S-1/A 1 d579945ds1a.htm AMENDMENT NO 4 TO FORM S-1 Amendment No 4 to Form S-1
Table of Contents

As filed with the Securities and Exchange Commission on September 19, 2013

Registration No. 333-190566

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

Amendment No. 4

to

FORM S-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

 

 

BIND Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   2834   56-2596148

(State or other jurisdiction of

incorporation or organization)

 

(Primary Standard Industrial

Classification Code Number)

 

(I.R.S. Employer

Identification No.)

325 Vassar Street

Cambridge, Massachusetts 02139

(617) 491-3400

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

 

 

Scott Minick

President and Chief Executive Officer

BIND Therapeutics, Inc.

325 Vassar Street

Cambridge, Massachusetts 02139

(617) 491-3400

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

 

 

Copies to:

 

Peter N. Handrinos

B. Shayne Kennedy

Matthew T. Bush

Latham & Watkins LLP

John Hancock Tower, 20th Floor

200 Clarendon Street

Boston, Massachusetts 02116

(617) 948-6000

 

Bruce K. Dallas

Davis Polk & Wardwell LLP

1600 El Camino Real

Menlo Park, California 94025

(650) 752-2000

 

 

Approximate date of commencement of proposed sale to the public:

As soon as practicable after this Registration Statement is declared effective.

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

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

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

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

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

 

Large accelerated filer  ¨    Accelerated filer  ¨    Non-accelerated filer  x    Smaller reporting company  ¨
     

(Do not check if a

smaller reporting company)

  

 

 

CALCULATION OF REGISTRATION FEE

 

 

Title of Each Class of

Securities To Be Registered

 

Amount

to be
Registered(1)

  Proposed
Maximum
Offering Price
Per Share(2)
 

Proposed

Maximum Aggregate

Offering Price(2)

 

Amount of

Registration Fee(3)(4)

Common Stock, $0.0001 par value per share

  5,405,000   $16.00   $86,480,000   $11,795.88

 

 

(1) Includes 705,000 shares that the underwriters have the option to purchase.
(2) Estimated solely for the purpose of calculating the registration fee pursuant to Rule 457(a) under the Securities Act of 1933, as amended.
(3) Calculated pursuant to Rule 457(a) based on an estimate of the proposed maximum aggregate offering price.
(4) Previously paid.

 

 

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

 

 

 


Table of Contents

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

 

SUBJECT TO COMPLETION DATED SEPTEMBER 19, 2013

PRELIMINARY PROSPECTUS

4,700,000 Shares

 

LOGO

Common Stock

 

 

This is the initial public offering of our common stock. Prior to this offering, there has been no public market for our common stock. The initial public offering price of our common stock is expected to be between $14.00 and $16.00 per share.

Our common stock has been approved for listing on the NASDAQ Global Select Market under the symbol “BIND.”

The underwriters have an option to purchase a maximum of 705,000 additional shares of common stock from us.

We are an emerging growth company as that term is used in the Jumpstart Our Business Startups Act of 2012 and, as such, have elected to comply with certain reduced public company reporting requirements for this prospectus and future filings.

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

 

     Price to Public      Underwriting
Discounts and
Commissions(1)
     Proceeds to
BIND Therapeutics
 

Per Share

     $                         $                         $                   

Total

     $                         $                         $                   

 

(1) See “Underwriting” beginning on page 153 for additional information regarding underwriting compensation.

 

 

Certain affiliates of our directors and other principal stockholders have indicated an interest in purchasing an aggregate of approximately $14.7 million in shares of our common stock in this offering at the initial public offering price. However, because indications of interest are not binding agreements or commitments to purchase, the underwriters may determine to sell more, less or no shares in this offering to any of these stockholders, or any of these stockholders may determine to purchase more, less or no shares in this offering.

Delivery of the shares of common stock will be made on or about                , 2013.

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

 

Credit Suisse   Cowen and Company
Stifel   JMP Securities

The date of this prospectus is                , 2013


Table of Contents

TABLE OF CONTENTS

 

     Page  

PROSPECTUS SUMMARY

     1   

RISK FACTORS

     11   

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

     45   

USE OF PROCEEDS

     46   

DIVIDEND POLICY

     46   

CAPITALIZATION

     47   

DILUTION

     49   

SELECTED CONSOLIDATED FINANCIAL
DATA

     52   

MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

     54   

BUSINESS

     77   

MANAGEMENT

     112   

EXECUTIVE AND DIRECTOR
COMPENSATION

     119   

CERTAIN RELATIONSHIPS AND RELATED PERSON TRANSACTIONS

     133   

PRINCIPAL STOCKHOLDERS

     137   

DESCRIPTION OF CAPITAL STOCK

     141   

SHARES ELIGIBLE FOR FUTURE SALE

     146   

MATERIAL U.S. FEDERAL INCOME TAX CONSEQUENCES TO NON-U.S. HOLDERS

     149   

UNDERWRITING

     153   

NOTICE TO CANADIAN RESIDENTS

     158   

LEGAL MATTERS

     160   

EXPERTS

     160   

WHERE YOU CAN FIND MORE INFORMATION

     160   

INDEX TO CONSOLIDATED FINANCIAL STATEMENTS

     F-1   

 

 

We have not, and the underwriters have not, authorized anyone to provide any information or to make any representations other than those contained in this prospectus or in any free writing prospectuses prepared by or on behalf of us or to which we have referred you. We take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you. This prospectus is an offer to sell only the shares offered hereby, but only under circumstances and in jurisdictions where it is lawful to do so. The information contained in this prospectus or in any applicable free writing prospectus is current only as of its date, regardless of its time of delivery or any sale of shares of our common stock. Our business, financial condition, results of operations and prospects may have changed since that date.

Through and including                , 2013 (25 days after the commencement of this offering), all dealers that buy, sell or trade shares of our common stock, whether or not participating in this offering, may be required to deliver a prospectus. This delivery requirement is in addition to the obligation of dealers to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions.

