tumors

A Phase 1 clinical trial (NCT06150183) is being conducted to evaluate the safety and preliminary antitumor

activity of BNT314/GEN1059 in patients with advanced or metastatic solid tumors.

iii. BNT317, an Antibody for the Treatment of Advanced Solid Tumors

Phase 1 Clinical Trial in Advanced Solid Tumors

A Phase 1 clinical trial (NCT06750185) is being conducted to evaluate the safety, tolerability, pharmacokinetics,

and immunogenicity of BNT317 in participants with advanced solid tumors.

5. Oncology Cell Therapy Product Candidates

i. BNT211, a chimeric antigen receptor, or CAR, T-cell therapy – CAR-T - in multiple solid tumors

BNT211 is a novel approach combining an autologous tumor-specific CAR-T cell therapy candidate targeting the

oncofetal antigen Claudin-6 (CLDN6) with a CLDN6-encoding CAR-T cell amplifying RNA vaccine, or CARVac,

that is based on BioNTech’s FixVac platform in one regimen.

Phase 1 Clinical Trial in CLDN6-Positive Relapsed or Refractory Solid Tumors

A Phase 1 dose escalation clinical trial (NCT04503278) is being conducted to evaluate BNT211 as monotherapy

or in combination with CARVac in patients with CLDN6-positive relapsed or refractory solid tumors, including

non-small cell lung cancer, gastric cancer, ovarian cancer and testicular germ cell tumors.

B. Infectious Disease Programs

1. Next-Generation COVID-19 Vaccine

In collaboration with Pfizer, we are aiming to develop a vaccine candidate that enhances and broadens SARS-

CoV-2 immunogenicity responses.

2. COVID-19 – Influenza Combination mRNA Vaccine Program – BNT162 + BNT161

In collaboration with Pfizer Phase 1/2 clinical trials are being conducted to evaluate the safety, tolerability and

immunogenicity of the combination of the companies’ mRNA vaccine candidates against influenza and

COVID-19. We expect to provide updates as the program progresses.

3. Herpes Simplex Virus Vaccine Program – BNT163

A Phase 1 clinical trial (NCT05432583) is being conducted to evaluate the safety, tolerability, immunogenicity

and preliminary efficacy of BNT163 for the prevention of genital lesions caused by HSV-2 and potentially HSV-1.

–In October 2025, data from this trial were presented at the 2025 Infectious Disease Week, or IDWeek,

congress. The data showed BNT163 was well-tolerated with an acceptable safety profile and induced binding

antibody and neutralizing titers to HSV-2 antigens.

4. Tuberculosis Vaccine Program - BNT164

In December 2025, a Phase 1a clinical trial (NCT05537038) to evaluate the safety, reactogenicity, and

immunogenicity of BNT164 was completed.

A Phase 1b/2a clinical trial (NCT05547464) is being conducted to assess the safety, reactogenicity, and

immunogenicity of mRNA vaccine candidates against tuberculosis disease.

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5. Malaria Vaccine Program – BNT165

A Phase 1/2 trial (NCT06069544) to evaluate the safety, tolerability, immunogenicity and efficacy of a second

investigational RNA-based vaccine candidate is on clinical hold by the FDA, as announced on March 4, 2025.

BioNTech has complied with the hold by the FDA and, in accordance with the clinical trial protocol, had

proactively paused the study. BioNTech is assessing next steps in the development of this vaccine candidate.

6. Mpox Vaccine Program – BNT166

A Phase 1/2 clinical trial (NCT05988203) is being conducted to evaluate the safety, tolerability, reactogenicity

and immunogenicity of an mRNA-based multivalent vaccine candidate (BNT166a).

–In October 2025, data from the Phase 1 portion of this trial were presented at the 2025 IDWeek congress. The

data showed that BNT166 was well-tolerated and induced multiantigen-directed antibodies with cross-mpox

virus clade and cross-orthopoxvirus neutralization activity in vaccinia virus-naïve and experienced participants.

A randomized, placebo-controlled Phase 2 clinical trial (NCT07379580) is being conducted to evaluate the

safety, reactogenicity, and immunogenicity of BNT166 in healthy participants.

7. Shingles Vaccine Program – BNT167

A Phase 1/2 clinical trial (NCT05703607) to evaluate the safety, tolerability, and immunogenicity of BNT167 in up

to 900 healthy volunteers 50 through 69 years of age was terminated.

–Both we and Pfizer have decided to opt-out of the further development of BNT167.

8. HIV Antibody Program – BNT351

In February 2026, the first patient was dosed in a Phase 1 clinical trial (NCT07392372) to evaluate the safety,

pharmacokinetics, and antiviral activity of BNT351 in adults living with and without HIV.

VI. Sales, Marketing and Distribution

Our commercial organization currently focuses on supporting sales of our COVID-19 vaccine in Germany and

Türkiye. Our commercial organization is responsible for promoting our products to health care providers and

providing information to stakeholders, including governmental organizations, in Germany and Türkiye.

As a result of our partnership with Pfizer, under which our commercialization responsibilities are limited to

Germany and Türkiye, we maintain a lean fixed cost base for our COVID-19 vaccine business.

Our commercial organization is also responsible for preparing and obtaining reimbursement from third-party

payors, including governmental organizations, for our COVID-19 vaccine.

We aim to build a specialized oncology sales force in major markets, including North America and Europe, while

leveraging our commercial partners for co-commercialization. We are working towards being commercial-ready

in anticipation of potential commercial oncology launches as soon as 2027, if approved.

VII. Manufacturing

We are building a fully integrated biotechnology company, with operations spanning from research through

clinical development, manufacturing and sales and marketing. To successfully bring individualized

immunotherapies and vaccines to people around the world, we believe that it is crucial to have in-house

manufacturing capabilities that can be efficiently scaled for global clinical and commercial distribution. We have

several manufacturing sites capable of developing automated production processes for on-demand production of

our investigational therapies and vaccines. These can be classified into distinct GMP manufacturing capabilities.

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We operate GMP-certified manufacturing facilities in Germany, where we manufacture mRNA therapeutics and

engineered cell therapies for both our own pipeline, including a state-of-the art, multi-platform, GMP-certified

manufacturing facility located in Marburg, Germany. We also operate a fifth facility in Germany where we

manufacture custom peptides both to support our extensive immunomonitoring activities within our development

programs and for third parties. Our subsidiary BioNTech Innovative Manufacturing Services GmbH, or BioNTech

IMFS, has been manufacturing GMP-certified cellular products since 1999.

Outside of Germany, we operate manufacturing sites in Zhuhai and Nantong, China. The Zhuhai site serves as a

local R&D and biotech hub, while the Nantong site serves as an industrial-scale antibody production (drug

substance and drug product) facility for clinical programs. We are building a BioNTainer site in Kigali, Rwanda,

with the intent to enable robust end-to-end manufacturing in Africa for mRNA-based medicines. Furthermore, we

are advancing the development and commissioning of a state-of-the-art mRNA manufacturing facility at La Trobe

University in Melbourne, Australia, and have established R&D mRNA manufacturing capabilities in leased

laboratory space at the university.

Our approach has been to proactively build capacity in anticipation of demand from both internal research and

development from our collaborators. We have done so by continuing to make significant investments in our

manufacturing infrastructure, including our capacity to manufacture mRNA, viral vectors, cellular products and

peptides. We believe that the development and optimization of our manufacturing processes in parallel to drug

development is crucial to our success.

A. Manufacturing Operations

COVID-19 Vaccine. Our manufacturing site in Marburg was approved by the EMA for manufacturing of our

COVID-19 drug product in March 2021. This approval made it one of the largest mRNA manufacturing sites

worldwide. In addition, we have another GMP facility that currently produces our COVID-19 vaccine candidates

for clinical trials. We have a network of sub-contractors established to provide drug products, and fill and finish

services to enable production.

mRNA. We believe scaling up manufacturing for mRNA can best be executed as part of a proprietary

manufacturing approach, rather than as part of an outsourcing strategy. We believe this approach allows us to

maintain control of our proprietary processes and gives us the flexibility we need for scheduling batch production

for our drug substances to match our development plans as they evolve. Our mRNA manufacturing is currently

conducted at our in-house BioNTech IMFS facility, our BioNTech East Wing facility, and our Marburg facility. The

East Wing facility manufactures iNeST (finished product). BioNTech IMFS produces DS, formulated Drug

Product as well as precursors (Liposomes) for early clinical supply. Our manufacturing facility in Marburg is one

of the largest mRNA vaccine manufacturing sites worldwide with an annual capacity of up to three billion doses

of mRNA drug substance and we believe we are well positioned to supply the quantities required by global

market demand.

Cell Therapy Products. We have end-to-end capabilities and teams in Germany with over 20 years of experience

in cell therapy manufacturing, quality control and release. Our cell therapy programs target novel and known

tumor-specific antigens, including patient-specific mutant neoantigens. We also leverage our mRNA vaccine

technology to further boost T-cell activation, expansion, and persistence. Our state-of-the-art manufacturing

processes of cellular products involve the isolation of primary human blood cells and subpopulations, such as,

e.g., CD3+ T cells. At our BioNTech IMFS facility, cell products are cultured, expanded and genetically modified

(e.g., CAR-T cells) in an aseptic automated production process in specialized cleanroom facilities with a turn-

around time of below 35 days. We also have the capability for in-house mRNA production for the genetic

modification of such innovative cell therapy products.

Peptides. Our custom peptide synthesis business has developed unique technologies to produce several million

peptides over the past ten years to support our growing clinical pipeline. These include fast small-scale

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manufacturing of peptides for target and epitope discovery as well as for neoepitope characterization and

production of high content arrays. It is important to synthesize highly purified peptides in order to avoid false

positives in immunomonitoring in our mRNA immunotherapy trials. We also use peptides as starting materials in

our engineered cell therapies as well as in some drug formulations and biomarker discovery studies. We have

developed proprietary technologies to produce highly complex and purified peptide pools that consist of

overlapping peptides spanning entire antigens or neoepitopes. In September 2025, we moved into a new

manufacturing plant in Berlin, which approximately doubled our manufacturing capacity to produce peptides and

diversified our peptide activities towards new fast-growing markets.

B. Manufacturing Facilities

The information included herein is as of the date of this Annual Report.

Manufacturing sites in Germany

Marburg

Marburg is one of our fully owned, state-of-the-art manufacturing facilities for just-in-time delivery and scalable

production. Our Marburg manufacturing facility comprises eight large and small molecule production suites. It is

one of the largest mRNA vaccine manufacturing sites globally. The facility has the capacity to produce up to

three billion doses of mRNA drug substance vaccine annually.

Marburg is our central hub for innovation and development of novel manufacturing solutions. It is a center of

excellence, not only in terms of facilities and devices, but as a know-how hub with appropriate and forward-

looking staff training. We have about 450 employees on site. To ensure production, we work in flexible/different

shift models up to 24/7 if required.

Idar-Oberstein

BioNTech IMFS: Our manufacturing operations for cell therapy products and clinical bulk mRNA are housed in

our wholly owned subsidiary. Founded in 1997, BioNTech IMFS specializes in services for innovative therapeutic

approaches. In 2009, BioNTech IMFS became our wholly owned subsidiary, giving us access to synergistic

platforms and complementary expertise for development, testing and manufacturing services. BioNTech IMFS

and its predecessors have had GMP-certified cell and gene therapy manufacturing capabilities since 1999, and

obtained GMP manufacturing authorization for mRNA production in 2011. In 2017, BioNTech IMFS began

automated manufacturing of the iNeST product candidate and entered its first commercial supply contract for

retroviral vectors. The BioNTech IMFS facility is located near Mainz. Around 500 staff members are employed at

this facility, with collective expertise in molecular biology, cell biology and virology and a close working

relationship with our R&D teams in Mainz. We consider BioNTech IMFS our powerhouse for early-stage mRNA

material.

Mainz

BioNTech iNeST Clinical Manufacturing (East Wing): We utilize our GMP-certified manufacturing facility at our

headquarters in Mainz, Germany for the production of iNeST immunotherapies. In 2015, our wholly owned

subsidiary, BioNTech RNA Pharmaceuticals GmbH, or BioNTech RNA, and Siemens announced a collaboration

for developing an automated, paperless and digitalized production site for individualized mRNA. We obtained our

GMP manufacturing authorization for iNeST production at our East Wing facility in June 2018 and manufactured

our first drug product there the following month.

Over 300 staff members are employed at this facility and operate it seven days per week. In its first year of

operation, the facility manufactured and released more than 250 batches of mRNA and has manufactured and

released more than 1,700 batches of mRNA since inception.

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To perform our target identification process to feed into the iNeST downstream GMP manufacturing process, our

headquarters also hold our core facility, which operates under Good Clinical Practice, or GCP, for labs. Incoming

patients’ materials (blood and tumor samples) are received and analyzed to identify characteristic mutations to

generate the patient-specific target list used for individualized mRNA production.

BioNTech Clinical Manufacturing: Our GMP-certified manufacturing facility in Kupferbergterrasse, Mainz is

authorized to conduct secondary packing, labeling, storage and batch release of primary packed investigational

medicinal products.

Another GMP facility in Mainz for mRNA-based products was completed in 2025, with a target manufacturing

license date of 2027. With advanced automation and streamlined processes, this new facility is designed to

serve a high four-digit number of patients annually.

Tübingen

In January 2026, we became the sole owner of the German mRNA company CureVac’s business operations.

CureVac’s Tübingen site is a GMP-compliant mRNA manufacturing hub primarily designed for clinical-stage

supply. It includes multiple multi-product GMP suites and an upscaled facility planned for supporting late-stage

trials and potentially commercial supply. A key asset is the automated “RNA Printer” enabling small-batch, end-

to-end mRNA and LNP production suited for personalized oncology.

Berlin

JPT, our peptide manufacturing facility located in Berlin, was established in 2004 and became a wholly owned

subsidiary of BioNTech in 2008. JPT has manufacturing capacity to produce up to 1 million peptides per year for

research applications, including drug discovery and bioanalysis.

Global manufacturing sites

Outside of Europe, we maintain sites in China, Rwanda and Australia.

Nantong and Zhuhai, China

Biotheus, now a BioNTech subsidiary, operates two strategic Chinese sites linked to its biologics pipeline. Its

Zhuhai location serves as a local R&D and biotech hub, with GMP production for early-phase clinical trials. The

larger Nantong campus provides industrial-scale antibody production (drug substance and drug product) for

clinical programs and is intended to support initial launches and ongoing commercial supply. Currently, Nantong

operates a single drug substance line with three 2000-liter reactors and one filling line. A second drug substance

line is under construction.

The BioNTainer: a platform for localized and sustainable mRNA production

The BioNTainer is an example of our innovative approach to establishing scalable vaccine production. It was

developed to ensure sustainable, equitable access to our programs, particularly in low-income countries and

regions with limited infrastructure. The BioNTainer allows scalable vaccine production by developing and

delivering mRNA manufacturing facilities based on a containerized clean room solution with a modular design,

standardized equipment, and software components. Each BioNTainer unit is a clean room, which we equip with

state-of-the-art manufacturing solutions for the manufacture and formulation of mRNA-based vaccines. Each

BioNTainer unit is built of six to eight ISO-sized containers. A BioNTainer unit can be equipped to manufacture a

range of mRNA-based vaccines targeted to regional needs: for example, our COVID-19 vaccine and our

investigational malaria, tuberculosis, or mpox vaccines, if they are successfully developed, approved, and

authorized by regulatory authorities and in line with regional demand. The BioNTainer units can also support

clinical-scale manufacturing of investigational mRNA-based medicines.

Kigali, Rwanda Manufacturing Facility

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Our first international BioNTainer site was the BioNTainer manufacturing facility in Kigali, Rwanda. The Kigali

facility was planned to install two sets of BioNTainer units for commercial-scale bulk production of mRNA

vaccines with the intent to enable robust end-to-end manufacturing in Africa for mRNA-based medicines. The

first BioNTainer unit arrived in Kigali, Rwanda in 2023. We acknowledged this important milestone in progressing

mRNA vaccine manufacturing capabilities in Africa with the inauguration of our site in Kigali, Rwanda.

In 2024, we announced that CEPI would be committing up to $145 million to support us to establish further

mRNA clinical-scale manufacturing capabilities at the Kigali facility. The setup of clinical-scale manufacturing

capabilities for mRNA-based vaccine candidates involves the installation of two additional BioNTainer units at

the Kigali facility - one unit for clinical scale Drug Substance and bulk Drug Product production and one unit for

vaccine filling. The clinical scale BioNTainer units are expected to be installed in 2026 and are intended to

produce and fill up to 500,000 doses of clinical trial material and/or commercial vaccines per year. We plan to

apply for a GMP manufacturing license in 2027. Under the terms of the agreement with CEPI, we intend to

provide sustainable supply of our prophylactic vaccines manufactured at the Kigali facility if successfully

developed and authorized, such as vaccines against malaria, mpox and tuberculosis, to low and lower middle-

income countries, with priority supply to African countries.