For investors outside the United States: We have not, and the underwriters have not, done anything that would permit this offering or possession or distribution of this prospectus in any jurisdiction where action for that purpose is required, other than in the United States. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of the shares of common stock and the distribution of this prospectus outside the United States.


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PROSPECTUS SUMMARY

This summary highlights information contained elsewhere in this prospectus. This summary does not contain all of the information you should consider before investing in our common stock. You should read this entire prospectus carefully, especially the “Risk Factors” section beginning on page 11 and our consolidated financial statements and the related notes appearing at the end of this prospectus, before making an investment decision.

As used in this prospectus, unless the context otherwise requires, references to “we,” “us,” “our” and “BIND” refer to the consolidated operations of BIND Therapeutics, Inc. and its consolidated subsidiaries.

Overview

We are a clinical-stage nanomedicine platform company developing Accurins, our novel targeted and programmable therapeutics. Accurins are designed with specified physical and chemical characteristics to target specific cells or tissues and concentrate a therapeutic payload at the site of disease to enhance efficacy while minimizing adverse effects on healthy tissues. Our strategy is to leverage our medicinal nanoengineering platform to develop our own pipeline of Accurins, initially in oncology, as well as Accurins in collaboration with biopharmaceutical companies. Our lead drug candidate, BIND-014, is in Phase 2 clinical trials for non-small cell lung cancer, or NSCLC, and metastatic castrate-resistant prostate cancer, or mCRPC. To date in 2013, we have announced collaborations with Amgen, Pfizer and AstraZeneca to develop Accurins based on therapeutic payloads from their product pipelines, with the potential to achieve a total of over $1 billion in upfront and future milestone payments, including over $450 million in pre-commercial milestones.

Our management team has extensive experience in the development, regulatory approval and commercialization of nanotechnology drugs. Currently, the two leading nanotechnology cancer drugs are Doxil, a liposomal doxorubicin, and Abraxane, an albumin nanoparticle paclitaxel. Our chief executive officer was the president and chief operating officer of SEQUUS Pharmaceuticals, Inc., the company that developed and commercialized Doxil. Both our chief medical officer and our head of regulatory affairs served in those roles at Abraxis Bioscience, Inc., the company that developed Abraxane. Our platform originated from the pioneering nanotechnology research at the Massachusetts Institute of Technology and Brigham and Women’s Hospital/Harvard Medical School of our scientific founders and directors Dr. Robert Langer and Dr. Omid Farokhzad. Our scientists and engineers continue to advance this technology to produce the next generation of targeted nanomedicines.

The challenge for all drugs is to maximize the net clinical benefit by increasing the desired therapeutic effect and reducing adverse effects. This is especially difficult in cancer, where the goal is to destroy or inhibit growth of cancer cells without damaging similar healthy cells. The first generation of cancer drugs were cytotoxic chemotherapies, such as Taxotere, which achieved limited selectivity by targeting mechanisms responsible for cell proliferation, a key characteristic of cancer cells. The mechanisms responsible for cell proliferation are also a property of healthy cells, which can lead to significant adverse effects when healthy cells are destroyed. Biopharmaceutical companies have developed more selective drugs, which we refer to as targeted therapies, such as Herceptin and Gleevec by targeting proteins found at higher levels on the surface of cancer cells or by inhibiting dysregulated biochemical pathways inside cancer cells. More recently, drugs such as Kadcyla have increased efficacy by linking toxins and antibodies to deliver targeted cytotoxicity. While these newer drugs were an improvement in targeting cancer cells relative to normal tissue, there continues to be a need to develop drugs with increased net clinical benefit.

We believe Accurins represent the next stage in the evolution of cancer therapy. Accurins are nanoparticles containing a therapeutic payload and are designed to target tumors at three levels: tissue, cellular and molecular. They combine this triple targeting with a prolonged circulation time to concentrate the therapeutic payload at the targeted disease site, where it is then released in a controlled and timely manner. Accurins have the potential to significantly increase the net clinical benefit of the therapeutic payload and result in efficacy and safety not currently achievable through other therapeutic approaches.

 

 

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Our lead Accurin drug candidate, BIND-014, is a prostate-specific membrane antigen, or PSMA, targeted Accurin that contains docetaxel. PSMA is a clinically-validated tumor marker expressed on prostate cancer cells and the blood vessels of many types of non-prostate solid tumors, including NSCLC. Docetaxel, marketed as Taxotere, is one of the most commonly used cancer chemotherapy drugs. It is approved by the U.S. Food and Drug Administration, or FDA, for the treatment of breast cancer, NSCLC, mCRPC, head and neck cancer, and gastric cancer. Taxotere achieved global sales of approximately $3 billion in 2009, the year prior to its loss of marketing exclusivity in the United States, and generic docetaxel continues to be a mainstay in cancer treatment despite its significant side effects. These side effects include neutropenia, anemia, infection, fluid retention and edema, neuropathy, rash, mucositis, fatigue, muscle weakness, nail loss, hair loss and even death.

We are in Phase 2 clinical trials to evaluate the level of clinical activity of BIND-014 in NSCLC and mCRPC and expect to report data from these studies in the second half of 2014. To date, we have clinically tested BIND-014 in over 45 patients with advanced or metastatic cancer who failed prior therapies. In our Phase 1 clinical trial, of the 28 patients who received BIND-014 once every three weeks, there have been one complete response in a patient with cervical cancer and three partial responses in patients with NSCLC, mCRPC and ampullary cancer. A complete response generally refers to the disappearance of all signs of cancer in response to treatment, while a partial response generally refers to a decrease in the size of the tumor or in the extent of cancer in the body. Five additional patients had stable disease lasting longer than 12 weeks. In our preclinical studies, BIND-014 has demonstrated that its ability to destroy tumor cells is differentiated from, and superior to, Taxotere.

In addition to our internal development programs, we also consider opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. Our collaborations with industry leaders, including announced agreements with Amgen, Pfizer and AstraZeneca, provide us with the opportunity to develop Accurins with a broader range of therapeutic payloads than we could on our own. Our collaboration agreements generally require the collaborator to pay all the development costs associated with the Accurin, including those incurred by us. In addition, the upfront and potential milestone payments under these agreements provide us with additional capital resources to develop our own proprietary pipeline of Accurins. We expect that at least one of our collaborations will advance an Accurin into the clinic by the end of 2014.

Accurins

We believe Accurins represent the next stage in the evolution of targeted therapies and nanomedicine.

 

LOGO

 

 

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Accurins are polymeric nanoparticles that incorporate a therapeutic payload and are designed to have prolonged circulation within the bloodstream, enable targeting of the diseased tissue or cells, and provide for the controlled and timely release of the therapeutic payload. To achieve this, they have four key components:

 

   

Targeting ligands—To facilitate targeting, Accurins utilize targeting ligands on the surface of the Accurin that bind to specific cell-surface or tissue markers. Targeting ligands may include small molecules, peptides, antibodies and antibody fragments.

 

   

Stealth and protective layer—Using polyethylene glycol, or PEG, this layer is engineered to protect the Accurin from the body’s immune detection and clearance mechanisms.

 

   

Controlled-release polymer matrix—The polymer matrix entraps the therapeutic payload and mediates its release at the disease site and is engineered, or programmed, to control the release of the therapeutic payload at a predetermined rate.

 

   

Therapeutic payload—Our Accurins are designed to utilize a broad range of therapeutic payloads, including small molecules, peptides, proteins and nucleic acids, such as siRNA and mRNA.

In addition, the PEG and polymers used in our Accurins have been used in other medical products that have been approved by the FDA and other regulatory agencies.

Product Pipeline and Platform

We intend to use our medicinal nanoengineering platform to develop Accurins in several therapeutic areas, with an initial focus on the treatment of various types of cancer. In addition, we have entered into collaboration agreements with several major biopharmaceutical companies to develop and commercialize Accurins that are based on our collaborators’ proprietary therapeutic payloads. The following table depicts our proprietary and collaboration products in development:

 

LOGO

 

 

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Our Strategy

Our goal is to become a leading biopharmaceutical company developing and commercializing targeted nanomedicines to address significant unmet medical needs, with an initial focus on treatments for cancer. The critical components of our business strategy include:

 

   

Develop our lead drug candidate, BIND-014, initially in NSCLC and mCRPC. BIND-014 is in two Phase 2 trials for the treatment of second-line docetaxel-naïve NSCLC and first-line chemotherapy-naïve mCRPC. These trials are single-arm, open label studies designed to evaluate efficacy and safety in these specific tumor types so that we can move into pivotal Phase 3 trials where we will seek to establish the superiority of BIND-014 versus docetaxel. Based on initial discussions with the FDA, we expect to use the 505(b)(2) FDA approval pathway and conduct a single Phase 3 trial for each indication using similar criteria for approval as docetaxel. The 505(b)(2) approval pathway would enable us to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of docetaxel when we submit our new drug application, or NDA, to the FDA. We will also evaluate the development of BIND-014 in other oncology indications, including breast cancer, and in combination with other cancer therapies.

 

   

Develop and commercialize Accurins in collaboration with leading biopharmaceutical companies. In addition to our internal development programs, we also consider opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. We have established a number of collaborations with industry leaders, including announced agreements with Amgen, Pfizer and AstraZeneca.

 

   

Leverage our medicinal nanoengineering platform to develop a pipeline of high value Accurins. The modularity of our technology allows us to efficiently expand our pipeline of Accurins, both on our own and in collaboration with others, through various combinations of targeting ligands and therapeutic payloads, and also enables us to move into therapeutic areas beyond oncology, such as inflammatory and cardiovascular diseases.

 

   

Capitalize on drug candidates with established drug development history to accelerate development and regulatory pathway. Where possible we seek to reduce the risk, cost and time associated with drug development by capitalizing on the known efficacy, safety and established drug development history of therapeutic payloads that have already been approved and others with promising attributes that have been deemed unsuitable for further development in their untargeted form. We seek to develop Accurins that could be eligible for accelerated regulatory pathways, such as 505(b)(2), fast track designation, accelerated approval, priority review and breakthrough product designation.

 

   

Commercialize proprietary Accurins, including BIND-014, directly in the United States and with collaborators outside the United States. We have retained the worldwide rights to BIND-014 and expect to initially maintain similar rights with respect to other proprietary Accurins we develop. We intend to build a focused oncology sales organization to market FDA-approved Accurins in the United States. Outside the United States, we expect to rely on collaborators to commercialize proprietary approved Accurins.

 

   

Continue to extend and protect our product technology and Accurins through our intellectual property portfolio. We seek to protect our medicinal engineering platform through 15 issued U.S. patents and 50 U.S. patent applications that we own or license, in some cases with foreign counterparts relating to elements of our Accurin candidates, as well as know-how and trade secrets relating to the design and manufacturing of our Accurins. We expect to file additional patent applications as we apply our technology to new targets and therapeutic payloads. In addition, we believe the heightened regulatory requirements for generic nanomedicines strengthen the protection afforded by our intellectual property portfolio.

 

 

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Risks Associated with Our Business

Our business is subject to numerous risks and uncertainties, including those highlighted in the section entitled “Risk Factors” immediately following this prospectus summary. These risks include, but are not limited to, the following:

 

   

We have incurred significant losses since our inception. Our accumulated deficit was $89.3 million as of June 30, 2013, representing our cumulative losses since our inception in 2006. We expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

 

   

We will need additional funding. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

 

   

We may not be successful in our efforts to use and expand our medicinal nanoengineering platform to build a pipeline of drug candidates and develop marketable drugs.

 

   

We are very early in our development efforts and have only one drug candidate in clinical development. All of our other drug candidates are still in preclinical development. If we or our collaborators are unable to successfully develop and commercialize our drug candidates or experience significant delays in doing so, our business will be materially harmed.