The facility’s manufacturing capacity will depend on the mRNA product being manufactured and various factors,

such as dosage and formulation. For commercial vaccine production or in response to a pandemic, we may

activate all installed BioNTainers on site and could potentially manufacture up to 50 million doses annually of a

product, using an RNA process similar to that used for the COVID-19 vaccines by Pfizer and us.

The European Investment Bank, or EIB, and European Commission, or EC, are supporting the development of

our mRNA manufacturing site in Rwanda. In October 2025, up to €95 million in blended EC and EIB financing

was awarded to support site infrastructure and facility operations and to develop contract development

manufacturing organization capabilities with the goal of enabling the manufacture of clinical trial materials for

local partners. Our partnership with CEPI and the EC/EIB strengthens Africa’s vaccine ecosystem.

By the end of 2025, BioNTech Rwanda employed approximately 40 people from eight different African countries

and is expected to continue to grow in 2026.

Melbourne, Australia Manufacturing Facility

In 2023, we signed a multi-year strategic partnership with the State of Victoria, Australia, for an initiative to

strengthen the local mRNA ecosystem with our BioNTainer technology. This partnership aims to provide high-

tech manufacturing capabilities and our expertise to develop projects for further research and development.

We are advancing the development and commissioning of our state-of-the-art mRNA manufacturing facility on

the Bundoora campus of La Trobe University in Melbourne. Having broken ground on the site in 2024,

construction activities on the building structure have gained momentum. In November 2025, we celebrated the

“topping-out” of the building, with the successful completion of the concrete superstructure. Once operationally

ready, the facility is intended to support Australia’s growing mRNA ecosystem by producing R&D and cGMP

clinical-scale investigational mRNA-based medicines.

In advance of the completion of our R&D and clinical-scale mRNA manufacturing facility, in mid-2025, we

established R&D mRNA manufacturing capabilities in leased laboratory space at La Trobe University. In October

2025, we celebrated the successful manufacture of mRNA on Australian soil. Our R&D mRNA manufacturing

services are now available to the growing mRNA ecosystem, and we expect our capabilities to expand through

2026. Upon completion of construction, we expect to transfer our R&D processes and equipment trains into our

own facility.

Following the opening of our Innovation Center in Melbourne’s central business district in mid-2024, our local

scientific and strategic leadership team made a concerted effort to engage with and integrate into the mRNA

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ecosystem in Australia and the broader region. We expect to continue to leverage our local and global expertise

to assess and identify mRNA-focused research projects from academia and industry and facilitate their transition

to clinical-stage development as potential future product candidates.

C. Other Certifications

BioNTech Diagnostics has a quality management system that is certified according to ISO 13485:2016 and JPT

maintains an ISO 9001:2015 certified Quality Management System.

D. Quality Assurance

We have implemented and maintain several Quality Assurance systems. BioNTech IMFS, BioNTech Clinical

Manufacturing and BioNTech iNeST Clinical Manufacturing have implemented GMP-certified quality assurance

systems. BioNTech Diagnostics has a quality management system that is certified according to ISO 13485:2016

and JPT maintains an ISO 9001:2015 certified Quality Management System.

VIII. Third-Party Collaborations

We have forged productive collaborations with pharmaceutical companies and academic research institutions

with area expertise and resources in an effort to advance and accelerate our discovery and development

programs in oncology, and also to leverage our drug classes into additional disease indications while minimizing

our incremental costs.

Our collaborations include, without limitation:

–Bristol Myers Squibb to jointly develop, manufacture and commercialize pumitamig;

–DualityBio for the research and development of certain antibody drug conjugates;

–Genentech for our iNeST platform in our mRNA drug class;

–Genmab for our next-generation checkpoint immunomodulator platform in our protein-based therapeutics drug

class;

–OncoC4 for the research and development of certain monoclonal anti-CTLA4 antibodies; and

–Pfizer for our COVID-19 vaccine program, which leverages technology from our infectious disease mRNA-

based platform.

We either wholly own or retain significant rights to all of our clinical stage programs, either in the form of a global

share of profit and co-commercialization rights with our collaborators in certain markets or significant royalties

and milestones. We plan to continue to identify potential collaborators who can contribute meaningful resources

and insights to our programs and allow us to more rapidly expand our impact to broader patient populations.

A. BMS Collaboration

On June 2, 2025, we entered into a Global Co-Development and Co-Commercialization Agreement, which we

refer to as the Original Agreement, with Bristol Myers Squibb Company, or BMS, to jointly develop, manufacture

and commercialize our investigational bispecific antibody pumitamig across numerous solid tumor types.

Other than the right to receive upfront payment, non-contingent anniversary payments and development and

regulatory approval milestones (which stay with BioNTech SE), we assigned our rights and obligations under the

Original Agreement to our subsidiary BioNTech US Inc. pursuant to an Assignment and Assumption Agreement

dated June 2, 2025 which was amended on August 15, 2025. In connection with the assignment, the parties also

entered into a Parent Guarantee in favor of BMS dated June 2, 2025. The Original Agreement was amended and

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restated on August 15, 2025 to further define the performance-related rights and obligations of the collaboration,

which, as so amended and restated, we refer to as the BMS Agreement.

Under the BMS Agreement, BMS paid us $1.5 billion in an upfront payment and agreed to pay $2 billion total in

non-contingent anniversary payments through 2028. Furthermore, we will be eligible to receive up to $7.6 billion

in additional development, regulatory and commercial milestones. The parties will equally share global profits

and losses.

The parties have agreed to use commercially reasonable efforts to jointly develop pumitamig, as a monotherapy

or in combination with other products, pursuant to a Joint Development Plan, or JDP. Development costs will

generally be shared equally; provided, if a particular joint clinical trial involves pumitamig in combination with a

proprietary or in-licensed asset of either party, cost sharing will be on an adjusted basis, subject to certain

exceptions.

Each party may propose new clinical trials for additional indications or combinations to be added to the JDP. If

the other party declines co-funding of a proposed new trial in the JDP, the proposing party may proceed

independently at its own cost, under the oversight of the Joint Development Committee, subject to certain

reimbursement rights against the other party.

The parties have also agreed to use commercially reasonable efforts to jointly commercialize pumitamig

pursuant to a jointly-developed global commercialization strategy and certain co-commercialization and market

access plans. The parties will equally share any profits and losses from the commercialization of pumitamig. A

Joint Commercialization Committee will coordinate and allocate commercial responsibilities, including the “lead”

role with respect to specific activities, in an equitable manner to maximize the success of pumitamig and to

maximize the efficiencies of the collaboration and avoid duplication of efforts as much as possible. Each party

has the right to contribute equally (on a market-by-market basis) to all strategic commercial planning and

execution, subject to certain exceptions.

We will be solely responsible and will use commercially reasonable efforts for the global clinical supply of

pumitamig initially before the completion of a manufacturing technology transfer from us to BMS. Following the

completion of the manufacturing transfer, we will continue to be responsible and will use commercially

reasonable efforts for the global clinical supply of pumitamig, but the parties may agree for BMS to manufacture

certain quantities of the clinical supply. Following the completion of the manufacturing transfer and BMS being

otherwise ready to manufacture and supply at scale, BMS will be responsible for the commercial supply of

pumitamig, provided that we retain the right to contribute a certain percentage of global commercial supply,

subject to certain conditions.

Each party has granted to the other party certain co-exclusive licenses under its intellectual property, or IP,

including patents and know-how (including to each party’s share of any future jointly owned IP under the BMS

Agreement), to perform development and medical affairs activities with respect to seek and obtain regulatory

approvals of, and manufacture, commercialize and otherwise exploit pumitamig.

The parties have also agreed to a mutual right of first negotiation, effective from the date of the BMS Agreement

through the fifth anniversary thereof, with respect to certain events related to next generation antibodies, where

either party (a) receives a transaction proposal from a third party, (b) intends to enter into such a transaction with

a third party, or (c) determines to initiate a registrational trial for such next generation antibody.

The term of the BMS Agreement commenced on June 2, 2025 and will remain in effect until and unless the

parties mutually agree to permanently terminate and cease all exploitation of pumitamig, or the BMS Agreement

is otherwise earlier terminated by the parties in accordance with its terms. BMS has the right to terminate for

convenience by giving a specified period of prior notice. BMS may also terminate if BMS determines in good

faith that there is unacceptable risk for harm in humans relating to pumitamig that is not resolved, or a Safety

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Issue. Each party may also terminate for uncured material breach or insolvency of the other party. In the event

that the termination is by BMS for convenience or by us for uncured material breach, the parties will continue to

co-fund certain ongoing clinical trials until the earlier of the completion or wind-down of such clinical trials or the

conclusion of a specified period from the date of notice of termination. Upon termination, all licenses granted

under the BMS Agreement will terminate, except that BMS will grant us a reversion license (other than where

termination is by BMS for a Safety Issue) to BMS’s interest in specified reversion IP to allow us to continue

developing and commercializing licensed products in the form such licensed products existed as of the date of

termination, subject to the parties agreeing on the financial payments for such reversion license. The grant of the

reversion license is contingent on (i) the parties’ agreement upon commercially reasonable financial payments

and (ii) the parties entering into a reasonable license agreement for the reversion license. In the event that the

parties cannot agree on commercially reasonable financial payments during a specified period, the parties will

refer such matter for resolution by baseball arbitration. During the period between termination and entry into the

reversion license (or a specified period following the termination date, if earlier), BMS may not bring any claim

against us for infringement of any reversion IP in the conduct of any development activities ongoing as of the

termination date.

B. DualityBio Global Strategic Partnership

In 2023, we entered into three License and Collaboration Agreements with DualityBio, which we refer to as the

DualityBio Agreements. Each of the DualityBio Agreements relates to specific ADC assets. The first agreement,

the HER2 Agreement, relates to the ADC asset targeting HER2 and was entered into on March 16, 2023. The

second agreement, the B7H3 Agreement, relates to the ADC asset targeting B7H3 and was entered into on

March 31, 2023. The third agreement, the TROP2 Agreement, relates to the ADC asset targeting TROP2 and

was entered into on August 4, 2023.

Each of the three DualityBio Agreements relates to a license granted to us with respect to certain patents and

know-how owned or otherwise controlled by DualityBio and our collaboration with DualityBio in the research and

development of ADC therapeutics.

In each of the DualityBio Agreements, DualityBio granted us the exclusive, royalty-bearing and sublicensable

right to exploit certain patents and know-how, which we refer to as the DualityBio IP, for the research,

development, manufacture and commercialization of the respective ADC compound and pharmaceutical

products comprising such compound, which we refer to as the DualityBio Products, in any field in the territory,

which is all countries of the world except for mainland China, Hong Kong and Macau, which we refer to as the

DualityBio Retained Territory. We were also granted the sole right to exploit the DualityBio IP to develop and

manufacture the DualityBio Products in the DualityBio Retained Territory solely for the purpose of developing,

manufacturing and commercializing the DualityBio Products in the territory.

Each party has final decision-making authority and is generally responsible for clinical trial supply costs and

regulatory activities and costs with respect to their respective territory.

We are responsible for the commercialization of any DualityBio Products in the territory.

The B7H3 Agreement also grants DualityBio the option to share the development and commercialization costs

and the profits and losses from the exploitation of the first original DualityBio Product in the United States. Under

the B7H3 Agreement, we have further granted to DualityBio the option to assume a percentage of the total sales

force of the first original DualityBio Product in the United States.

In partial consideration of DualityBio’s granting of the licenses and rights to us under the DualityBio Agreements,

we have made upfront payments to DualityBio in an aggregate amount of $220 million. In addition, we agreed to

make potential payments upon the achievement of specified development, regulatory and commercial

milestones. Such milestone payments could amount up to $2.6 billion in the aggregate (the TROP2 Agreement

also provides for additional sales milestone payments in the event DualityBio works on, and we exercise, the

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option regarding the next-generation product). We further agreed to between single-digit to double-digit tiered

royalties on net sales of all DualityBio Products, which also differ between the DualityBio Agreements. Royalties

are subject to stacking provisions and will be reduced in case of respective biosimilar products entering the

market. Furthermore, we agreed to reimburse DualityBio for certain development costs.

The DualityBio Agreements end on a country-by-country and DualityBio Product-by-DualityBio Product basis

upon expiration of the respective last DualityBio royalty term for a DualityBio Product in that country. Thereafter,

the licenses granted to us with respect to such product in such country will convert into a perpetual, exclusive,

fully paid-up and royalty-free license. In addition to termination rights granted to each party in the case of the

other party’s uncured material breach or insolvency, we may terminate each DualityBio Agreement, in whole or in

part, for convenience upon prior written notice.

On November 12, 2024, we and DualityBio entered into a side letter to the DualityBio Agreements to undertake

certain development activities in the territory and DualityBio Retained Territory with DualityBio Products in

combination with other product(s) that are proprietary to or owned or controlled by us or our affiliates.

C. Genentech iNeST Collaboration

Collaboration Agreement

On September 20, 2016, we entered into a Collaboration Agreement with Genentech and F. Hoffman-La Roche

Ltd, together with all amendments thereto, collectively referred to as the Genentech Collaboration Agreement, to

jointly research, develop, manufacture and commercialize certain pharmaceutical products that comprise

neoepitope RNAs, or the Genentech Collaboration Products, which include our iNeST development candidates,

for any use worldwide. Under the Genentech Collaboration Agreement, we and Genentech agreed to perform

joint research under a research plan to further improve our technology platform for the manufacturing of

Genentech Collaboration Products. Under the terms of the Genentech Collaboration Agreement, Genentech paid

us $310 million in upfront and near-term milestone payments.

We and Genentech must use commercially reasonable efforts to jointly develop one or more Genentech

Collaboration Products in accordance with an agreed global development plan, with the costs of such

development to be shared equally. We continued certain clinical studies that were initiated prior to the execution

of the Genentech Collaboration Agreement at our sole expense. Genentech may access and use any data

generated in these clinical studies.

In addition to the clinical studies included in the global development plan, we may propose certain additional

clinical studies for indications not included in the global development plan, and if the joint development

committee formed by the parties does not elect to include the proposed studies in the global development plan,

then we may conduct the study at our sole expense under certain conditions, and subject to certain restrictions.

Genentech has the option to select any candidate in such studies for potential further joint development and/or

commercialization by Genentech as a Genentech Collaboration Product. In the case that Genentech wishes to

pursue the clinical development of a Genentech Collaboration Product in an indication that we are not interested

in pursuing, then under certain conditions, we may opt out of the co-funding of such development and

Genentech may continue do so at its own costs, except that we are obligated to repay Genentech’s development

costs in the event that such product subsequently receives regulatory approval.

Genentech has the sole right to commercialize the Genentech Collaboration Products on a worldwide basis, with

all profits and losses from such commercialization to be split equally with us. If we exercise our right to opt out of

sharing equally in future development costs for any Genentech Collaboration Products, then we will no longer

split all such profits and losses for such Genentech Collaboration Products equally with Genentech and will

instead receive a royalty on annual worldwide net sales of such Genentech Collaboration Products that are

covered by a valid claim included in certain of our patents and certain joint patents that arise out of the

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collaboration. Furthermore, for certain Genentech Collaboration Products for which we share co-promotion rights

with Genentech, we have the option to assume a percentage to be determined of the total sales force in the

United States and certain other countries, including Germany and other major European markets. In addition,

under certain regulatory and other circumstances, we have the right to independently commercialize Genentech

Collaboration Products in indications that the joint development committee declines to pursue and that

Genentech does not subsequently elect to commercialize, provided that we market such Genentech

Collaboration Products under a separate brand and trademark that is approved by the joint commercialization

committee established by the parties as not confusingly similar to the Genentech Collaboration Products being

commercialized by Genentech. Our ability to research, develop, co-promote and/or independently commercialize

Genentech Collaboration Products may be terminated or limited in the event we undergo a change of control.

We granted to Genentech an exclusive license under certain of our intellectual property, and our interest in any

jointly-owned intellectual property developed under this agreement, to research, develop, make, sell and import

any pharmaceutical products that comprise neoepitope RNA. Genentech granted to us an exclusive, non-

transferable, sublicensable licenses under certain Genentech intellectual property, our intellectual property

exclusively licensed to Genentech, and their interest in any jointly-owned intellectual property developed under

this agreement for the performance of our ongoing clinical studies and the exercise of our rights and obligations

under the Genentech Collaboration Agreement.

Until the first marketing approval for a Genentech Collaboration Product, we have granted Genentech the first

right to negotiate an exclusive license to develop, manufacture and commercialize combination therapies

involving pharmaceutical products based on neoepitope RNA and pharmaceutical products based on non-

neoepitope RNA for the treatment of cancer in humans.

The Genentech Collaboration Agreement will remain in effect so as long as Genentech Collaboration Products

are in development or commercialization, or until the date of the expiration of the last royalty term if BioNTech

has exercised its option to opt-out of joint development of Genentech Collaboration Products. If the agreement

expires, the licenses granted to Genentech become fully-paid up, royalty-free and irrevocable. Genentech may

terminate the Collaboration Agreement if we fail to achieve certain milestone targets or at any time for

convenience with or without reason upon 60 days’ prior written notice. In the event of any such termination, all

rights to the development and commercialization of Genentech Collaboration Products developed under the

collaboration would revert to us and Genentech would grant us licenses under its intellectual property to further

develop and commercialize Genentech Collaboration Products. We would be required to pay certain royalties to

Genentech for such license(s). In addition, either party may terminate the agreement upon the other party’s

uncured material breach or insolvency.