 

   

Clinical drug development involves a lengthy and expensive process, with an uncertain outcome, and the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results.

 

   

Our existing collaborations are important to our business, and future collaborations may also be important to us. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could be adversely affected.

 

   

If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our drug candidates or will not be able to do so as soon as anticipated, and our ability to generate revenue will be materially impaired.

 

   

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

 

   

We face substantial competition, which may result in others discovering, developing or commercializing competing products before or more successfully than we do.

Our Corporate Information

We were incorporated under the laws of the state of Delaware in 2006 under the name BIND Biosciences, Inc., and changed our name to BIND Therapeutics, Inc. in 2013. Our principal executive offices are located at 325 Vassar Street, Cambridge, Massachusetts 02139 and our telephone number is (617) 491-3400. Our website address is www.bindtherapeutics.com. The information contained in, or accessible through, our website does not constitute a part of this prospectus.

 

 

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Implications of Being an Emerging Growth Company

As a company with less than $1.0 billion in revenue during our last fiscal year, we qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act, or JOBS Act, enacted in April 2012. An “emerging growth company” may take advantage of reduced reporting requirements that are otherwise applicable to public companies. These provisions include, but are not limited to:

 

   

being permitted to present only two years of audited financial statements and only two years of related Management’s Discussion and Analysis of Financial Condition and Results of Operations in this prospectus;

 

   

not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended;

 

   

reduced disclosure obligations regarding executive compensation in our periodic reports, proxy statements and registration statements; and

 

   

exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved.

We may use these provisions until the last day of our fiscal year following the fifth anniversary of the completion of this offering. However, if certain events occur prior to the end of such five-year period, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.0 billion or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to the end of such five-year period.

We have elected to take advantage of certain of the reduced disclosure obligations in the registration statement of which this prospectus is a part and may elect to take advantage of other reduced reporting requirements in future filings. As a result, the information that we provide to our stockholders may be different than you might receive from other public reporting companies in which you hold equity interests.

The JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.

 

 

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The Offering

 

Common stock offered by us

4,700,000 shares

 

Common stock to be outstanding after this offering

15,777,322 shares

 

Option to purchase additional shares

The underwriters have a 30-day option to purchase a maximum of 705,000 additional shares of common stock.

 

Use of proceeds

We intend to use the net proceeds from this offering to fund development of BIND-014, and for working capital and general corporate purposes. See “Use of Proceeds” beginning on page 46.

 

Risk factors

See “Risk Factors” beginning on page 11 and the other information included in this prospectus for a discussion of factors you should consider carefully before deciding to invest in our common stock.

 

NASDAQ Global Select Market symbol

“BIND”

 

 

The number of shares of our common stock to be outstanding after this offering is based on 2,339,237 shares of our common stock outstanding as of June 30, 2013, 222,646 shares of our common stock issued in August 2013 upon the automatic conversion of our Series BRN preferred stock outstanding as of June 30, 2013 and 8,515,439 shares of our common stock issuable upon the automatic conversion of all outstanding shares of our preferred stock immediately prior to the closing of this offering, and excludes:

 

   

95,419 shares of our common stock that were issued upon the automatic conversion in August 2013 of 250,000 shares of our Series BRN preferred stock issued in July 2013;

 

   

2,375,882 shares of our common stock issuable upon exercise of stock options outstanding as of June 30, 2013, at a weighted-average exercise price of $2.57 per share;

 

   

1,335,877 shares of our common stock reserved for future issuance under our 2013 Incentive Award Plan, which will become effective on the day prior to the public trading date of our common stock; and

 

   

74,413 shares of our common stock issuable upon exercise of warrants outstanding as of June 30, 2013, at a weighted-average exercise price of $11.32 per share.

Unless otherwise indicated, this prospectus reflects and assumes the following:

 

   

a 1-for-2.62 reverse stock split of our common stock effected on September 5, 2013;

 

   

the automatic conversion of 583,333 shares of our Series BRN preferred stock outstanding as of June 30, 2013 into 222,646 shares of our common stock, which occurred in August 2013 upon the initial filing of the registration statement of which this prospectus is a part, and the exclusion of the 250,000 shares of our Series BRN preferred stock issued in July 2013, which shares were automatically converted into 95,419 shares of our common stock in August 2013;

 

   

the automatic conversion of all outstanding shares of our preferred stock into 8,515,439 shares of our common stock, which will occur immediately prior to the closing of this offering;

 

   

no exercise of outstanding options or warrants after June 30, 2013;

 

 

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the filing of our restated certificate of incorporation and the adoption of our amended and restated bylaws, which will occur upon the closing of this offering; and

 

   

no exercise by the underwriters of their option to purchase additional shares of our common stock.

Certain affiliates of our directors and other principal stockholders, including entities affiliated with Polaris Venture Partners V, L.P., Flagship Ventures Fund 2004, L.P., RUSNANO, DHK Investments, LLC, ARCH Venture Fund VII, L.P. and NanoDimension, L.P., each of which is a current stockholder, have indicated an interest in purchasing an aggregate of approximately $14.7 million in shares of our common stock in this offering at the initial public offering price. However, because indications of interest are not binding agreements or commitments to purchase, the underwriters may determine to sell more, less or no shares in this offering to any of these stockholders, or any of these stockholders may determine to purchase more, less or no shares in this offering.

 

 

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Summary Consolidated Financial Data

The following tables set forth, for the periods and as of the dates indicated, our summary consolidated financial data. The consolidated statements of operations data for the years ended December 31, 2011 and 2012 are derived from our audited consolidated financial statements included elsewhere in this prospectus. The consolidated statements of operations data for the six months ended June 30, 2012 and 2013 and the consolidated balance sheet data as of June 30, 2013 are derived from our unaudited consolidated financial statements included elsewhere in this prospectus. The unaudited consolidated financial statements include, in the opinion of management, all adjustments consisting of only normal recurring adjustments, that management considers necessary for the fair presentation of the financial information set forth in those statements. You should read the following information together with the more detailed information contained in “Selected Consolidated Financial Data,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the related notes included elsewhere in this prospectus. Our historical results are not indicative of the results to be expected in the future and results of interim periods are not necessarily indicative of results for the entire year.

 

    Years Ended December 31,     Six Months Ended
June 30,
 
    2011     2012     2012     2013  
    (in thousands, except share and per share data)  

Consolidated Statements of Operations:

       

Revenue

  $ 905      $ 1,047      $ 434      $ 4,265   
 

 

 

   

 

 

   

 

 

   

 

 

 

Operating expenses:

       

Research and development

    11,440        13,052        6,228        11,617   

General and administrative

    4,787        6,625        2,830        4,416   
 

 

 

   

 

 

   

 

 

   

 

 

 

Total operating expenses

    16,227        19,677        9,058        16,033   
 

 

 

   

 

 

   

 

 

   

 

 

 

Loss from operations

    (15,322     (18,630     (8,624     (11,768

Other income (expense):

       

Interest income

    37        69        15        88   

Interest expense

    (1,708     (710     (396     (590

Change in fair value of preferred stock warrant liability

    (269     340        13        (85

Foreign currency transaction gain (loss)

    407        (309     56        147   
 

 

 

   

 

 

   

 

 

   

 

 

 

Net loss

    (16,855     (19,240     (8,936     (12,208

Accretion of redeemable convertible preferred stock

    (2,967     (4,967     (2,485     (2,749
 

 

 

   

 

 

   

 

 

   

 

 

 

Net loss attributable to common stockholders

  $ (19,822   $ (24,207   $ (11,421   $ (14,957
 

 

 

   

 

 

   

 

 

   

 

 

 

Net loss per share attributable to common stockholders:

       

Basic and diluted(1)

  $ (10.50   $ (11.70   $ (5.63   $ (6.83

Weighted average common shares outstanding:

       

Basic and diluted(1)

    1,887,082        2,069,071        2,027,221        2,190,479   

Pro forma net loss per share attributable to common stockholders (unaudited):

       

Basic and diluted(1)

    $ (1.98     $ (1.12

Pro forma weighted average common shares outstanding (unaudited):

       

Basic and diluted(1)

      9,700,591          10,928,564   

 

(1) See Note 2 to our notes to consolidated financial statements included elsewhere in this prospectus for an explanation of the method used to calculate the historical and pro forma basic and diluted net loss per common share and the number of shares used in the computation of the per share amounts.

 

 

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     As of June 30, 2013  
     Actual     Pro
Forma(1)
    Pro Forma
As
Adjusted(2)
 
    

(in thousands)

 

Consolidated Balance Sheet Data:

      

Cash and cash equivalents

   $ 21,309      $ 21,309      $ 83,999   

Working capital

     11,818        11,818        74,253   

Total assets

     31,377        31,377        92,720   

Long-term debt

     4,208        4,208        4,208   

Preferred stock warrant liability

     657        —          —     

Redeemable convertible preferred stock

     99,317        —          —     

Additional paid in capital

     —          73,249        135,684   

Accumulated deficit

     (89,286     (62,562     (62,562

Total stockholders’ (deficit) equity

     (90,342     9,632        72,067   

 

(1) The pro forma consolidated balance sheet data give effect to (a) the automatic conversion of 583,333 shares of our Series BRN preferred stock into 222,646 shares of our common stock, which occurred in August 2013 upon the initial filing of the registration statement of which this prospectus is a part, (b) the automatic conversion of all outstanding shares of our preferred stock into an aggregate of 8,515,439 shares of common stock, which will occur immediately prior to the closing of this offering, and (c) the reclassification of our preferred stock warrant liability to additional paid in capital, a component of stockholders’ (deficit) equity.
(2) The pro forma as adjusted consolidated balance sheet data give further effect to our issuance and sale of 4,700,000 shares of common stock in this offering at an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us.

Each $1.00 increase (decrease) in the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the pro forma as adjusted amount of each of cash and cash equivalents, working capital, total assets, additional paid in capital and total stockholders’ equity by approximately $4.4 million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us. Similarly, each increase (decrease) of 1.0 million shares in the number of shares offered by us at the assumed initial public offering price would increase (decrease) each of cash and cash equivalents, working capital, total assets, additional paid in capital and total stockholders’ equity by approximately $14.0 million. The pro forma information discussed above is illustrative only and will be adjusted based on the actual initial public offering price and other terms of our initial public offering determined at pricing.

 

 

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RISK FACTORS

Investing in our common stock involves a high degree of risk. You should carefully consider the risks described below, as well as the other information in this prospectus, including our financial statements and the related notes and “Management’s Discussion and Analysis of Results of Operations and Financial Condition,” before deciding whether to invest in our common stock. The occurrence of any of the events or developments described below could harm our business, financial condition, results of operations and growth prospects. In such an event, the market price of our common stock could decline, and you may lose all or part of your investment. Additional risks and uncertainties not presently known to us or that we currently deem immaterial also may impair our business operations.