Manufacturing Development and Supply Agreement

Concurrent with the Genentech Collaboration Agreement, we entered into a Manufacturing Development and

Supply Agreement with Genentech and F. Hoffman-La Roche Ltd, or the Genentech Manufacturing Agreement,

which governs the manufacturing, related manufacturing development activities and supply of Genentech

Collaboration Products. Pursuant to the Genentech Manufacturing Agreement, we are responsible for clinical

manufacturing and supply, for developing and implementing manufacturing processes (including pursuant to

specified target turnaround times), and for constructing, commissioning, qualifying and obtaining permits for the

clinical facilities. We are permitted to subcontract certain steps in the clinical manufacturing process to our

affiliate, BioNTech IMFS.

In addition, we are responsible for developing the commercial manufacturing process, which requires more

stringent turnaround times than the clinical manufacturing process. Genentech will generally be responsible for

conducting commercial manufacturing. We are obligated to use commercially reasonable efforts to achieve

certain predetermined clinical manufacturing capacity commitments.

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Under the Genentech Manufacturing Agreement, we and Genentech will jointly develop a manufacturing network

plan detailing the location, capacity, scale-out, associated timing and other appropriate details of the commercial

manufacturing facilities. We may participate in commercial manufacturing through our right to include as part of

the commercial manufacturing network one of our own facilities in the European Union or the United States and

one of our own facilities in another region to be agreed upon with Genentech (provided that in each region our

facility is not the first facility to be included in the commercial manufacturing network).

D. Genmab Next-generation Immunomodulator Collaboration

On May 19, 2015, we entered into a License and Collaboration Agreement with Genmab, which was

subsequently amended and supplemented by side letters, to jointly research, develop and commercialize

polypeptide-based bispecific antibodies against certain target combinations for the treatment of cancer

worldwide, or the Genmab Agreement Field, using certain Genmab technology. In connection with our entry into

that License and Collaboration Agreement, Genmab paid us an upfront fee of $10 million. On July 18, 2022, this

agreement was amended and restated by an Amended and Restated License and Collaboration Agreement

(which, as amended, is referred to as the Genmab Agreement).

Under the Genmab Agreement, we and Genmab must use commercially reasonable efforts to research and

develop clinical candidates, including our next-generation checkpoint immunomodulators, with costs split equally

during the research and evaluation phase. Our joint activities in this phase were governed by a research plan,

which was subject to annual review and updates, and which specifies the clinical candidates to be developed.

This research and evaluation phase expired on September 18, 2022.

We and Genmab must use commercially reasonable efforts to develop candidates selected by the joint research

committee, or the LCA Products, through preclinical and clinical development. The preclinical and clinical

development of the LCA Products would be performed pursuant to a development plan to be agreed upon by us

and Genmab, with costs to be split equally. The joint steering committee may designate a third party as a

manufacturer of an LCA Product or of any of its components.

We and Genmab must use commercially reasonable efforts to jointly commercialize all LCA Products and share

equally all expenses and profits arising from such commercialization. We and Genmab, on a product-by-product

basis and at least 12 months prior to the anticipated start of a pivotal clinical trial for an LCA Product, will jointly

designate between the two of us a lead party responsible for establishing the distribution and marketing

operations in each geographical region. Each party would be entitled to equally co-commercialize the products

pursuant to a separately negotiated global commercialization agreement that the parties agree to negotiate.

Unless otherwise agreed by the joint steering committee established under the agreement, Genmab is

responsible for all regulatory actions and shall own all regulatory approvals obtained for the LCA Products.

Genmab is obligated to provide regular updates to us on regulatory activities.

Each party grants to the other party a worldwide, co-exclusive, sublicensable, royalty-free license under certain

of such first party’s intellectual property, including certain patents and know-how, to perform the research under

this agreement and to research, develop, make, import, use and sell LCA Products in the Genmab Agreement

Field pursuant to the terms of the Genmab Agreement. These licenses shall continue on a country-by-country

and product-by-product basis for as long as development or commercialization activities are contemplated under

the Genmab Agreement.

During the preclinical and clinical development phase for any LCA Product, engagement in research and

development activities in the Genmab Agreement Field unilaterally by a party relating to an LCA Product or its

Back-up Candidate or any bispecific antibody which targets the same target combination for which such LCA

Product or Back-up Candidate has been developed would require the other party’s prior written consent.

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Each party has the right to discontinue its participation in the further development and commercialization of an

LCA Product at two points: (i) when an IND submission package has been agreed upon by the parties and (ii)

when the draft clinical trial report from the first Phase 1/2 clinical trial becomes available. The other party may

elect to continue the development and commercialization of the LCA Product or divest its interest in such LCA

Product. If the other party elects to pursue development and commercialization of such LCA Product alone as a

Unilateral Product, at its sole cost and subject to pre-defined milestone and royalty payments and certain

additional pre-defined terms. If the other party wishes to not pursue such continued development and

commercialization on such pre-defined payment and additional terms, then the parties will jointly divest their

interest in such LCA Product to a third party, and if such divestiture fails, the parties will cease all development

and commercialization of such LCA Product.

The Genmab Agreement will remain in effect until the later of (i) the expiration of the last-to-expire royalty term

for any Unilateral Product or (ii) the time when no LCA Products, Joint Combination Products or Proprietary

Combination Products are being developed or commercialized under this agreement. Either party may terminate

the agreement in its entirety or on a product-by-product basis with immediate effect upon the other party’s

uncured material breach or insolvency.

On August 5, 2022, we and Genmab expanded our global strategic collaboration to develop and commercialize

novel immunotherapies for the treatment of cancer patients. Under this expansion, we and Genmab will jointly

work to research, develop and commercialize novel monospecific antibody candidates for various cancer

indications.

E. OncoC4 Collaboration

On March 17, 2023, we and OncoC4 entered into a License and Collaboration Agreement, or the OncoC4

Agreement, for the license, development and commercialization of ONC-392 and all other monoclonal anti-

CTLA4 antibodies owned or controlled by OncoC4 (referred to as OncoC4 Licensed Compounds) as of the

execution date, including development of combinations of such antibody with other products, for use in humans

or animals, or the OncoC4 Field.

OncoC4 granted us an exclusive license under ONC-392 and OncoC4’s interest in joint intellectual property to

exploit OncoC4 Licensed Compounds and any pharmaceutical or biologic product containing OncoC4 Licensed

Compound (referred to as OncoC4 Licensed Products) in the OncoC4 Field in the entire world, which we refer to

as the OncoC4 Territory. Furthermore, OncoC4 granted us an exclusive option that ended June 30, 2024 to

license AI-061, which is a biopharmaceutical composition containing as its sole active ingredients both ONC-392

and an anti-PD-1 antibody. OncoC4 retains all rights to the anti-PD-1 antibody outside of the combination with

ONC-392.

We agreed to collaborate on research, development, and commercialization of ONC-392 in the OncoC4 Territory

and to use commercially reasonable efforts to conduct development activities of OncoC4 Licensed Compounds

and OncoC4 Licensed Products either as a monotherapy or in combination with an anti-PD-(L)1 antibody and/or

standard of care product (which we refer to collectively as the Mono/PD-1/SOC Combinations) in accordance

with a joint clinical development plan which is governed by a joint steering committee. All costs associated with

the joint development responsibilities are shared equally between us and OncoC4.

We are solely responsible for all development activities for the OncoC4 Licensed Compounds and OncoC4

Licensed Products in any other form or combination other than the Mono/PD-1/SOC Combinations (we refer to

such other combinations as OncoC4 Other Combinations) at our own expense and in accordance with a

research and development plan prepared by us and shared with OncoC4 through the joint steering committee.

We agreed to use commercially reasonable efforts to develop an OncoC4 Licensed Product in at least one

indication for an OncoC4 Other Combination. We agreed to first offer OncoC4 the opportunity to co-fund any

development of a PD-1 Combination prior to pursing such development independently or with a third party.

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We agreed to be solely responsible, at our expense, for commercialization of OncoC4 Licensed Products

worldwide and to use commercially reasonable efforts to commercialize OncoC4 Licensed Products for each

approved indication in certain major markets.

In consideration for the rights granted to us by OncoC4, we made an upfront payment of $200 million, with a

portion of the upfront payment to be used to fund OncoC4’s share of the joint research and development costs

related to ONC-392, and agreed to make potential payments upon the achievement of specified development

and regulatory milestones and upon the achievement of specified sales milestones. We have further agreed to

pay OncoC4 double digit, tiered royalties on annual net sales of OncoC4 Licensed Products during a certain

royalty term starting from launch of product.

The OncoC4 Agreement shall continue until the last-to-expire royalty term in all countries in the OncoC4 Territory

for all OncoC4 Licensed Products. Upon the expiration of the royalty term for an OncoC4 Licensed Product in a

given country in the OncoC4 Territory, the exclusive license granted to us will become a perpetual, irrevocable,

non-exclusive, fully paid-up, and royalty-free license with respect to such OncoC4 Licensed Product in such

country. In addition to termination rights granted to each party in the case of the other party’s uncured material

breach or insolvency, we have the right to terminate the OncoC4 Agreement in its entirety for convenience with

prior written notice to OncoC4.

F. Pfizer COVID-19 Vaccine Collaboration

On April 9, 2020, effective as of March 17, 2020, we entered into a Collaboration Agreement with Pfizer for the

research and development of immunogenic compositions comprising RNA encoding a SARS-CoV-2 polypeptide

or fragment thereof for prophylaxis against SARS-CoV-2 in humans, which we refer to as the Pfizer Corona

Field. On January 29, 2021, effective as of March 17, 2020, we entered into an amended and restated

Collaboration Agreement with Pfizer for the research, development and commercialization of immunogenic

compositions comprising RNA in the Pfizer Corona Field, which we refer to as the Pfizer Agreement.

We and Pfizer agreed to collaborate on research, development and commercialization in the Pfizer Corona Field

worldwide (excluding the Fosun collaboration territory), which we refer to as the Pfizer Collaboration Territory.

The details of such activities are set forth in a research and development plan that is governed by a joint steering

committee. Each party bears its own personnel and capital expenditures costs, but the parties will share the

costs of all other agreed development activities (including the costs of manufacturing material for use in clinical

trials) evenly. Each party will, in good faith, seek funding from government funds, non-governmental

organizations and other third-party organizations to support their research and development activities. Under the

Pfizer Agreement, Pfizer is leading clinical development of and is seeking regulatory approval for any candidates

or products in the United States and we are leading clinical development of and are seeking regulatory approval

for any candidates or products in the European Union, and we will agree on a strategy for all other countries in

the Pfizer Collaboration Territory on an ongoing basis through the joint steering committees.

BioNTech can solely commercialize the vaccine in Germany and Türkiye (collectively referred to as the BioNTech

Commercialization Territory, which is a subset of the Pfizer-Collaboration Territory). We have the option to opt-out

of commercializing the vaccine in Germany and/or Türkiye, whereupon such countries will become part of the

Pfizer Commercialization Territory of the Pfizer Collaboration Territory.

Pfizer has the right to commercialize any approved COVID-19 vaccine in the rest of the Pfizer Collaboration

Territory. On a country-by-country basis in relation to the United Arab Emirates, Southeast Asia, and certain

developing countries, if we obtain funding from a third-party organization that obligates us to commercialize an

approved vaccine in such country, we are obligated to request from Pfizer in writing a decision as to whether

Pfizer wishes to commercialize or distribute such vaccine in such country in accordance with the requirements

agreed with the third-party funder. If Pfizer elects not to commercialize the vaccine in such country, then such

country shall become a part of the BioNTech Commercialization Territory.

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If our Collaboration Agreement with Fosun expires or is otherwise terminated for any reason, as between us and

any international pharmaceutical group headquartered outside of China, we have granted Pfizer a right of first

negotiation to expand the Pfizer Commercialization Territory to include the Fosun Territory.

We and Pfizer share responsibilities for manufacturing and supplying our approved COVID-19 vaccines. If there

is insufficient supply to satisfy the entire demand for vaccines in the Pfizer Collaboration Territory, we and Pfizer

have agreed to determine by mutual consent the allocation of supplies on a fair and equitable basis, subject also

to any applicable law, export controls, and taking into account any government supply obligations, or supply

obligations included in any agreement reached with a third-party funding organization.

Under the Pfizer Agreement, we have granted Pfizer an exclusive, sublicensable license in the Pfizer

Collaboration Territory under certain of our intellectual property, including our patents and know-how, relating to

uridine RNA, modified RNA and replicons in the Pfizer Corona Field as well as certain intellectual property in-

licensed by us from third parties, to use, research, develop, manufacture, commercialize and otherwise exploit

candidates and products selected under the Pfizer Agreement. We undertake to maintain in full effect all

intellectual property licenses held by us at the time we entered into the Pfizer Agreement and not to modify or

amend any such license in a manner that would adversely affect any of the rights granted to Pfizer under the

Pfizer Agreement. We are obligated to notify Pfizer of any breach of our current licenses and may be obligated to

take steps to maintain Pfizer’s access to any intellectual property licensed under such licenses. Under the Pfizer

Agreement, we are obligated to indemnify Pfizer with respect to certain product liability and patent infringement

claims.

During the term of the Pfizer Agreement and a certain period thereafter, we and Pfizer have committed not to

research, develop, manufacture, commercialize or otherwise exploit immunogenic compositions comprising RNA

in the Pfizer Corona Field, or exploit vaccine candidates or products developed under the agreement for any

use, other than pursuant to the Pfizer Agreement, provided, however, that Pfizer shall have the right to work as a

contract manufacturer for a third party and Pfizer shall not be precluded from acquiring a third party, or being

acquired by a third party, that at the time of acquisition is active in the development or commercialization of an

immunogenic composition comprising mRNA in the Pfizer Corona Field.

On April 9, 2020, Pfizer also subscribed for $113 million of our ordinary shares under a separate investment

agreement. In addition, under the Pfizer Agreement, Pfizer made an upfront payment of $72 million and agreed

to make potential payments of up to $563 million upon the achievement of specified regulatory and commercial

milestones. We and Pfizer agreed to share development costs equally. We and Pfizer will share the gross profits

from commercializing a vaccine evenly, as well as the costs for shipping. The Pfizer Agreement continues for so

long as either at least a vaccine is being developed for use in the Pfizer Collaboration Territory or a vaccine is

being commercialized anywhere in the Pfizer Collaboration Territory. In addition to termination rights granted to

each party in the case of the other party’s uncured material breach, Pfizer may terminate the agreement (i) upon

our insolvency or (ii) on a country-by-country basis or in its entirety for convenience upon one (1) year’s prior

written notice provided that any such termination shall not become effective less than two (2) years from the first

commercial sale of an approved vaccine.

IX. Government Regulation

Government authorities in the United States at the federal, state and local levels, and in the European Union and

other countries and jurisdictions, extensively regulate, among other things, the research, development, testing,

manufacture, quality control, approval, packaging, storage, record-keeping, labeling, advertising, promotion,

distribution, marketing, post-approval monitoring and reporting and import and export of pharmaceutical

products, including biological products. In addition, some jurisdictions regulate the pricing of pharmaceutical

products. The processes for obtaining marketing approvals in the United States and in other jurisdictions, along

with subsequent compliance with applicable statutes and regulations and other requirements of regulatory

authorities, require the expenditure of substantial time and financial resources.

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A. Regulation and Procedures Governing Approval of Drug and Biological Products in the United States

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA,

and its implementing regulations and biologics under the FDCA, the Public Health Service Act, or the PHSA, and

their implementing regulations. Both drugs and biologics are subject to other federal, state and local statutes and

regulations. The process of obtaining regulatory approvals and subsequent compliance with applicable federal,

state and local statutes and regulations requires the expenditure of substantial time and financial resources.

Failure to comply with the applicable U.S. requirements at any time during the product development process,

approval process or following approval may subject a sponsor or marketing authorization (BLA/NDA) holder to

administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to

approve pending applications, withdrawal of an approval, license revocation, clinical hold, untitled or warning

letters, voluntary or mandatory product recalls, market withdrawals, product seizures, total or partial suspension

of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and

civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us.

A sponsor seeking approval to market and distribute a new drug or biological product in the United States

generally must satisfactorily complete each of the following steps:

–preclinical laboratory tests, animal studies and formulation studies all performed in accordance with applicable

regulations, including the FDA’s good laboratory practices, or GLP, regulations;

–submission to the FDA of an IND application for human clinical testing, which must become effective before

human clinical trials may begin;

–approval by the IRB representing each clinical site before each clinical trial may be initiated;

–performance of adequate and well-controlled human clinical trials to establish the safety, potency and purity of

the product candidate for each proposed indication, in accordance applicable regulations, including GCP;

–preparation and submission to the FDA of a NDA for a drug product, or a BLA for a biological product

requesting marketing approval for one or more proposed indications, including submission of detailed

information on the manufacture and composition of the product in clinical development, evidence of safety,

purity and potency from preclinical testing and clinical trials, and proposed labeling;

–review of the product by an FDA advisory committee, if applicable;

–satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including

those of third parties, at which the product, or components thereof, are produced to assess compliance with

current GMP requirements and to assure that the facilities, methods and controls are adequate to preserve

the product’s identity, strength, quality and purity;

–satisfactory completion of any FDA audits of the clinical study sites to assure compliance with applicable

regulations and GCP, and the integrity of clinical data in support of the NDA or BLA;

–payment of user fees and securing FDA approval of the NDA or BLA; and

–compliance with applicable regulations post approval, including any post-approval requirements, such as the

potential requirement to implement a REMS and to conduct any post-approval studies required by the FDA.