Risks Related to Our Financial Position and Need for Additional Capital

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

Since inception, we have incurred significant operating losses. Our net loss was $16.9 million for the year ended December 31, 2011, $19.2 million for the year ended December 31, 2012 and $12.2 million for the six months ended June 30, 2013. As of June 30, 2013, we had an accumulated deficit of $89.3 million. To date, we have financed our operations primarily through private placements of our preferred stock and convertible debt securities, borrowings under our credit facility with Hercules Technology Growth Capital, Inc., or Hercules, government grants and collaborations. All of our revenue to date has been collaboration revenue and government grants. We have devoted substantially all of our financial resources and efforts to developing our medicinal nanoengineering platform, identifying potential drug candidates, and conducting preclinical studies and clinical trials. We are still in the early stages of development of our drug candidates, and we have not completed development of any Accurins or other drugs. We expect to continue to incur significant expenses and operating losses for the foreseeable future. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase substantially as we:

 

   

conduct our Phase 2 clinical trials of BIND-014, our lead Accurin drug candidate, a prostate-specific membrane antigen, or PSMA, targeted Accurin that contains docetaxel, and potentially conduct pivotal clinical trials of BIND-014;

 

   

continue the research and development of our other drug candidates, including potentially in-licensing other technologies and therapeutic payloads, but excluding research and development costs of our drug candidates being developed in collaboration with Amgen, Inc., Pfizer Inc. and AstraZeneca AB, as these collaborators generally are required to pay all such development costs, including those incurred by us;

 

   

seek to enhance our medicinal nanoengineering platform and discover and develop additional drug candidates;

 

   

seek regulatory approvals for any drug candidates that successfully complete clinical trials;

 

   

potentially establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;

 

   

maintain, expand and protect our intellectual property portfolio; and

 

   

add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product development and potential future commercialization efforts and to support our transition to a public company.

To become and remain profitable, we must succeed in developing and eventually commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our drug candidates, discovering additional drug candidates, obtaining regulatory approval for these drug candidates and manufacturing, marketing and selling

 

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any products for which we may obtain regulatory approval, and establishing and managing our collaborations at various stages of each candidate’s development. We are only in the preliminary stages of most of these activities. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability.

Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. If we are required by the U.S. Food and Drug Administration, or FDA, or the European Medicines Agency, or EMA, to perform studies in addition to those currently expected, or if there are any delays in completing our clinical trials or the development of any of our drug candidates, our expenses could increase and revenue could be further delayed.

Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even continue our operations. A decline in the value of our company could also cause you to lose all or part of your investment.

We will need additional funding. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

We expect our expenses to increase in connection with our ongoing activities, particularly as we conduct our Phase 2 clinical trials of BIND-014, and continue research and development and initiate additional clinical trials of, and seek regulatory approval for, BIND-014 and other drug candidates. In addition, if we obtain regulatory approval for any of our drug candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. Furthermore, upon the closing of this offering, we expect to incur additional costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.

We believe that the net proceeds from this offering, together with our cash and cash equivalents as of June 30, 2013, borrowings available under our credit facility and research and development funding that we expect to receive under our existing collaborations, excluding any potential milestone payments, will fund our operating expenses and capital expenditure requirements through at least mid-2015, which we expect will enable us to complete our ongoing Phase 2 clinical trials of BIND-014 in NSCLC and mCRPC and, if such trials are successful, to initiate pivotal Phase 3 trials in these indications. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Our future capital requirements will depend on many factors, including:

 

   

our collaboration agreements remaining in effect, our collaborators exercising their options under these agreements, our ability to achieve milestones under these agreements and our entering into additional collaboration agreements;

 

   

the progress and results of our clinical trials of BIND-014;

 

   

the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other drug candidates;

 

   

the costs, timing and outcome of regulatory review of our drug candidates;

 

   

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

 

   

the revenue, if any, received from commercial sales of our drug candidates for which we receive marketing approval;

 

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the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and

 

   

the extent to which we acquire or in-license other products and technologies.

Identifying potential drug candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain regulatory approval and achieve product sales. In addition, our drug candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives. Adequate additional financing may not be available to us on acceptable terms, or at all. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans.

Raising additional capital may cause dilution to our stockholders, including purchasers of common stock in this offering, restrict our operations or require us to relinquish rights to our technologies or drug candidates.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and license and collaboration agreements. We do not have any committed external source of funds other than research and development funding under our existing collaborations and borrowings available under our credit facility. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a common stockholder. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or drug candidates or grant licenses on terms that may not be favorable to us and/or that may reduce the value of our common stock.

Our limited operating history may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

We commenced active operations in 2007, and our operations to date have been limited to organizing and staffing our company, business planning, raising capital, developing our medicinal nanoengineering platform, identifying potential drug candidates, and conducting preclinical studies and clinical trials. All but one of our drug candidates, BIND-014, are still in preclinical development. We recently completed a portion of our Phase 1 clinical trial of BIND-014, our lead drug candidate, and are conducting two Phase 2 clinical trials for this drug candidate, but have not completed these or any other clinical trials for this or any other drug candidate. We have not yet demonstrated our ability to successfully complete any Phase 2 or pivotal clinical trials, obtain regulatory approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history.

In addition, as a young business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.

 

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

The terms of our credit facility place restrictions on our operating and financial flexibility. If we raise additional capital through debt financing, the terms of any new debt could further restrict our ability to operate our business.

We have an $8.5 million credit facility with Hercules that is secured by a lien covering substantially all of our personal property, excluding intellectual property. As of June 30, 2013, the outstanding principal balance of the loan was $4.5 million. The credit facility contains customary affirmative and negative covenants and events of default applicable to us and our subsidiaries. The affirmative covenants include, among others, covenants requiring us (and us to cause our subsidiaries) to maintain our legal existence and governmental approvals, deliver certain financial reports and maintain insurance coverage. The negative covenants include, among others, restrictions on us and our subsidiaries transferring collateral, incurring additional indebtedness, engaging in mergers or acquisitions, paying dividends or making other distributions, making investments, creating liens, selling assets, and suffering a change in control, in each case subject to certain exceptions. If we default under the facility, the lender may accelerate all of our repayment obligations and take control of our pledged assets, potentially requiring us to renegotiate our agreement on terms less favorable to us or to immediately cease operations. Further, if we are liquidated, the lender’s right to repayment would be senior to the rights of the holders of our common stock to receive any proceeds from the liquidation. The lender could declare a default upon the occurrence of any event that it interprets as a material adverse effect as defined under the credit facility, thereby requiring us to repay the loan immediately or to attempt to reverse the declaration of default through negotiation or litigation. Any declaration by the lender of an event of default could significantly harm our business and prospects and could cause the price of our common stock to decline. If we raise any additional debt financing, the terms of such additional debt could further restrict our operating and financial flexibility.