The preclinical and clinical testing and approval process requires substantial time, effort and financial resources,

and we cannot be certain that any approvals for our product candidates and any future product candidates will

be granted on a timely basis, or at all.

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Preclinical Studies and Investigational New Drug Application

Before testing any drug or biological product candidate in humans, the product candidate must undergo

preclinical testing. Preclinical tests include laboratory evaluations of product chemistry, formulation and stability,

as well as animal studies to evaluate the potential for activity and toxicity. The conduct of the preclinical tests and

formulation of the compounds for testing must comply with federal regulations and requirements. The results of

the preclinical tests, together with manufacturing information, analytical data, any available clinical data or

literature and a proposed clinical protocol, are submitted to the FDA as part of an IND application. The IND

automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises

concerns or questions about the product or conduct of the proposed clinical trial, including concerns that patients

will be exposed to unreasonable health risks, and places the trial on a clinical hold. In that case, the IND sponsor

and the FDA must resolve any outstanding FDA concerns before the clinical trial can begin.

As a result, submission of the IND may result in the FDA not allowing the trial to commence or not be conducted

on the terms originally specified by the sponsor in the IND. If the FDA raises concerns or questions either during

this initial 30-day period, or at any time during the IND process, it may choose to impose a partial or complete

clinical hold. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization and then

only under terms authorized by the FDA. A clinical hold issued by the FDA may therefore delay either a proposed

clinical study or cause suspension of an ongoing study, until all outstanding concerns have been adequately

addressed and the FDA has notified the company that investigation may proceed. This could cause significant

difficulties in completing planned clinical trials in a timely manner.

The FDA may impose clinical holds on a product candidate at any time before or during clinical trials due to

safety concerns or non-compliance.

Human Clinical Trials in Support of an NDA or a BLA

Clinical trials involve the administration of the investigational product candidate to healthy volunteers or patients

with the disease to be treated under the supervision of qualified principal investigators, generally physicians not

employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the

requirement that all patients provide their informed consent for their participation. Clinical trials are conducted

under study protocols detailing, among other things, the objectives of the study, inclusion and exclusion criteria,

the parameters to be used in monitoring safety, dosing procedures and the effectiveness criteria to be evaluated.

A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part

of the IND.

A sponsor who wishes to conduct a clinical trial outside 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, the

sponsor may submit data from the clinical trial to the FDA in support of the NDA or BLA so long as the clinical

trial is well-designed and well-conducted in accordance with GCP, including review and approval by an

independent ethics committee, and the FDA is able to validate the study data through an onsite inspection, if

necessary.

Further, each clinical trial must be reviewed and approved by an IRB either centrally or individually at each

institution at which the clinical trial will be conducted. The IRB will consider, among other things, clinical trial

design, patient informed consent, ethical factors and the safety of patients. An IRB must operate in compliance

with FDA regulations. The FDA, IRB, or the clinical trial sponsor may suspend or discontinue a clinical trial at any

time for various reasons, including a finding that the clinical trial is not being conducted in accordance with FDA

requirements or that the patients are being exposed to an unacceptable health risk. Clinical testing also must

satisfy extensive GCP rules and the requirements for informed consent. The IRB also approves the form and

content of the informed consent that must be signed by each clinical trial subject or his or her legal

representative and receive periodic reports regarding the investigation from the investigators. Additionally, some

clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor,

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known as a data safety monitoring board or committee, or DSMB. This group may recommend continuation of

the study as planned, changes in study conduct, or cessation of the study at designated check points based on

access to certain data from the study.

Clinical trials typically are conducted in three sequential phases, but the phases may overlap or be combined.

Additional studies may be required after approval.

–Phase 1 clinical trials (or Phase 1) are initially conducted in a limited population to test the product candidate

for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion and

pharmacodynamics in healthy humans or, on occasion, in patients, such as in the case of some products for

severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically

administer to healthy volunteers.

–Phase 2 clinical trials (or Phase 2) are generally conducted in a limited patient population to identify possible

adverse effects and safety risks, preliminarily evaluate the efficacy of the product candidate for specific

targeted indications and determine dose tolerance and optimal dosage. Multiple Phase 2 clinical trials may be

conducted by the sponsor to obtain information prior to beginning larger Phase 3 clinical trials. When a drug is

intended to treat life-threatening or severely debilitating illnesses, and particularly for rare diseases, the FDA

may accept well-controlled Phase 2 clinical trials as adequate to provide sufficient data on the drug’s safety

and effectiveness to support a decision on its approvability for marketing, in which case Phase 3 clinical trials

would not be required.

–Phase 3 clinical trials (or Phase 3) proceed if the Phase 2 clinical trials demonstrate that a certain dose or

dose range of the product candidate is potentially effective and has an acceptable safety profile. Phase 3

clinical trials are undertaken within an expanded patient population, often at geographically dispersed clinical

trial sites, to gather additional information about safety and effectiveness necessary to evaluate the overall

benefit-risk relationship of the product and to provide the basis for product labeling.

In some cases, the FDA may approve an NDA or a BLA for a product candidate but require the sponsor to

conduct additional clinical trials to further assess the product candidate’s safety and/or effectiveness after

approval. Such post-approval trials are typically referred to as Phase 4 clinical trials (or Phase 4). These studies

may be used to gain additional experience from the treatment of patients in the intended therapeutic indication

and to document a clinical benefit in the case of biologics approved under accelerated approval regulations. If

the FDA approves a product while a company has ongoing clinical trials that were not necessary for approval, a

company may be able to use the data from these clinical trials to meet all or part of any Phase 4 clinical trial

requirement or to request a change in the product labeling. Failure to exhibit due diligence with regard to

conducting required Phase 4 clinical trials or to comply with post approval commitments could result in

withdrawal of approval for products.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all

clinical activities, clinical data and clinical trial investigators. Annual progress reports detailing the results of the

clinical trials must be submitted to the FDA. Written IND safety reports must be promptly submitted to the FDA

and the investigators for serious and unexpected adverse events, any findings from other trials, tests in

laboratory animals or in vitro testing that suggest a significant risk for patients, or 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 submit an IND safety report within 15 calendar days after the sponsor determines

that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-

threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the

information. The FDA or the sponsor or its DSMB may suspend a clinical trial at any time on various grounds,

including a finding that the patients are being exposed to an unacceptable health risk. Similarly, an IRB can

suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in

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accordance with the IRB’s requirements or if the new drug candidate or biological product candidate has been

associated with unexpected serious harm to patients.

There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results

to public registries. Sponsors of clinical trials of FDA-regulated products, including biologics, are required to

Information related to the product, patient population, phase of investigation, trial sites and investigators, and

other aspects of the clinical trial is then made public as part of the registration. Sponsors are also obligated to

discuss the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed

until the new product or new indication being studied has been approved.

Compliance with GMP Requirements

Before approving an NDA or a BLA, 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 full compliance with GMP requirements and adequate to assure consistent production of the

product within required specifications. Among other things, the sponsor must develop methods for testing the

identity, strength, quality, potency and purity of the final drug or biological product. Additionally, appropriate

packaging must be selected and tested, and stability studies must be conducted to demonstrate that the drug or

biological product does not undergo unacceptable deterioration over its shelf life. In particular, the PHSA

emphasizes the importance of manufacturing control for products like biologics whose attributes cannot be

precisely defined.

Manufacturers and others involved in the manufacture and distribution of drugs and biological products must

also register their establishments with the FDA and certain state agencies. Both domestic and foreign

manufacturing establishments must register and provide additional information to the FDA upon their initial

participation in the manufacturing process.

The manufacturing facilities may be subject to periodic announced and unannounced inspections by government

authorities to ensure compliance with GMPs and other laws. Manufacturers may have to provide, on request,

electronic or physical records regarding their establishments. Delaying, denying, limiting or refusing inspection

by the FDA may lead to a product being deemed to be adulterated.

Review and Approval of an NDA or a BLA

The results of product candidate development, preclinical testing and clinical trials, including negative or

ambiguous results as well as positive findings, are submitted to the FDA as part of an NDA or a BLA requesting a

license to market the product. These applications must contain extensive manufacturing information and detailed

information on the composition of the product and proposed labeling. The FDA adjusts the Prescription Drug

User Fee Act, or 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 or BLAs for products designated as orphan drugs, unless the

product also includes a non-orphan indication.

The FDA has 60 days after submission of the application to conduct an initial review to determine whether the

NDA or BLA is sufficient to accept for filing based on the agency’s threshold determination that it is substantially

complete so as to permit substantive review. Once the submission has been accepted for filing, the FDA begins

an in-depth review of the application. Under the goals and policies agreed to by the FDA under PDUFA, the FDA

aims to complete its initial review of a standard application and respond to the sponsor within ten months of the

60-day filing date, and for a priority review application within six months. The FDA does not always meet its

PDUFA goal dates for standard and priority NDA or BLA applications, and its review goals are subject to change

from time to time. The review process may often be significantly extended by FDA requests for additional

information or clarification. The review process and the PDUFA goal date may also be extended by three months

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if the FDA requests or if the sponsor otherwise provides additional information or clarification regarding

information already provided in the submission within the last three months before the PDUFA goal date.

The FDA reviews NDA and BLA applications to determine, among other things, whether the proposed product is

safe and potent, and/or effective, for its intended use, and has an acceptable purity profile, and whether the

product is being manufactured in accordance with GMP requirements to assure and preserve the product’s

identity, safety, strength, quality, potency and purity. On the basis of the FDA’s evaluation of the application and

accompanying information, including the results of the inspection of the manufacturing facilities and any FDA

audits of clinical trial sites to assure compliance with GCPs, the FDA may issue either an approval letter or a

complete response letter. An approval letter authorizes commercial marketing of the product with specific

prescribing information for specific indications. Under the FDCA, the FDA may approve an NDA if it determines

that the product is safe and effective for its intended use, the benefits of the drug outweigh any risks, and the

methods used in manufacturing the drug and the controls used to maintain the drug’s quality are adequate to

preserve the drug’s identity, strength, quality and purity. Under the PHSA, the FDA may approve a BLA if it

determines that the product is safe, pure and potent and the facility where the product will be manufactured

meets standards designed to ensure that it continues to be safe, pure and potent. If the application is not

approved, the FDA may issue a complete response letter, which will contain the conditions that must be met in

order to secure final approval of the application, and when possible will outline recommended actions the

sponsor might take to obtain approval of the application. If a complete response letter is issued, the sponsor may

either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the

application.

Sponsors that receive a complete response letter who elect to address the deficiencies may submit to the FDA

information that represents a complete response to the issues identified by the FDA in the response letter. Such

resubmissions are classified under PDUFA as either Class 1 or Class 2, based on the information submitted by a

sponsor in response to an action letter. Under the goals and policies agreed to by the FDA under PDUFA, the

FDA aims to review and act on a Class 1 resubmission with two months of receipt and, with respect to a Class 2

resubmission, within six months of receipt. The FDA will not approve an application until issues identified in the

complete response letter have been addressed.

The FDA may also refer the application to an Advisory Committee for review, evaluation and recommendation as

to whether the application should be approved and under what conditions. In particular, the FDA may refer

applications for novel drug or biological products or drug or biological products that present difficult questions of

safety or efficacy to an advisory committee. Typically, an Advisory Committee is a panel of independent experts,

including clinicians and other scientific experts. The FDA is not bound by the recommendations of an Advisory

Committee, but it considers such recommendations carefully when making decisions.

If the FDA approves a new product, it may limit the approved indications for use of the product or limit the

approval to specific dosages. It may also require that certain contraindications, warnings or precautions be

included in the product labeling. In addition, the FDA may call for post-approval studies, including Phase 4

clinical trials, to further assess the product’s safety after approval. The agency may also require testing and

surveillance programs to monitor the product after commercialization, or impose other conditions, including

distribution restrictions or other risk management mechanisms, including risk evaluation and mitigation

strategies, or REMS, to help ensure that the benefits of the product outweigh the potential risks. REMS can

include medication guides, communication plans for healthcare professionals, and elements to assure safe use,

or ETASU. ETASU can include, but are not limited to, special training or certification for prescribing or

dispensing, dispensing only under certain circumstances, special monitoring and the use of patent registries. If

the FDA concludes a REMS is needed, the sponsor of the NDA or BLA must submit a proposed REMS; the FDA

will not approve the NDA or BLA without a REMS, if required. The FDA may prevent or limit further marketing of

a product based on the results of post-marketing studies or surveillance programs. After approval, many 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.

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Fast Track, Breakthrough Therapy and Priority Review Designations

The FDA may designate certain products for expedited review if they are intended to address an unmet medical

need in the treatment of a serious or life-threatening disease or condition. These programs include fast track

designation, breakthrough therapy designation and priority review designation.

The FDA may designate a product for fast track review if it is intended, whether alone or in combination with one

or more other products, for the treatment of a serious or life-threatening disease or condition, and it

demonstrates the potential to address unmet medical needs for such disease or condition. Fast track designation

applies to the combination of the product and the specific indication for which it is being studied. The sponsor of

a new drug or biologic may request that the FDA designate the drug or biologic as a fast track product at any

time during the clinical development of the product. For fast track products, sponsors may have greater

interactions with the FDA and the FDA may initiate review of sections of a fast track product’s application before

the application is complete. This rolling review may be available if the FDA determines, after preliminary

evaluation of clinical data submitted by the sponsor, that a fast track product may be effective. The sponsor must

also provide, and the FDA must approve, a schedule for the submission of the remaining information and the

sponsor must pay applicable user fees. However, the FDA’s time period goal for reviewing a fast track

application does not begin until the last section of the application is submitted, and designation as a fast track

product does not guarantee a decision by that goal date. Fast track designation may be withdrawn by the FDA if

the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

A product may be designated as a breakthrough therapy if it is intended, either alone or in combination with one

or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical

evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or

more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

The FDA may take certain actions with respect to breakthrough therapies, including holding additional meetings

with the sponsor throughout the development process; providing timely advice to the product sponsor regarding

development and approval; involving more senior staff in the review process; assigning a cross-disciplinary

project lead for the review team; and taking other steps to facilitate the design of clinical trials in an efficient

manner.

The FDA may designate a product for priority review if it is a product that treats a serious condition and, if

approved, would provide a significant improvement in safety or effectiveness. The FDA determines, on a case-

by-case basis, whether the proposed product represents a significant improvement when compared with other

available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the

treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented

enhancement of patient compliance that may lead to improvement in serious outcomes and evidence of safety

and effectiveness in a new subpopulation. A priority designation is intended to direct overall attention and

resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing

application to six months (compared to 10 months under standard review). A designation of priority review does

not guarantee a decision by the priority review date.

Fast track designation, priority review and breakthrough therapy designation may expedite the development or

approval process, but do not change the standards for approval.

Accelerated Approval Pathway

The FDA may grant accelerated approval to a product for a serious or life-threatening condition that provides

meaningful therapeutic advantage to patients over existing treatments based upon a determination that the

product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The FDA may

also grant accelerated approval for such a condition when the product has an effect on an intermediate clinical

endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, or IMM, and that is

reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity or

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prevalence of the condition and the availability or lack of alternative treatments. Products granted accelerated

approval must meet the same statutory standards for safety and effectiveness as those granted traditional

approval.

For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement,

radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a

measure of clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than clinical

endpoints. An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered

reasonably likely to predict the clinical benefit of a product, such as an effect on IMM. The FDA has stated that

although it has limited experience with accelerated approvals based on intermediate clinical endpoints, such

endpoints generally may support accelerated approval where the therapeutic effect measured by the endpoint is

not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic

effect is reasonably likely to predict the ultimate clinical benefit of a product.

The accelerated approval pathway is most often used in settings in which the course of a disease is long and an

extended period of time is required to measure the intended clinical benefit of a product. Thus, accelerated

approval has been used extensively in the development and approval of products for treatment of a variety of

cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of

the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or survival

benefit.

The accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent

manner, additional post-approval confirmatory studies to verify and describe the product’s clinical benefit. As a

result, a product candidate approved on this basis is subject to rigorous post-marketing compliance

requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the

clinical endpoint. Failure to conduct required post-approval studies, or to confirm a clinical benefit during post-

marketing studies, may lead the FDA to withdraw the product from the market under expedited withdrawal

procedures applicable to products approved under accelerated approval. All promotional materials for product

candidates approved under accelerated regulations are subject to prior review by the FDA.

Accelerated approval pathways are available for regenerative medicine therapies that meet certain conditions.

Regenerative medicine therapies include cell therapies (both allogeneic and autologous), therapeutic tissue

engineering products, human cell and tissue products, and combination products using any such therapies or

products, except those regulated under section 361 of the PHSA. Human gene therapies, including genetically

modified cells, that lead to a sustained effect on cells or tissues, may also meet the definition of a regenerative

medicine therapy, as may xenogeneic cell products.

Regenerative medicine therapies designed to treat, modify, reverse or cure serious conditions are eligible for

FDA’s expedited programs, including fast track designation, breakthrough therapy designation, priority review

and accelerated approval, if they meet the criteria for such programs. They may also be eligible for Regenerative

Medicine Advanced Therapy Designation, or RMAT designation.

An investigational drug is eligible for RMAT designation if it meets the definition of regenerative medicine

therapy, it is intended to treat, modify, reverse or cure a serious condition, and preliminary clinical evidence

indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such

condition. An unmet medical need is a condition whose treatment or diagnosis is not addressed adequately by

available therapy.

RMAT designation confers all the benefits of the fast track and breakthrough therapy designation programs,

including early interactions with the FDA. The FDA reviews each application on a case-by-case basis to

determine whether the clinical evidence is sufficient to support RMAT designation, considering factors such as

the rigor of data collection, the consistency and persuasiveness of the outcomes, the number of patients, and the

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severity, rarity or prevalence of the condition, among other factors. The FDA may decline to grant RMAT

designation if it finds the clinical evidence insufficient.

RMAT designation may expedite the development or approval process, but it does not change the standards for

approval.

Emergency Use Authorizations

The Secretary of Health and Human Services has the authority to authorize unapproved medical products,

including vaccines, to be marketed in the context of an actual or potential emergency that has been designated

by government officials. The COVID-19 pandemic has been designated such a national emergency. After an

emergency has been announced, the Secretary of Health and Human Services may authorize the issuance of,

and the FDA Commissioner may issue, Emergency Use Authorizations, or EUAs, for the use of specific products

based on criteria established by statute, including that the product at issue may be effective in diagnosing,

treating, or preventing serious or life-threatening diseases when there are no adequate, approved, and available

alternatives. An EUA is subject to additional conditions and restrictions and is product-specific. An EUA

terminates when the emergency determination underlying the EUA terminates or full approval is obtained. An

EUA is not a long-term alternative to obtaining FDA approval, licensure, or clearance for a product. FDA may

revoke an EUA where it is determined that the underlying health emergency no longer exists or warrants such

authorization, so it is not possible to predict how long an EUA may remain in place.

Post-Approval Regulation

If regulatory approval for marketing of a product or for a new indication for an existing product is obtained, the

sponsor will be required to comply with rigorous and extensive post-approval regulatory requirements as well as

any post-approval requirements that the FDA has imposed on the particular product as part of the approval

process. The sponsor will be required, among other things, to report certain adverse reactions and

manufacturing problems, or certain other events to the FDA, provide updated safety and efficacy information and

comply with requirements concerning advertising and promotional labeling. Manufacturers and certain of their

subcontractors 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 GMP regulations, which impose certain procedural and documentation

requirements upon manufacturers. Accordingly, the BLA holder and its third-party manufacturers must continue

to expend time, money and effort in the areas of production and quality control to maintain compliance with GMP

regulations and other regulatory requirements. In addition, changes to the manufacturing process or facility

generally require prior FDA approval before being implemented, and other types of changes to the approved

product, such as adding new indications and additional labeling claims, are also subject to further FDA review

and approval.

Once an approval is granted, the FDA may withdraw the 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 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; imposition of post-market study requirements or clinical trial

requirements 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 the product, complete withdrawal of the product from the

market or product recalls;

–fines, untitled letters or warning letters or holds on post-approval clinical trials;

–adverse publicity, including FDA statements regarding the safety of products;

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–refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or

revocation of product license approvals;

–product seizure or detention, or refusal to permit the import or export of products; or

–injunctions, fines, debarment, disgorgement of profits 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. Pharmaceutical 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.

Orphan Drug Designation

Orphan drug designation in the United States is designed to encourage sponsors to develop products intended

for rare diseases or conditions. In the United States, a rare disease or condition is statutorily defined as a

disease or condition that affects fewer than 200,000 individuals in the United States or that affects more than

200,000 individuals in the United States but for which there is no reasonable expectation that the cost of

developing and making available the product for the disease or condition will be recovered from sales of the

product in the United States.

Orphan drug designation qualifies a company for certain financial incentives, including tax advantages and, if the

product receives the first FDA approval for the indication for which it has orphan designation, market exclusivity

for seven years following the date of the product’s marketing approval. An application for designation as an

orphan product can be made any time prior to the filing of an application for approval to market the product.

Once a product receives orphan drug designation from the Office of Orphan Products Development at the FDA,

the product must then go through the review and approval process like any other product.

In addition, a sponsor of a product that is otherwise the same product as an already approved orphan drug may

seek and obtain orphan drug designation for the subsequent product for the same rare disease or condition if it

can present a plausible hypothesis that its product may be clinically superior to the first product. More than one

sponsor may receive orphan drug designation for the same product for the same rare disease or condition, but

each sponsor seeking orphan drug designation must file a complete request for designation.

The period of exclusivity begins on the date that the marketing application is approved by the FDA and applies

only to the indication for which the product has been designated. The FDA may approve a second application for

the same product for a different use or a second application for a clinically superior version of the product for the

same use. The FDA cannot, however, approve the same product made by another manufacturer for the same

indication during the market exclusivity period unless it has the consent of the sponsor, the manufacturer makes

a showing of clinical superiority over the product with orphan exclusivity, or the sponsor is unable to provide

sufficient quantities.

Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review

and approval process.

Pediatric Studies and Exclusivity

Under the Pediatric Research Equity Act of 2003, an NDA or a BLA or supplement thereto must contain data that

are adequate to assess the safety and effectiveness of the product 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. Sponsors who are planning to submit a marketing application for a drug or

biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen

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or new route of administration must also submit pediatric study plans prior to the assessment data, and no later

than 60 calendar days following an end-of-Phase 2 meeting with the FDA or, if there is no such meeting, as early

as practicable before the initiation of the Phase 3 or Phase 2/3 study. Pediatric study plans must contain an

outline of the proposed pediatric study or studies the sponsor plans to conduct, including study objectives and

design, any deferral or waiver requests and other information required by regulation. The sponsor, the FDA, and

the FDA’s internal review committee must then review the information submitted, consult with each other and

agree upon a final plan. The FDA or the sponsor may request an amendment to the plan at any time.

The FDA may, on its own initiative or at the request of the sponsor, grant deferrals for submission of some or all

pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data

requirements. Additional requirements and procedures relating to deferral requests and requests for extension of

deferrals are contained in the Food and Drug Administration Safety and Innovation Act. Unless otherwise

required by regulation, the pediatric data requirements do not apply to products with orphan designation.

Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted,

provides for the attachment of an additional six months of marketing protection to the term of any existing

regulatory exclusivity, including the non-patent and orphan exclusivity. This six-month exclusivity may be granted

if an NDA or a BLA sponsor submits pediatric data that fairly respond to a written request from the FDA for such

data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the

clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of

requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever

statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months.

This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot

approve another application.

Biosimilars and Reference Product Exclusivity

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation

Act, or collectively, the ACA, signed into law in 2010, includes a subtitle called the Biologics Price Competition

and Innovation Act of 2009, or the BPCIA, which created an abbreviated approval pathway for biological

products that are biosimilar to or interchangeable with an FDA-approved reference biological product. To date, a

number of biosimilars have been licensed under the BPCIA, and numerous biosimilars have been approved in

Europe.

Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years

following the date that the reference product was first licensed by the FDA. In addition, the approval of a

biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference

product was first licensed. During this 12-year period of exclusivity, another company may still market a

competing version of the reference product if the FDA approves a full BLA for the competing product containing

that sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the

safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars

approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable”

by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.

The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and

the reference product in terms of safety, purity and potency, can be shown through analytical studies, animal

studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference

product and the product must demonstrate that it can be expected to produce the same clinical results as the

reference product in any given patient and, for products that are administered multiple times to an individual, the

biologic and the reference biologic may be alternated or switched after one has been previously administered

without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

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Complexities associated with the larger, and often more complex, structures of biological products, as well as the

processes by which such products are manufactured, pose significant hurdles to implementation of the

abbreviated approval pathway that are still being worked out by the FDA.

The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, recent

government proposals have sought to reduce the 12-year reference product exclusivity period. Other aspects of

the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent

litigation. As a result, the ultimate implementation and impact of the BPCIA is subject to significant uncertainty.

B. Regulation and Procedures Governing Approval of Medicinal Products in the European Union

The process governing approval of medicinal products, including biological medicinal products and advanced

therapy medicinal products, or ATMPs, which comprise gene therapy products, somatic cell therapy products

and tissue-engineered products, in the European Union generally follows the same lines as in the United States.

It entails satisfactory completion of pharmaceutical development, nonclinical and clinical studies to establish the

safety and efficacy of the medicinal product for each proposed indication. Moreover, an applicant must also

demonstrate the ability to manufacture the product to a suitable quality.

Clinical Trial Approval

Until recently, pursuant to the Clinical Trials Directive 2001/20/EC and the Directive 2005/28/EC on GCP, a

system for the approval of clinical trials in the European Union had been implemented through national

legislation of the member states. Under this system, a sponsor had to obtain approval from the competent

national authority of a European Union member state in which the clinical trial is to be conducted or in multiple

member states if the clinical trial is to be conducted in a number of member states. Furthermore, the sponsor

could only start a clinical trial at a specific study site after an independent ethics committee had issued a

favorable opinion.

In April 2014, the European Union adopted a new Clinical Trials Regulation (EU) No 536/2014, which took effect

on January 31, 2022 and replaced the Clinical Trials Directive 2001/20/EC. Commission Implementing

Regulation (EU) 2017/556 replaced the GCP Directive 2005/28/EC. The Clinical Trials Regulation has

overhauled the former system of approvals. Specifically, the Regulation, which is directly applicable in all

member states, aims to simplify and streamline the approval of clinical trials in the European Union. For

instance, Regulation (EU) No 536/2014 enables sponsors to submit one online application via a single online

platform known as the Clinical Trials Information System (CTIS) for approval to run a clinical trial in several

European countries, making it more efficient to carry out such multinational trials. It provides for strictly defined

deadlines for the assessment of clinical trial applications. This means that one national authority takes the lead

in reviewing the application and the other national authorities have only limited involvement, although the clinical

trial approval is still granted by each national competent authority. Any substantial changes to the trial protocol or

other information submitted with the clinical trial applications must be notified to or approved by the relevant

competent authorities and ethics committees.

As of January 31, 2025, all new or ongoing clinical trials in the European Union are subject to the requirements

of the Clinical Trials Regulation (and the Clinical Trial Directive no longer applies).

Clinical trials must be conducted in accordance with European Union and national regulations and the

International Conference on Harmonization, or ICH, guidelines on GCP. Additional GCP guidelines from the

European Commission, with a focus on traceability, apply to clinical trials of ATMPs. If the sponsor of the clinical

trial is not established within the European Union, it must appoint an entity within the European Union to act as

its legal representative.

The clinical trial application must be accompanied by a copy of the trial protocol and an investigational medicinal

product dossier with supporting information prescribed by applicable legislation as further detailed in applicable

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guidance documents. Moreover, the sponsor must take out a clinical trial insurance policy, and in most European

Union countries the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical

trial.

The sponsor of a clinical trial must register the clinical trial in advance, and information related to the product,

patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial will

be made public as part of the registration. The results of the clinical trial must be submitted to the competent

authorities and, with the exception of non-pediatric Phase 1 trials, will be made public at the latest within 12

months after the end of the trial.

During the development of a medicinal product, the European Medicines Agency, or EMA, and national

medicines regulators within the European Union provide the opportunity for dialogue and guidance on the

development program. At the EMA level, this is usually done in the form of scientific advice, which is given by the

Scientific Advice Working Party of the Committee for Medicinal Products for Human Use, or CHMP. A fee is

incurred with each scientific advice procedure. Advice from the EMA is typically provided based on questions

concerning, for example, quality (chemistry, manufacturing and controls testing), nonclinical testing and clinical

studies, and pharmacovigilance plans and risk-management programs. Advice is not legally binding with regard

to any future marketing authorization application of the product concerned.

Marketing Authorization

To obtain a marketing authorization for a product under the European Union regulatory system, a sponsor must

submit a marketing authorization application, or MAA, either under the centralized procedure administered by the

EMA or one of the procedures administered by competent authorities in European Union member states

(decentralized procedure, mutual recognition procedure, or if the product is to be approved in only one member

state, the national procedure).

All application procedures require an application in the common technical document, or CTD, format, which

includes the submission of detailed information about the manufacturing and quality of the product, and

nonclinical and clinical trial information. There is an increasing trend in the European Union toward greater

transparency and, while certain of the manufacturing or quality information is currently generally protected as

commercially confidential information, the EMA and national regulatory authorities are now liable to disclose

much of the nonclinical and clinical information in marketing authorization dossiers, including the full clinical

study reports, in response to freedom of information requests after the marketing authorization has been

granted. In October 2014, the EMA adopted a policy under which clinical study reports would be posted on the

agency’s website following the grant, denial or withdrawal of a MAA, subject to procedures for limited redactions

and protection against unfair commercial use. The full operation of this policy has been suspended in recent

years due to priorities. However, it continues to apply the policy to COVID-19 vaccines and therapeutics and any

medicines with new active substances that received a CHMP opinion from September 2023 onwards or were

withdrawn before the opinion stage. A similar transparency requirement is contained in the Clinical Trials

Regulation (EU) No 536/2014.

A marketing authorization may be granted only to a sponsor established in the European Union. Regulation (EC)

No. 1901/2006 on medicinal products for pediatric use provides that prior to obtaining a marketing authorization

in the European Union in the centralized procedure, a sponsor must demonstrate compliance with all measures

included in an EMA-approved Pediatric Investigation Plan covering all subsets of the pediatric population, unless

the EMA has granted a product-specific waiver, class waiver or deferral for one or more of the measures

included in the Pediatric Investigation Plan.

The centralized procedure provides for the grant of a single marketing authorization by the European

Commission that is valid for all European Union and European Economic Area member states. Pursuant to

Regulation (EC) No. 726/2004, the centralized procedure is compulsory for specific products, including for

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medicines (including vaccines) produced by certain biotechnological processes, products designated as orphan

medicinal products, advanced therapy medicinal products and products with a new active substance indicated

for the treatment of certain diseases, including products for the treatment of cancer. For products with a new

active substance indicated for the treatment of other diseases and products that are highly innovative or for

which a centralized process is in the interest of patients, the centralized procedure is optional.

Under the centralized procedure, the CHMP established at the EMA is responsible for conducting the

assessment of a product to define its risk/benefit profile. Under the centralized procedure, the maximum

timeframe for the evaluation of an MAA is 210 days, excluding clock stops when additional information or written

or oral explanation is to be provided by the applicant in response to questions from the CHMP. Accelerated

evaluation may be granted by the CHMP in exceptional cases, when a medicinal product is of major interest

from the point of view of public health determined by three cumulative criteria: (i) the seriousness of the disease

(e.g., heavy disabling or life-threatening diseases) to be treated, (ii) the absence or insufficiency of an

appropriate alternative therapeutic approach, and (iii) anticipation of high therapeutic benefit.

If the CHMP accepts such a request, the time limit of 210 days will be reduced to 150 days, but it is possible that

the CHMP may revert to the standard time limit for the centralized procedure if it determines that it is no longer

appropriate to conduct an accelerated assessment. The Committee for Advanced Therapies, or CAT, is

responsible in conjunction with the CHMP for the evaluation of ATMPs. The CAT is primarily responsible for the

scientific evaluation of ATMPs and prepares a draft opinion on the quality, safety and efficacy of each ATMP for

which a MAA is submitted. The CAT’s opinion is then taken into account by the CHMP when giving its final

recommendation regarding the authorization of a product in view of the balance of benefits and risks identified.

Although the CAT’s draft opinion is submitted to the CHMP for final approval, the CHMP may depart from the

draft opinion if it provides detailed scientific justification. The CHMP and CAT are also responsible for providing

guidelines on ATMPs and have published numerous guidelines, including specific guidelines on gene therapies

and cell therapies. These guidelines, which are not legally binding, provide additional guidance on the factors

that the EMA will consider in relation to the development and evaluation of ATMPs and include, inter alia, the

preclinical studies required to characterize ATMPs, the manufacturing and control information that should be

submitted in a MAA; and post-approval measures required to monitor patients and evaluate the long term

efficacy and potential adverse reactions of ATMPs.

The European Commission may grant a so-called “marketing authorization under exceptional circumstances.”

Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide

comprehensive data on the efficacy and safety under normal conditions of use, because the indications for which

the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected

to provide comprehensive evidence, or in the present state of scientific knowledge, comprehensive information

cannot be provided, or it would be contrary to generally accepted principles of medical ethics to collect such

information. Consequently, marketing authorization under exceptional circumstances may be granted subject to

certain specific obligations, which may include the following:

–the applicant must complete an identified program of studies within a time period specified by the competent

authority, the results of which form the basis of a reassessment of the benefit/risk profile;

–the medicinal product in question may be supplied on medical prescription only and may in certain cases be

administered only under strict medical supervision, possibly in a hospital, and in the case of a radio-

pharmaceutical, by an authorized person; and

–the package leaflet and any medical information must draw the attention of the medical practitioner to the fact

that the particulars available concerning the medicinal product in question are as yet inadequate in certain

specified respects.

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A marketing authorization under exceptional circumstances is subject to annual review to reassess the risk-

benefit balance in an annual re-assessment procedure. Continuation of the authorization is linked to the annual

reassessment and a negative assessment could potentially result in the marketing authorization being

suspended or revoked. The renewal of the marketing authorization of a medicinal product under exceptional

circumstances follows the same rules as a “normal” marketing authorization. After five years, the marketing

authorization will then be renewed under exceptional circumstances for an unlimited period, unless the EMA

decides, on justified grounds, to proceed with one additional five-year renewal.

The European Commission may also grant a so-called “conditional marketing authorization” prior to obtaining the

comprehensive clinical data required for an application for a full marketing authorization. Such conditional

marketing authorizations may be granted for product candidates (including medicines designated as orphan

medicinal products and vaccines) if the CHMP finds that all the following requirements are met:

–the benefit-risk balance of the product is positive;

–it is likely that the applicant will be able to provide comprehensive data;

–unmet medical needs will be fulfilled; and

–the benefit to public health of the medicinal product’s immediate availability on the market outweighs the risks

due to need for further data.

A conditional marketing authorization will contain specific obligations to be fulfilled by the marketing authorization

holder, including obligations with respect to the completion of ongoing or new studies, manufacturing information

and with respect to the collection of pharmacovigilance data. Conditional marketing authorizations are valid for

one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of

the need for additional or modified conditions and/or specific obligations. The timelines for the centralized

procedure described above also apply with respect to the review by the CHMP of applications for a conditional

marketing authorization. Once comprehensive data on the medicinal product have been obtained, the marketing

authorization may be converted into a standard marketing authorization which is no longer subject to specific

obligations. Initially, this is valid for five years, but can be renewed for unlimited validity.

During the COVID-19 pandemic, the EMA followed a “rolling review” process for COVID-19 vaccines, which is an

ad hoc procedure by which data is assessed as it becomes available with the aim of granting a conditional

marketing authorization.

The European Union medicines rules expressly permit the member states to adopt national legislation prohibiting

or restricting the sale, supply or use of any medicinal products containing, consisting of or derived from a specific

type of human or animal cell, such as embryonic stem cells.

Periods of Authorization and Renewals

A marketing authorization is valid for five years, in principle, and it may be renewed after five years on the basis

of a reevaluation of the risk benefit balance by the EMA or by the competent authority of the authorizing member

states. To that end, the marketing authorization holder must provide the EMA or the competent authority with a

consolidated version of the file in respect of quality, safety and efficacy, including all variations introduced since

the marketing authorization was granted, at least six months before the marketing authorization ceases to be

valid. Once renewed, the marketing authorization is valid for an unlimited period, unless the European

Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed

with one additional five-year renewal period. Any authorization that is not followed by the placement of the

product on the European Union market (in the case of the centralized procedure) or on the market of the

authorizing member state within three years after authorization ceases to be valid (referred to as the “sunset”

clause).

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Emergency Use Distribution

The European Union medicines rules, as implemented into the national laws of the EU member states, permit

national authorities to authorize temporarily the distribution of an unapproved medicinal product in certain

emergency situations, including suspected or confirmed spread of pathogenic agents. Such an emergency use

distribution, or EUD (sometimes referred to as a “temporary exemption,” i.e., a temporary exemption from the

requirement to obtain a marketing authorization), would apply for the duration of the emergency only and would

be limited to the member state in which it has been issued. When considering whether to grant an EUD, the

relevant member state decides, which data it requires for the grant of the EUD. COVID-19 vaccines to date have

followed the centralized procedure, which was previously combined with a rolling review of data with a view to

granting conditional marketing authorizations.

Regulatory Requirements after Marketing Authorization

Following approval, the holder of the marketing authorization is required to comply with a range of requirements

applicable to the manufacturing, marketing, promotion and sale of the medicinal product. These include

compliance with the European Union’s stringent pharmacovigilance or safety reporting rules, pursuant to which

post-authorization studies and additional monitoring obligations can be imposed. The holder of a marketing

authorization must establish and maintain a pharmacovigilance system and appoint an individual qualified

person for pharmacovigilance who is responsible for oversight of that system. Key obligations include expedited

reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

All new MAAs must include a risk management plan, or RMP, describing the risk management system that the

company will put in place and documenting measures to prevent or minimize the risks associated with the

product. The regulatory authorities may also impose specific obligations as a condition of the marketing

authorization. Such risk-minimization measures or post-authorization obligations may include additional safety

monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization

safety or efficacy studies. RMPs and PSURs are routinely available to third parties requesting access, subject to

limited redactions.

In addition, the manufacturing of authorized products, for which a separate manufacturer’s license is mandatory,

must also be conducted in strict compliance with the EMA’s GMP requirements and comparable requirements of

other regulatory bodies in the European Union, which mandate the methods, facilities and controls used in the

manufacturing, processing and packing of products to assure their safety and identity. Specifically, medicinal

products may only be manufactured in the European Union, or imported into the European Union from another

country, by the holder of a manufacturing/import authorization from the competent national authority. The

manufacturer or importer must have a qualified person who is responsible for certifying that each batch of

product has been manufactured in accordance with European Union standards of good manufacturing practice,

or GMP, before releasing the product for commercial distribution in the European Union or for use in a clinical

trial. Manufacturing facilities are subject to periodic inspections by the competent authorities for compliance with

GMP.

Finally, the marketing and promotion of authorized products, including industry-sponsored continuing medical

education and advertising directed toward the prescribers of products and/or the general public, are strictly

regulated in the European Union. In principle, all advertising and promotional activities for the product must be

consistent with the approved summary of product characteristics, and therefore all off-label promotion is

prohibited. Direct-to-consumer advertising of prescription medicines (including vaccines) is also prohibited in the

European Union. Although general requirements for advertising and promotion of medicinal products are

established under Directive 2001/83/EC, as amended, the details and the enforcement of these rules are

governed by regulations in each member state and can differ from one country to another.

The enforcement actions and consequences for non-compliance with the EU legislation are similar to those

listed above for the United States. For centrally approved products in the EU, there is the possibility of fines for

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regulatory non-compliance with certain of the legal requirements, including in relation to obligations regarding

placing the product on the market, safety monitoring and pediatric compliance.

Human Cells and Tissues

Human cells and tissues that are intended for human applications but that do not fall within the scope of rules

governing medicinal products or medical devices are not subject to premarket review and approval, nor do they

require extensive preclinical and clinical testing. However, there are European Union rules governing the

donation, procurement, testing and storage of human cells and tissues intended for human application, whether

or not they are ATMPs. These rules also cover the processing, preservation and distribution of human cell and

tissues that are not ATMPs. Establishments that conduct such activities must be licensed and are subject to

inspection by regulatory authorities. Such establishments must implement appropriate quality systems and

maintain appropriate records to ensure that cells and tissues can be traced from the donor to the recipient and

vice versa. There are also requirements to report serious adverse events and reactions linked to the quality and

safety of cells and tissues. More detailed rules may exist at the national level.

Named Patient Supplies and Compassionate Use Programs

The European Union medicines rules allow individual member states to permit the supply of a medicinal product

without a marketing authorization to fulfill special needs, where the product is supplied in response to a bona fide

unsolicited order, formulated in accordance with the specifications of a healthcare professional and for use by an

individual patient under his direct personal responsibility. This may in certain countries also apply to products

manufactured in a country outside the European Union and imported to treat specific patients or small groups of

patients.

Some member state laws also provide for compassionate use on a “cohort” basis, subject to review and

approval of the cohort program based on the local laws in the member state.

Orphan Drug Designation and Exclusivity

Regulation (EC) No. 141/2000 and Regulation (EC) No. 847/2000 provide that a product can be designated as

an orphan drug by the European Commission if its sponsor can establish: that the product is intended for the

diagnosis, prevention or treatment of (i) a life-threatening or chronically debilitating condition affecting not more

than five in 10,000 persons in the European Union when the application is made, or (ii) a life-threatening,

seriously debilitating or serious and chronic condition in the European Union and that without incentives it is

unlikely that the marketing of the product in the European Union would generate sufficient return to justify the

necessary investment. For either of these conditions, the sponsor must demonstrate that there exists no

satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in

the European Union or, if such method exists, the product has to be of significant benefit compared to products

available for the condition.

An orphan drug designation provides a number of benefits, including fee reductions, regulatory assistance and

the possibility to apply for a centralized European Union marketing authorization. Marketing authorization for an

orphan drug leads to a 10-year period of orphan market exclusivity. During this orphan market exclusivity period,

neither the EMA nor the European Commission or the member states can accept an application or grant a

marketing authorization for a “similar medicinal product.” A “similar medicinal product” is defined as a medicinal

product containing a similar active substance or substances as contained in a currently authorized orphan

medicinal product, and which is intended for the same therapeutic indication. The market exclusivity period for

the authorized therapeutic indication may, however, be reduced to six years if, at the end of the fifth year, it is

established that the product no longer meets the criteria for orphan drug designation.

European Data Collection and Data Protection Laws

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We are required to comply with strict data protection and privacy legislation in the jurisdictions in which we

operate, including the General Data Protection Regulation (EU) 2016/679, or GDPR. The GDPR governs our

collection and use of personal data in the European Union relating to individuals (e.g., patients). The GDPR

imposes several requirements on organizations that process such data, including: to observe core data

processing principles; to comply with various accountability measures; to provide more detailed information to

individuals about data processing activities; to establish a legal basis to process personal data (including

enhanced consent requirements); to maintain the integrity, security and confidentiality of personal data; and to

report personal data breaches. The GDPR also restricts the transfer of personal data outside of the European

Economic Area (e.g., to the United States and other countries that are not deemed to provide adequate

protection under their domestic laws). The GDPR may impose additional responsibility and liability in relation to

personal data that we process, and require us to put in place additional mechanisms ensuring compliance with

the new data protection rules. This may be onerous and adversely affect our business, financial condition, results

of operations and prospects. Failure to comply with the requirements of the GDPR and related national data

protection laws of European Union member states may result in a variety of enforcement measures, including

significant fines and other administrative measures. The GDPR has introduced substantial fines for breaches of

the data protection rules, increased powers for regulators, enhanced rights for individuals, and new rules on

judicial remedies and collective redress. We may be subject to claims by third parties, such as patients or

regulatory bodies, that we or our employees or independent contractors inadvertently or otherwise breached

GDPR and related data protection rules. Litigation may be necessary to defend against these claims. There is no

guarantee of success in defending these claims, and if we do not prevail, we could be required to pay substantial

fines and/or damages and could suffer significant reputational harm. Even if we are successful, litigation could

result in substantial cost and be a distraction to management and other employees.

C. Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which

we may obtain regulatory approval. Even if our product candidates are approved for marketing, sales of such

product candidates 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 such product candidates. In

the United States, the member states of the European Union 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. Reimbursement rules and levels

are not harmonized in the European Union and therefore differ from member state to member state. Patients are

unlikely to use any product candidates we may develop unless coverage is provided and reimbursement is

adequate to cover a significant portion of the cost of such product candidates. The process for determining

whether a 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 price and examining the medical necessity and cost-effectiveness of medical

products and services and imposing controls to manage costs.

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, and the cost of these studies would be in addition to the costs required to obtain

FDA or other comparable marketing approvals. Even after pharmacoeconomic studies are conducted, product

candidates may not be considered medically necessary or cost effective. A decision by a third-party payor not to

cover any product candidates we may develop could reduce physician utilization of such product candidates

once approved and have a material adverse effect on our sales, results of operations and financial condition.

Additionally, a payor’s decision to provide coverage for a product does not imply that an adequate

reimbursement rate will be approved. For example, the payor may require co-payments that patients find

unacceptably high. Further, one payor’s determination to provide coverage for a product does not assure that

such coverage will continue or that other payors will also provide coverage and reimbursement for the product,

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and the level of coverage and reimbursement can differ significantly from payor to payor. Third-party

reimbursement and coverage may not be adequate to enable us to maintain price levels sufficient to realize an

appropriate return on our investment in product development. The insurance coverage and reimbursement

status of newly approved products for orphan diseases is particularly uncertain, and failure to obtain or maintain

adequate coverage and reimbursement for any such product candidates could limit a company’s ability to

generate revenue.

The containment of healthcare costs also has become a priority of U.S. federal and state and other non-U.S.

governments as well as other third-party payors such as statutory health insurance funds, and the prices of

pharmaceuticals 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 from the sale of any approved products. Coverage policies and third-party 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 marketing approval, less favorable coverage policies and

reimbursement rates may be implemented or coverage may be ended in the future.

Outside the United States, we will face challenges in ensuring and obtaining adequate coverage and payment

for any product candidates we may develop. Pricing of prescription pharmaceuticals is subject to governmental

control in many countries, including in particular the member states of the European Union. Pricing negotiations

with governmental authorities or other third-party payors such as statutory health insurance funds can extend

well beyond the receipt of regulatory marketing approval for a product and may require us to conduct a clinical

trial or non-interventional study that compares the cost effectiveness of any product candidates we may develop

to other available therapies. The conduct of such a clinical trial or study could be expensive and result in delays

in our commercialization efforts.

In the European Union, pricing and reimbursement schemes vary widely from country to country. Some countries

provide that products may be marketed only after a reimbursement price has been agreed. Some countries may

require the completion of additional studies that compare the cost effectiveness of a particular product candidate

to currently available therapies (so called health technology assessments) in order to obtain reimbursement or

pricing approval. The European Union recently adopted Regulation (EU) 2021/2282 on health technology

assessment, which provides a framework for member states to cooperate on health technology assessments at

the EU level. The Regulation is directly applicable in all EU member states which is in a phased period of

applicability since January 12, 2025, although pricing will still be determined nationally. Moreover, at the national

level, European Union member states may restrict the range of products for which their national health insurance

systems provide reimbursement and to control the prices of medicinal products for human use. Member states

may approve a specific price for a product or may instead adopt a system of direct or indirect controls on the

profitability of the company placing the product on the market. Other member states allow companies to fix their

own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit

prescriptions. Recently, many countries in the European Union have increased the amount of discounts required

on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures,

especially in light of the severe fiscal and debt crises experienced by many countries in the European Union. The

downward pressure on health care costs in general, particularly prescription products, has become intense. As a

result, increasingly high barriers are being erected to the entry of new products in the marketplace. Political,

economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations

may continue after reimbursement has been obtained. Reference pricing used by various European Union

member states and parallel trade (arbitrage between low-priced and high-priced member states) can further

reduce prices. Special pricing and reimbursement rules may apply to orphan drugs. Inclusion of orphan drugs in

reimbursement systems tend to focus on the medical usefulness, need, quality and economic benefits to patients

and the healthcare system as for any product. Acceptance of any medicinal product for reimbursement may

come with cost, use and often volume restrictions, which again can vary by country. In addition, results-based

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rules of reimbursement may apply. 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 of our products, if approved in those countries.

For COVID-19 vaccine candidates in the European Union, no pricing and reimbursement or health technology

assessments discussions have taken place with the respective health insurances and competent bodies at a

national member state level. Currently, COVID-19 vaccine candidates are supplied in the European Union based

on vaccine supply agreements with the European Commission that is acting on behalf and in the name of the

member states of the European Union.

D. United Kingdom

Following the UK’s withdrawal from the European Union on January 31, 2020, the Trade and Cooperation

Agreement, or the TCA, which formally entered into force on May 1, 2021, serves as the primary treaty defining

the political and economic relationship between the UK and the European Union after such withdrawal. While the

TCA governs tariff and quota free trade between the United Kingdom and the European Union markets, it does

not provide for regulatory alignment. The regulatory framework for medicinal products in the United Kingdom is

predominantly derived from European Union law. The UK currently offers different routes to obtain a marketing

authorization: (a) a national application route with a 150-day assessment timeline, excluding clock stops or (b)

an international recognition route by which a company relies on a positive CHMP opinion or an approval granted

by another reference regulator, including the FDA and the Japanese PDMA. The international recognition

procedure takes 60 days with no clock stops for simpler applications that were approved by the reference

regulator within the past two years and 110 days with the possibility of a clock stop for all other eligible

applications.

Clinical trial rules in the UK are based on the wording of the previous European Union Clinical Trials Directive

2001/20/EC, although the UK recently updated its legislation governing clinical trials pursuant to the Medicines

for Human Use (Clinical Trials) (Amendment) Regulations 2025. The reforms retain the core requirements of

clinical trial regulation, including the need for both regulatory and ethics committee approval, but introduce

procedural changes such as a combined regulatory and ethics committee review process, streamlined and

accelerated assessments for low intervention clinical trials, and enhanced transparency obligations.