Risks Related to the Discovery and Development of Our Drug Candidates

We may not be successful in our efforts to use and expand our medicinal nanoengineering platform to build a pipeline of drug candidates and develop marketable drugs.

We are using our proprietary medicinal nanoengineering platform to develop BIND-014 and additional Accurins, with an initial focus on the treatment of various types of cancer. While we believe our preclinical and Phase 1 clinical data to date, together with our established collaborations, has validated our platform to a degree, we are at a very early stage of development and our platform has not yet, and may never lead to, approvable or marketable drugs. Even if we are successful in continuing to build our pipeline, the potential drug candidates that we identify may not be suitable for clinical development, including as a result of their harmful side effects, limited efficacy or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance. If we do not successfully develop and commercialize drug candidates based upon our technological approach, we will not be able to obtain product or collaboration revenues in future periods, which likely would result in significant harm to our financial position and adversely affect our stock price.

We are very early in our development efforts and have only one drug candidate in clinical development. All of our other drug candidates are still in preclinical development. If we or our collaborators are unable to successfully develop and commercialize drug candidates or experience significant delays in doing so, our business will be materially harmed.

We are very early in our development efforts and have only one drug candidate, BIND-014, in clinical development. All of our other drug candidates are still in preclinical development. We have invested substantially all of our efforts and financial resources in developing our medicinal nanoengineering platform,

 

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identifying potential drug candidates, and conducting preclinical studies and clinical trials. Our ability to generate product revenues, which we do not expect will occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of our drug candidates. The success of our drug candidates will depend on several factors, including the following:

 

   

completion of preclinical studies and clinical trials with positive results;

 

   

receipt of marketing approvals from applicable regulatory authorities;

 

   

obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our drug candidates;

 

   

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

 

   

launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;

 

   

successfully maintaining existing collaborations and entering into new ones throughout the development process as appropriate, from preclinical studies through to commercialization;

 

   

acceptance of the products, if and when approved, by patients, the medical community and third-party payors;

 

   

effectively competing with other therapies;

 

   

obtaining and maintaining coverage and adequate reimbursement by third-party payors, including government payors, for our drug candidates;

 

   

protecting our rights in our intellectual property portfolio;

 

   

maintaining a continued acceptable safety profile of the products following approval; and

 

   

maintaining and growing an organization of scientists and business people who can develop and commercialize our products and technology.

If we or our collaborators do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to successfully develop and commercialize our drug candidates, which would materially harm our business.

Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our drug candidates.

All but one of our drug candidates are in preclinical development, with one, BIND-014, in Phase 2 clinical development, and their risk of failure is high. It is impossible to predict when or if any of our drug candidates will prove effective and safe in humans or will receive regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of any drug candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our drug candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failed clinical trial can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. For example, the preliminary efficacy signal in our Phase 1 clinical trial of BIND-014 was observed in only a small number of patients in a single-arm, open-label setting and might not be achieved by any other patients treated with BIND-014 in future trials. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their drug candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.

 

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We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our drug candidates, including:

 

   

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

 

   

we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;

 

   

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

 

   

the number of patients required for clinical trials of our drug candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate;

 

   

our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;

 

   

we may have to suspend or terminate clinical trials of our drug candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;

 

   

regulators or institutional review boards may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;

 

   

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

 

   

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

 

   

our drug candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boards to suspend or terminate the trials;

 

   

regulators may revise the requirements for approving our drug candidates, or such requirements may not be as we anticipate; and

 

   

regarding trials managed by our existing or any future collaborators, our collaborators may face any of the above issues, and may conduct clinical trials in ways they view as advantageous to them but potentially suboptimal for us.

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

 

   

be delayed in obtaining marketing approval for our drug candidates;

 

   

lose the support of collaborators, requiring us to bear more of the burden of development of certain compounds;

 

   

not obtain marketing approval at all;

 

   

obtain marketing approval in some countries and not in others;

 

   

obtain approval for indications or patient populations that are not as broad as we intend or desire;

 

   

obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;

 

   

be subject to additional post-marketing testing requirements; or

 

   

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

 

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We are currently conducting two Phase 2 clinical trials to evaluate the level of clinical activity of BIND-014 in non-small cell lung cancer, or NSCLC, and metastatic castrate-resistant prostate cancer, or mCRPC. If we obtain favorable results in these trials, we plan to initiate pivotal trials of this drug candidate in early 2015 in both mCRPC and second-line NSCLC. We also may initiate clinical trials in other types of cancer. However, we cannot provide any assurance that we will successfully complete our ongoing Phase 2 clinical trials and be able to initiate pivotal clinical trials for this drug candidate for either or both types of cancer. The results of our Phase 2 clinical trials could yield negative or ambiguous results. Since this is our most advanced drug candidate, such results could adversely affect future development plans, collaborations and our stock price.

Our product development costs will increase if we experience delays in clinical testing or marketing approvals. We do not know whether any of our preclinical studies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant preclinical or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our drug candidates or allow our competitors to bring products to market before we do, potentially impairing our ability to successfully commercialize our drug candidates and harming our business and results of operations.

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

We may not be able to initiate or continue clinical trials for our drug candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In addition, some of our competitors have ongoing clinical trials for drug candidates that treat the same indications as our drug candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ drug candidates.

Patient enrollment is affected by other factors including:

 

   

the severity of the disease under investigation;

 

   

the patient eligibility criteria for the study in question;

 

   

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

 

   

the efforts to facilitate timely enrollment in clinical trials;

 

   

our payments for conducting clinical trials;

 

   

the patient referral practices of physicians;

 

   

the ability to monitor patients adequately during and after treatment; and

 

   

the proximity and availability of clinical trial sites for prospective patients.