Domestic United Kingdom law provided that all existing European Union law in force on December 31, 2020 was

retained in UK national law, subject to certain revisions that became necessary as a result of Brexit. However,

the Retained EU Law (Revocation and Reform) Act 2023 came into force on January 1, 2024. This revoked

some retained EU laws (although not any relating to medicines regulation). All other retained EU laws have been

renamed as “assimilated laws” and are no longer subject to the EU principles of interpretation. Thus, while at

least initially the United Kingdom and the European Union laws relating to medicines are largely aligned, there is

the potential for further divergence in the future.

Under the terms of the Northern Ireland Protocol to the Withdrawal Agreement, European Union law governing

medicinal products continued to apply to and in Northern Ireland resulting in the potential for separate marketing

authorizations in Great Britain and Northern Ireland. In March 2023, the Northern Ireland Protocol was adjusted

by the Windsor Framework, which is another post-Brexit agreement between the EU and the UK. The Windsor

Framework aims to make it easier to move certain goods, including medicines, from Great Britain to Northern

Ireland. Beginning January 1, 2025, medicines for supply in the UK are now authorized UK-wide by the

Medicines and Healthcare products Regulatory Agency (MHRA) only and companies can no longer apply for, or

maintain, separate licenses for Great Britain and Northern Ireland to market new medicines. Other key changes

introduced by the Windsor Framework include removing the requirements of the EU Falsified Medicines

Directive (FMD) from products intended for Northern Ireland and a requirement that all medicines placed on the

UK market be labeled “UK Only.”

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E. Greater China

Mainland China

Similar to the United States and the European Union, Mainland China has rules governing the approval for

development and commercialization of drugs, including specialized rules for vaccines. China’s drug law and

regulations require that NMPA’s Center for Drug Evaluation, or CDE, approve a clinical trial application prior to

initiating a study to support the safety and effectiveness of a drug, including a therapeutic or preventive biologic

(i.e., a vaccine). This clinical trial application generally takes approximately 60 business days but may be

expedited to 30 business days in the case of innovative drugs that meet certain conditions.

Once approved, vaccine clinical trials must be conducted at sites that are qualified disease prevention and

control, or CDC, institutions and grade III hospitals, and the implementation of the trial must be in accordance

with China’s general drug and specialized vaccine good clinical practice regulations and related guidelines.

Other drug trials must be conducted at designated hospital sites in accordance with China’s general drug good

clinical practice rules. Furthermore, prior to the commencement of the clinical trial in China each site’s ethics

committee must approve the trial, and the National Health Commission must approve the collection and use of

certain human samples containing genetic material and related genetic data. The human genetic resources, or

HGR, approval requires a joint approval or record-filing application by the Chinese and foreign parties, setting

forth the parties that will handle data and samples, the type and amount of samples that will be utilized during

the study, the tests/analysis run, and the plans for storage or destruction, and potentially the intellectual property

sharing arrangement among the parties, among other items. If the research is exploratory (i.e., not tied to a

program designed to obtain registration in China), patentable IP arising from the use of the HGR samples and

data must be jointly owned by the Chinese and foreign parties. Once approved, the HGR approval/filing may

require updates and amendments and additional procedures to transfer data to foreign parties that are not on the

approval. A final report is due at the end of the study.

Once a clinical trial in China is complete and/or foreign data is assembled, a company may submit an application

for a marketing authorization, or MA, of the drug. This procedure will include submission of pre-clinical and

clinical data, manufacturing information and test results, among other items, and may include an onsite pre-

market verification by the Center for Food and Drug Inspections of NMPA. This application may be considered

more quickly if the applicant qualifies for admission to various expedited programs, including breakthrough

designation for drugs that are new to the world in some respect, treat life threatening or quality of life altering

diseases and either have no comparator on the market or represent a significant clinical advantage over existing

approved therapies. Conditional approval procedures permit approval of a drug based on earlier stage data, but

subject continued marketing to the fulfillment of post-market conditions with a designation period of time, such as

the completion of additional studies. Therapeutic biologics and small molecule drugs follow similar steps to

approval for development and marketing. These steps are similar for drugs that are imported and those that are

produced domestically in China. However, domestically produced drugs must be produced at a facility that also

obtains a drug manufacturing license based, in part, on a pre-marketing good manufacturing practice inspection.

At both the clinical trial and MA stages, applicants for imported drugs must list a regulatory agent on the

application. The agent must be an entity in China. An imported drug MA holder must also make a filing to a

provincial level government appointing a domestic responsible entity, which is an entity that assists the

marketing authorization holder, or MAH, with fulfilling its post-market drug regulatory obligations in China. The

domestic responsible entity of the MAH is jointly liable with the MAH for these drug regulatory obligations.

Once approved, vaccines may be procured by the CDC through platforms organized by the provincial

governments. Vaccines in China must be sold and directly distributed by domestic manufacturers or general

distributors appointed to represent overseas makers to municipal level CDCs, which handle allocation and

distribution to points of vaccination in China. Distribution of other drugs occurs through procurement processes

for sales at public hospitals or sales to private hospitals or pharmacies. Distributors of all drugs must possess a

MA for the drug they are distributing for wholesale or a drug distribution license for wholesale or retail activities.

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As is the case with all drugs, once on the market, MAHs will also have post-market obligations, including

fulfillment of post-marketing commitments that were part of the grant of their MA. In the case of vaccines, MAHs

must pay compensation for injuries caused adverse events following inoculation, or AEFIs, if the vaccine is not

one required as part of the National Inoculation Program. The government bears the cost of NIP vaccines and

related AEFIs. All drug MAHs are subject to other post-market obligations for drug marketing authorization

holders, including recalls, adverse reaction reporting, annual reporting, and inspections. All drug MAs must be

renewed every five years, and supplemental applications, notifications, or reports may need to be submitted for

major, moderate and minor changes, respectively, to the original registration (e.g., significant manufacturing

changes).

Advertisements of prescription drugs, including vaccines, must be pre-approved and may only be placed in

approved medical journals. Other forms of “academic promotion” may be performed by medical representatives

who are authorized in writing by MAHs (or their agents) and their information filed on government designated

websites. Currently, medical representatives are permitted to provide information about the drug to health care

professionals (in accordance with certain procedural rules) and collect feedback as to drug safety, although a

proposed revision to this rule may further restrict the activities of the medical representatives.

Hong Kong and Macao

Mainland China’s drug regulatory system does not apply in Hong Kong or Macao. These administrative regions

are governed by separate laws on the development, approval, manufacturing, distribution and advertising and

promotion of drugs, including vaccines. Similar rules restricting advertising and promotional content and, in the

case of Macao, government approved advertisements, also apply.

F. Türkiye

Other countries such as Türkiye and those in the Middle East have regulatory review processes and data

requirements for medicinal products, including vaccines, similar to those described for the European Union. The

regulatory licensing process in these countries may include local marketing authorization requirements,

manufacturing/testing facility inspections, testing of drug product upon importation and other domestic

requirements. Some countries, such as Türkiye, have introduced specific emergency authorization regimes for

COVID-19 vaccines.

G. Rest of the World Regulation

The requirements governing the conduct of clinical trials, product (including vaccine) licensing, pricing, and

reimbursement vary from country to country in markets outside the European Union and the United States. In

many markets, clinical trials must be conducted in accordance with Good Clinical Practice and applicable

regulatory requirements. Ethical standards typically follow the Declaration of Helsinki principles. In response to

the COVID-19 pandemic, some markets have granted or are considering the grant of emergency use

authorizations for vaccine candidates instead of the otherwise available regulatory approval pathways. Supply of

the COVID-19 vaccine to a number of countries outside of the United States and the European Union is similarly

governed by vaccine supply agreements with local governments.

In Africa, there is limited harmonization of the regulation of drug and biological products across the continent,

and the functionality and regulatory capacity of national medicines regulatory authorities varies between

jurisdictions. For example, many regulators lack the technical expertise to independently assess marketing

authorization applications and instead have adopted “reliance” procedures, whereby authorization by a foreign

stringent regulatory authority or registration as a WHO pre-qualified product may be a condition for approval. The

African Union (“AU”) has issued several harmonization initiatives for medicines, including adopting the AU Model

Law on Medical Products Regulation in 2016 and establishing the African Medicines Agency, or AMA, in 2019.

The AMA’s responsibilities will include evaluating medicines for the treatment of priority diseases, among other

harmonization-related responsibilities, but has yet to issue any regulatory guidelines or procedures to date.

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Failure to adhere to regulatory requirements may lead to, among others, fines, suspension or withdrawal of

regulatory authorizations or approvals, product recalls, seizure of products, restrictions or suspensions of

operations, or criminal prosecution.

H. Healthcare Law and Regulation

Healthcare providers and third-party payors play a primary role in the recommendation and prescription of

pharmaceutical products that are granted marketing approval. Our current and future arrangements with

providers, researchers, consultants, third-party payors and customers are subject to broadly applicable federal

and state fraud and abuse, anti-kickback, false claims, transparency and patient privacy laws and regulations

and other healthcare laws and regulations that may constrain our business and/or financial arrangements.

Restrictions under applicable federal and state healthcare laws and regulations in the United States and

elsewhere include, without limitation, the following:

–the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from

knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in-cash or in

kind, to induce or reward 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 does not need to have actual knowledge of the statute or a

specific intent to violate it in order to have committed a violation. Moreover, 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 U.S. federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary

penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or

causing to be presented, to the federal government, claims for payment that are false, fictitious, or fraudulent

or knowingly making, using, or causing to be made or used a false record or statement to avoid, decrease, or

conceal an obligation to pay money to the federal government;

–HIPAA, which created additional U.S. federal criminal laws that prohibit, among other things, knowingly and

willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making

false statements relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity

does not need to have actual knowledge of the statute or a specific intent to violate it in order to have

committed a violation;

–HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their

respective implementing regulations, including the Final Omnibus Rule published in January 2013, which

impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security

and transmission of individually identifiable health information without the appropriate authorization by entities

subject to the law, such as healthcare providers, health plans and healthcare clearinghouses and their

respective business associates;

–the U.S. federal transparency requirements, known as the federal Physician Payments Sunshine Act, under

the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report

annually to the Centers for Medicare & Medicaid Services, or CMS, within the U.S. Department of Health and

Human Services, information related to payments and other transfers of value made by that entity to

physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their

immediate family members;

–U.S. federal consumer protection and unfair competition laws, which broadly regulate marketplace activities

and activities that potentially harm consumers;

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–U.S. federal government price reporting laws, which require us to calculate and report complex pricing metrics

to government programs and which may be used in the calculation of reimbursement and/or discounts on

marketed products;

–the Foreign Corrupt Practices Act, a U.S. law which regulates certain financial relationships with foreign

government officials (which could include, for example, certain medical professionals);

–the national anti-bribery laws and laws governing interactions with healthcare professionals of European

Union member states;

–the U.K. Bribery Act 2010; and

–analogous laws and regulations in U.S. states and other jurisdictions, such as U.S. state anti-kickback and

false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental

third-party payors, including private insurers.

Some U.S. state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary

compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition

to requiring pharmaceutical manufacturers to report information related to payments to physicians and other

health care providers or marketing expenditures and pricing information. Laws in U.S. states and other

jurisdictions also govern the privacy and security of health information in some circumstances, many of which

differ from each other in significant ways and often are not preempted by HIPAA, thus complicating 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. U.S.

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.

Violations of these laws can subject us to criminal, civil and administrative sanctions including monetary

penalties, damages, fines, disgorgement, individual imprisonment and exclusion from participation in

government funded healthcare programs, such as Medicare and Medicaid, additional reporting requirements and

oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of

non-compliance with these laws, reputational harm, and we may be required to curtail or restructure our

operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business

is found to be not 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 the business. Moreover, we expect that there will continue to be federal and state laws

and regulations, proposed and implemented, that could impact our future operations and business.

I. Current and Future Healthcare Reform Legislation

In the United States and other jurisdictions, there have been a number of legislative and regulatory changes and

proposed changes regarding the healthcare system that could prevent or delay marketing approval of our

product candidates, restrict or regulate post-approval activities, and affect our ability to profitably sell any product

candidates for which we obtain marketing approval. We expect that current laws, as well as other healthcare

reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in

additional downward pressure on the price that we, or any collaborators, may receive for any approved products.

The incoming new United States presidential administration may seek to pursue different or additional

approaches to drug pricing and reimbursement or could seek additional legislation affecting drug pricing, either

of which could affect future profitability.

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Additionally, other federal health reform measures have been proposed and adopted in the United States in

recent years:

–The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several

providers, and increased the statute of limitations period for the government to recover overpayments to

providers from three to five years.

–The Middle Class Tax Relief and Job Creation Act of 2012 required that CMS reduce the Medicare clinical

laboratory fee schedule by 2% in 2013, which served as a base for 2014 and subsequent years. In addition,

effective January 1, 2014, CMS also began bundling the Medicare payments for certain laboratory tests

ordered while a patient received services in a hospital outpatient setting.

Further, there has been heightened governmental scrutiny in the United States and elsewhere over the manner

in which manufacturers set prices for their marketed products, which have resulted in several recent

Congressional inquiries and proposed bills 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 products. In addition, the U.S. federal government, state legislatures,

and other governments have shown significant interest in implementing cost containment programs, including

price-controls, restrictions on reimbursement, and requirements for substitution of generic products for branded

prescription drugs to limit the growth of government-paid health care costs. For example, the U.S. federal

government has passed legislation requiring pharmaceutical manufacturers to provide rebates and discounts to

certain entities and governmental payors to participate in federal healthcare programs. Individual states in the

United States have also become increasingly aggressive in passing legislation and implementing regulations

designed to control pharmaceutical and biological 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.

J. Packaging and Distribution in the United States and Other Jurisdictions

If our products are made available to authorized users of the Federal Supply Schedule of the General Services

Administration, additional laws and requirements apply in the United States (and similar laws may apply in other

jurisdictions). Products must meet applicable child-resistant packaging requirements under the U.S. Poison

Prevention Packaging Act. Manufacturing, sales, promotion and other activities also are potentially subject to

federal and state consumer protection and unfair competition laws.

The distribution of pharmaceutical products is subject to additional requirements and regulations, including

extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized

sale of pharmaceutical products.

The failure to comply with any of these laws or regulatory requirements subjects firms to possible legal or

regulatory action. Depending on the circumstances, failure to meet applicable regulatory requirements can result

in criminal prosecution, fines or other penalties, injunctions, exclusion from federal healthcare programs,

requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal of product

approvals, or refusal to allow a firm to enter into supply contracts, including government contracts. Any action

against us for violation of these laws, even if we successfully defend against it, could cause us to incur

significant legal expenses and divert our management’s attention from the operation of our business.

Prohibitions or restrictions on sales or withdrawal of future products marketed by us could materially affect our

business in an adverse way.

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.

If any such changes were to be imposed, they could adversely affect the operation of our business.

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K. Other Environmental, Health and Safety Laws and Regulations

In the United States, the European Union and other jurisdictions, 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 employers’ liability 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.

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.

L. Regulation of Artificial Intelligence Systems and Models

Government authorities in the United States at the federal, state and local levels have been actively engaged in

advancing policy frameworks, guidance documents, discussion papers, standards, and proposed legislation

regarding the development and use of AI by life sciences companies and, where applicable, applying existing

regulatory frameworks (e.g., FDA regulations) to particular uses of AI. Likewise, the EU and other countries and

jurisdictions extensively regulate (or intend to extensively regulate) the development and use of AI systems and

models. The processes for monitoring emerging regulatory frameworks, evaluating how current and emerging

requirements for AI apply to our business, along with subsequent compliance with applicable requirements and

best practices, require the expenditure of substantial time and financial resources.

A biotech company could use AI in a number of different contexts. For example, it may use AI in the medicines

lifecycle for drug discovery, for non-clinical research and development, for data analysis in clinical trials and

analysis of real world data, for precision medicine (e.g., clinical decision support), for supporting clinical trial

design or assessing patient eligibility for clinical trials, for drafting medicinal product information documents, in

the manufacturing of medicinal products and in machinery, or to assist with post-authorization safety monitoring,

among other potential uses. If the AI is intended to perform a regulated activity (such as related to drug

manufacturing, release testing, or producing clinical/diagnostic outputs) or otherwise be used in operations that

are the subject of scrutiny by health authorities, the use of AI could trigger health authority oversight and, in

some cases, application of existing laws and regulations relevant to healthcare, pharmaceuticals, and/or medical

devices or sector-agnostic AI laws and regulations.

Outside the drug development and commercialization context, a biotech company may use AI for other

operational reasons. For example, a company may have plans to use automated personnel recruitment tools,

deploy facial recognition technology to ensure security of its services, use customer service chatbots, or allow its

employees to use generative AI or general-purpose AI tools to increase the efficiencies of administrative tasks.

A company will need to identify how it uses AI in its business operations, and identify the relevant applicable

regulatory regime that applies to ensure compliance. Failure to adhere to (or remain up to date with evolving)

regulatory requirements may lead to compliance actions, penalties and other risks.

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United States

In the United States, Congress, the White House, various federal agencies, and states have advanced proposed

AI legislation, policy frameworks, guidance documents, whitepapers, and governing principles to address the use

of AI, including when used in healthcare and life sciences. Of particular relevance to biotech companies, the FDA

has been adapting and applying existing regulatory frameworks to account for AI and has issued guidance,

discussion papers, and frameworks outlining FDA’s approach to regulation and oversight of health-related uses

of AI. To date, FDA has not issued a new regulatory framework specific to AI; rather, it has been applying its

existing regulations for drug and biologic discovery, development, clinical testing and manufacturing to

companies utilizing AI in these processes, such that companies seeking to incorporate AI into processes that are

subject to FDA oversight need to demonstrate compliance with the existing regulations for drug and biologic

sponsors. In this context, FDA issued two discussion papers on the use of AI in drug manufacturing (March

2023) and the development of drug and biological products (May 2023), and hosted a related public workshop in

August 2024. Following feedback on the discussion papers and the workshop, in January 2025, FDA issued its

first draft guidance document regarding uses of AI in drug development and other parts of the drug lifecycle,

entitled “Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and

Biological Products.” AI to support regulatory decision-making, within the scope of the draft guidance, includes AI

intended to support regulatory determinations made by FDA (e.g., with respect to safety or effectiveness of a

drug in a New Drug Application) and to support actions taken by sponsors in conformance with FDA’s regulatory

authority (e.g., current good manufacturing practices, post-marketing requirements, and INDs). The draft

guidance proposes a seven-step risk-based framework for assessing the risk and credibility of AI models

intended to support regulatory decision-making to determine whether the AI model is adequate for a specific use,

and describes the associated documentation FDA may expect to review in an application or during an inspection.

FDA also actively regulates some health-related AI as “software as a medical device,” or SaMD, under FDA’s

existing medical device frameworks and has issued guidance describing specific regulatory considerations that

may apply to AI-based SaMD. Most recently, FDA issued draft guidance in January 2025 on lifecycle

management and marketing submission recommendations for AI-enabled device software functions, and hosted

its inaugural Digital Health Advisory Committee meeting in November 2024 to discuss total product lifecycle

considerations for generative AI-enabled devices.

Additionally, at the executive level, the Trump Administration revoked a Biden Administration Executive Order on

the Safe, Secure, and Trustworthy Development of Artificial Intelligence that Order contained a number of

directives that would have impacted the life sciences sector, including directives to HHS to establish an AI “Task

Force” responsible for issuing guidance on a number of AI topics (such as long-term safety and real-world

performance monitoring, predictive and generative AI, equity principles, and privacy and security standards),

develop a strategy for regulating the use of AI in drug development processes, develop an “AI assurance policy”

to evaluate the performance of AI-enabled healthcare tools, and establish a common framework for capturing

clinical errors resulting from AI deployed in healthcare settings. The Trump Administration issued a new

Executive Order in January 2025 on Removing Barriers to American Leadership in Artificial Intelligence that

established a policy of “global AI dominance” and directed entities to suspend, revise, or rescind any actions

taken under the Biden Administration Executive Order that are inconsistent with this policy.

Members of Congress also have introduced a number of bills on AI regulation and frameworks for regulating AI.

For example, the Bipartisan House AI Task Force released an AI report in December 2024 and the Bipartisan

Senate AI Working Group released a roadmap for AI policy in May 2024, both of which included sections on

policy recommendations for AI in health care. Senator Bill Cassidy (R-LA), who now chairs the Senate Health,

Education, Labor, and Pensions Committee, also released a whitepaper on the “Framework for the Future of AI”

in September 2023 that disfavored a “one-size-fits-all” approach to AI regulation and instead called for a flexible

approach that takes into account the context of use and leverages existing frameworks.

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U.S. state legislatures also have actively pursued AI legislation. For example, the Colorado AI Act imposes

requirements for developers and deployers of certain high-risk AI systems, and other laws will require notice or

disclosures for certain uses of generative AI or other AI systems. In addition to proposed and passed legislation,

regulators have sought to apply existing legal authorities to AI systems, including in the life sciences sector. For

example, the California Attorney General issued a legal advisory providing guidance to healthcare providers,

vendors, investors, and other healthcare entities that develop, sell, and use AI systems and similar technologies.

The advisory advised entities on their obligations under existing California law and described certain health-

related uses of AI or marketing practices that might be unlawful.

We continue to monitor developments in the regulation of AI in drug and biologic development and

commercialization, or for more general business practices, and to assess the applicability of these evolving

frameworks and policies as well as existing legal frameworks that apply to our uses of AI. If we fail to meet

regulator expectations or comply with applicable requirements, that could impact our ability to utilize AI-related

processes or information in our development of product candidates or could subject us to delays, penalties or

other risks.

European Union

The EU Artificial Intelligence Act, or the EU AI Act, entered into force on August 1, 2024. It establishes rules

governing certain AI systems and general-purpose AI models that apply across the EU. It applies to various

actors along the AI value chain, including “providers” and “deployers” of AI systems classified as “high-risk,”

“providers” of general-purpose AI models, and “providers” of general-purpose AI models with “systemic risk.” It

also prohibits certain AI practices and imposes transparency requirements in relation to certain AI systems and

general-purpose AI models.

The EU AI Act sets out a transition period of two years (by August 2026) for most provisions, with the following

exceptions: (i) the provisions relating to prohibited AI practices and AI literacy apply after six months (by

February 2025); (ii) the provisions relating to general-purpose AI models and the AI Act’s governance framework

apply after one year (by August 2025); and (iii) the provisions relating to high-risk AI systems that are used as

safety components of products or are themselves products regulated by certain EU harmonization legislation

(e.g., machinery, medical devices) requiring third-party conformity assessments apply after three years (by

August 2027).

The EU AI Act applies to providers, located in or outside the EU, that place on the market or put into service AI

systems in the EU, or that place on the market general-purpose AI models in the EU. It also applies to deployers

of AI systems located or established in the EU, and to providers or deployers located or established outside the

EU where the output of the system is used in the EU. Whether a biotech company incurs obligations under the

EU AI Act depends on whether it develops, offers, or uses any AI systems or general-purpose AI models;

whether it qualifies as a “provider,” “deployer,” or other regulated actor; and the jurisdiction where the system is

put into service, where the system or model is placed on the market, or where the output of a system is used.

Providers and deployers of “high-risk AI systems” will need to comply with numerous obligations that apply to

such systems. The obligations for providers and deployers differ, with the majority of obligations falling to

providers. The EU AI Act also contemplates circumstances where a deployer or other third-party must assume

the obligations of the provider, e.g., where the third-party makes a substantial modification to a high-risk AI

system that has already been placed on the market or put into service, but where the modified system remains

high risk. The EU AI Act sets out an exhaustive list of “high-risk AI systems” in Annexes I and III. The categories

of such systems that might be relevant to offerings of biotech companies include products that require a notified

body conformity assessment under the EU Medical Devices Regulation 2017/745 or EU In Vitro Diagnostic

Medical Devices Regulation 2017/746.

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The EU AI Act imposes a separate set of obligations on providers of “general-purpose AI models” and an

additional set of obligations on providers of “general-purpose AI models with systemic risk.” The European

Commission will designate general-purpose AI models that have “high-impact capabilities” as models with

“systemic risk.” Providers of general-purpose AI models—with or without “systemic risk”— must comply with

certain obligations, including to draw up technical documentation about the general-purpose AI model,

implement a copyright policy to comply with EU copyright laws, and make available a summary of the content

used to train the model. Additional obligations apply to providers of general-purpose AI models with systemic

risk, including, for example, to perform model evaluation (such as adversarial testing) and to report serious

incidents to the European Commission’s AI Office. Whether these obligations apply to a biotech company will

depend on whether it develops any general-purpose AI models (or have them developed on its behalf) and

places them on the market in the EU. If so, it will need to comply with the obligations that apply to all general-

purpose AI models and assess whether any of these models could qualify as general-purpose AI models with

systemic risk, which would require it to comply with additional obligations.

Of particular relevance to the biotech industry, the EMA has published a reflection paper on the use of AI

(September 2024), which is aimed at biopharmaceutical companies intending to use AI in the lifecycle of their

medicines, including for drug discovery, design, and development. It also covers the use of medical devices with

AI/machine-learning (ML) technology that are used to generate data or other evidence to support an EU

marketing authorization for a medicine (i.e., used within the context of clinical trials or combined with the use of a

medicine). The EMA’s view of “high patient risk” or “high regulatory impact” that AI can have differs from the

classifications used in the EU AI Act. This requires biotech companies to assess whether the use of AI could

affect patient safety (“high patient risk”) or impact regulatory decision-making (“high regulatory impact”) for the

purpose of the EU medicines rules. This means that potentially, non-high-risk AI under the EU AI Act could still

be relevant to the EMA if it impacts patient safety or evidence generation for a medicine subject to regulatory

approval. The EMA guidance puts the onus on marketing authorization applicants/marketing authorization

holders to ensure AI used during the medicines lifecycle is compliant with the medicines rules. If a biotech

company intends to use AI in the context of its medicines it will need to carry out a regulatory impact and risk

analysis and potentially discuss use cases with the EMA, including when there is no clearly written guidance

available.

Failure to adhere to (or remain up to date with evolving) EU regulatory requirements may lead to delays,

compliance risks, and penalties.

Rest of World

Outside the United States and EU, the requirements governing the use and deployment of AI may vary from

country to country, though health regulators have taken some steps toward international harmonization on AI

best practices. For example, FDA, UK MHRA, and Health Canada have issued joint guiding principles on topics

such as good machine learning practices and transparency for ML-enabled devices. A company will need to

identify how it uses AI in its business operations, and identify the relevant applicable regulatory regime that

applies to ensure compliance. Failure to adhere to (or remain up to date with evolving) regulatory requirements

may lead to delays, compliance risks, and penalties.

X. Intellectual Property

A. Introduction

We pursue a layered intellectual property strategy to protect our various technology platforms and their

application to the treatment of serious diseases, such as cancer and infectious diseases including COVID-19.

One focus of our intellectual property strategy is to provide protection for our platforms and products as they are

developed. We also pursue intellectual property protection for assets that may be used in future development

programs, may be of interest to our collaborators, and/or otherwise may prove valuable in the field.

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Various aspects of our technology platforms and our product candidates are claimed in patent filings. We also

pursue other modalities of intellectual property protection, including trademark and trade secret protection, as

appropriate. Many of our intellectual property assets were developed and are owned solely by us, some have

been developed via collaboration and are jointly owned, and some have been acquired by acquisition and/or

licensed from third parties. We expect that we will continue to make additional patent application filings, and will

continue to pursue opportunities to acquire and license additional intellectual property assets, technologies,

platforms and/or product candidates, as developments arise or are identified.

Regardless, we cannot be certain that any of the patent filings or other intellectual property rights that we have

pursued or obtained will provide protection for any products as commercialized. As further variants of SARS-

CoV-2 arise, and its impact and characteristics evolve, the composition, manufacture, and use (including, e.g.,

dosage regimen) of our COVID-19 vaccine products may be adjusted or modified and our filings may not protect

them.

Our future commercial success depends, in part, on our ability to obtain and maintain patent and other

proprietary protection for commercially important technology, inventions and know-how related to our business;

defend and enforce our patents and other intellectual property; preserve the confidentiality of our trade secrets;

and operate without infringing, misappropriating or violating the valid and enforceable patents and other

intellectual property rights of third parties. Our ability to stop 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 rights that cover these activities. With respect to both our

owned and licensed intellectual property, we cannot be sure that patents will issue with respect to any of the

owned or licensed pending patent applications or with respect to any patent applications that we, our co-owners

or our licensors may file in the future, nor can we be sure that any of our owned or licensed patents or any

patents that may be issued in the future to us or our licensors will be commercially useful in protecting any

products that we ultimately attempt to commercialize or any method of making or using such products. Moreover,

we may be unable to obtain patent protection for certain of our product candidates generally as well as with

respect to certain indications. See “Risk Factors—Risks Related to Intellectual Property” in this Annual Report.

As of January 1, 2026, our overall owned and in-licensed patent portfolio included more than 600 patent families,

each of which includes, or can in the future include, at least one filing in the United States or Europe, and several

of which are pending or granted in multiple jurisdictions. The patent families include at least 560 patent families

that are solely or jointly owned by BioNTech, including certain families acquired through our acquisitions and

others that we have licensed from a third party.

An issued patent provides its owner (or possibly its licensee) with a right to exclude others from making, using or

selling that which is claimed in the patent, for a specified period of time (the “term” of the patent), in the

jurisdiction in which the patent is issued. In the United States, and in many other countries, patents have a

presumptive term of 20 years from their effective filing date (which is the earliest non-provisional filing date to

which the patent claims priority). However, many jurisdictions, including the United States, require the payment

of periodic maintenance fees in order for patents to remain in force for the full 20-year term. The United States

also has provisions that require a patent term to be shortened if its claims are too similar to another patent

owned by the same party that has a shorter term. The United States and certain other jurisdictions also have

provisions that permit extension of patent term for patents that claim a drug or drug product, or its approved use,

if the patent was issued before clinical trials were completed and certain other requirements were satisfied. In

the United States, such extension is called a Patent Term Extension, or PTE, and it is limited to a period of not

more than five years, or the total patent term including the PTE cannot exceed 14 years after the date of

regulatory approval; only one patent can be extended per product approval. We did not extend any patent for our

COVID-19 vaccine (Comirnaty) when it was approved by the FDA in the United States in 2021. The United

States also offers a different form of patent term extension, known as Patent Term Adjustment, or PTA, whereby

a particular patent’s term is automatically extended beyond the 20-year date if the U.S. Patent and Trademark


		Page

GENERAL INFORMATION		4
CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS		5

PART I

ITEM 1.	IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS	8

ITEM 2.	OFFER STATISTICS AND EXPECTED TIMETABLE	8

ITEM 3.	KEY INFORMATION	8
	A. [Reserved]	8
	B. Capitalization and Indebtedness	8
	C. Reasons for the Offer and Use of Proceeds	8
	D. Risk Factors	8

ITEM 4.	INFORMATION ON THE COMPANY	104
	A. History and Development of the Company	104
	B. Business Overview	104
	C. Organizational Structure	180
	D. Property, Plant and Equipment	181

ITEM 4A.	UNRESOLVED STAFF COMMENTS	181

ITEM 5.	OPERATING AND FINANCIAL REVIEW AND PROSPECTS	182
	A. Operating Results	182
	B. Liquidity and Capital Resources	189
	C. Research and Development, Patents and Licenses, etc.	193
	D. Trend Information	193
	E. Critical Accounting Estimates	193
	F. Comparison of the year ended December 31, 2024 and the year ended December 31, 2023	193

ITEM 6.	DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES	193
	A. Directors and Senior Management	193
	B. Compensation	198
	C. Board Practices	211
	D. Employees	218
	E. Share Ownership	218
	F. Disclosure of a Registrant’s Action to Recover Erroneously Awarded Compensation	219

ITEM 7.	MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS	219
	A. Major Shareholders	219
	B. Related Party Transactions	220
	C. Interests of Experts and Counsel	221


ITEM 8.	FINANCIAL INFORMATION	221
	A. Consolidated Statements and Other Financial Information	221
	B. Significant Changes	221

ITEM 9.	THE OFFER AND LISTING	221
	A. Offer and Listing Details	221
	B. Plan of Distribution	221
	C. Markets	221
	D. Selling Shareholders	221
	E. Dilution	221
	F. Expenses of the Issue	221

ITEM 10.	ADDITIONAL INFORMATION	221
	A. Share Capital	221
	B. Memorandum and Articles of Association	221
	C. Material Contracts	227
	D. Exchange Controls	227
	E. Taxation	228
	F. Dividends and Paying Agents	239
	G. Statement by Experts	239
	H. Documents on Display	239
	I. Subsidiary Information	240
	J. Annual Report to Security Holders	240

ITEM 11.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	240

ITEM 12.	DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES	241
	A. Debt Securities	241
	B. Warrants and Rights	241
	C. Other Securities	241
	D. American Depositary Shares	242

PART II

ITEM 13.	DEFAULTS, DIVIDEND ARREARAGES AND DELINQUENCIES	244

ITEM 14.	MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS	244

ITEM 15.	CONTROLS AND PROCEDURES	244

ITEM 16.	[RESERVED]	245

ITEM 16A.	Audit Committee Financial Expert	245

ITEM 16B.	Code of Ethics	245

ITEM 16C.	Principal Accountant Fees and Services	245

ITEM 16D.	Exemptions from the Listing Standards for Audit Committees	246

ITEM 16E.	Purchases of Equity Securities by the Issuer and Affiliated Purchasers	246

ITEM 16F.	Changes in Registrant’s Certifying Accountant	246



ITEM 16G.	Corporate Governance	247

ITEM 16H.	Mine Safety Disclosure	254

ITEM 16I.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	254

ITEM 16J.	Insider Trading Policies	254

ITEM 16K.	Cybersecurity	254

PART III

ITEM 17.	FINANCIAL STATEMENTS	257

ITEM 18.	FINANCIAL STATEMENTS	257

ITEM 19.	EXHIBITS	257