We expect that the Phase 2 clinical trials of BIND-014 we initiated in the second quarter of 2013 will take approximately 12 months to enroll; however, we cannot assure you that our enrollment assumptions are correct based on the above factors. Our inability to enroll a sufficient number of patients for our clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for our drug candidates, which would cause the value of our company to decline and limit our ability to obtain additional financing.

If serious adverse or unacceptable side effects are identified during the development of our drug candidates or we observe limited efficacy, we may need to abandon or limit our development of some of our drug candidates.

If our drug candidates are associated with undesirable side effects in clinical trials, have limited efficacy or have characteristics that are unexpected, we may need to abandon their development or limit development to

 

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more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective. For example, of the 28 patients dosed once every three weeks, or Q3W, in our ongoing Phase 1 clinical trial of BIND-014, 25 patients experienced a treatment-related adverse event, with one such event resulting in death. Three patients discontinued treatment as a result of treatment-related adverse events. The most common adverse event experienced by ten patients in this study was neutropenia, a low number of white blood cells, which is frequently associated with docetaxel as well as many other cancer drugs. The one death in the trial was an elderly patient with advanced biliary cancer and a biliary stent who was treated with BIND-014 at 75 mg/m2 dosing and developed sepsis as a consequence of neutropenia, which has previously been observed in clinical studies of patients receiving docetaxel. Other treatment-related adverse events included fatigue, diarrhea, anemia, hair loss, infusion related reaction, dehydration, nausea and vomiting. These treatment-related adverse events and their frequency are generally consistent with the treatment-related adverse events associated with docetaxel as well as many other cancer drugs. In light of the similarity with other FDA-approved cancer therapeutics, we believe our Phase 1 results to date suggest an acceptable safety profile at this stage of development. However, many compounds that initially showed promise in early stage testing for treating cancer have later been found to cause side effects that prevented further development of the compound.

Risks Related to Our Dependence on Third Parties

Our existing collaborations are important to our business, and future collaborations may also be important to us. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could be adversely affected.

We have entered into collaborations with other biopharmaceutical companies to develop Accurins based on therapeutic payloads from their product pipelines, and such collaborations currently represent a significant portion of our product pipeline. Our collaboration and license agreements include those we have announced with Amgen, AstraZeneca and Pfizer, and others that we have not announced. These collaborations also have provided us with important funding for our development programs and we expect to receive additional funding under these collaborations in the future. Our existing collaborations, and any future collaborations we enter into, may pose a number of risks, including the following:

 

   

collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;

 

   

collaborators may not perform their obligations as expected;

 

   

collaborators may not pursue development and commercialization of any drug candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;

 

   

collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing;

 

   

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or drug 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, which may cause collaborators to cease to devote resources to the commercialization of our drug candidates;

 

   

a collaborator with marketing and distribution rights to one or more of our drug candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products;

 

   

disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development

 

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or commercialization of drug candidates, might lead to additional responsibilities for us with respect to drug candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

 

   

collaborators may not properly maintain or defend 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;

 

   

collaborators may infringe 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, we would potentially lose the right to pursue further development or commercialization of the applicable drug candidates;

 

   

collaborators may learn about our technology and use this knowledge to compete with us in the future;

 

   

results of collaborators’ preclinical or clinical studies could produce results that harm or impair other products using our technology;

 

   

there may be conflicts between different collaborators that could negatively affect those collaborations and potentially others; and

 

   

the number and type of our collaborations could adversely affect our attractiveness to future collaborators or acquirers.

If our collaborations do not result in the successful development and commercialization of products or if one of our collaborators terminates its agreement with us, or in the case of Amgen or Pfizer, elects not to exercise its option under the collaboration agreement, we may not receive any future research and development funding or milestone or royalty payments under the collaboration. If we do not receive the funding we expect under these agreements, our continued development of our medicinal nanoengineering platform and drug candidates could be delayed and we may need additional resources to develop additional drug candidates. All of the risks relating to product development, regulatory approval and commercialization described in this prospectus also apply to the activities of our collaborators and there can be no assurance that our collaborations will produce positive results or successful products on a timely basis or at all.

Under our collaboration agreement with Amgen, Amgen has the right to pay us an annual exclusivity fee to prohibit us from developing a drug candidate against the same molecular target as Amgen’s drug candidate. In addition, for a specified period of time following the execution of our collaboration agreement with AstraZeneca, we may not develop or commercialize a compound against the same molecular target as AstraZeneca’s drug candidate. As a result, our ability to enter into collaboration agreements for additional drug candidates against these targets is significantly limited until the end of the periods specified in our collaboration agreements with Amgen and AstraZeneca. These restrictions may have the effect of preventing us from undertaking development and other efforts that may appear to be attractive to us.

Additionally, subject to its contractual obligations to us, if a collaborator of ours is involved in a business combination or otherwise changes its business priorities, the collaborator might deemphasize or terminate the development or commercialization of any drug candidate licensed to it by us. If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities and our stock price could be adversely affected.

We may in the future determine to collaborate with additional pharmaceutical and biotechnology companies for development and potential commercialization of therapeutic products. We face significant competition in seeking appropriate collaborators. Our ability to 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. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may not be able to access therapeutic payloads that would be suitable to development with our platform, have to curtail the

 

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development of a drug candidate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our drug candidates or bring them to market or continue to develop our product platform and our business may be materially and adversely affected.

We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials.

We currently rely on third-party clinical research organizations, or CROs, to conduct our ongoing Phase 1 and Phase 2 clinical trials of BIND-014 and do not plan to independently conduct clinical trials of our other drug candidates. We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct and manage our clinical trials. These agreements might terminate for a variety of reasons, including a failure to perform by the third parties. If we need to enter into alternative arrangements, that would delay our 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 responsibilities. For example, we will remain 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 regulatory standards, commonly referred to as good clinical practices, or GCPs, 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. Other countries’ regulatory agencies also have requirements for clinical trials with which we must comply. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our drug candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our drug candidates.

We also expect to rely on other third parties to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our distributors could delay clinical development or marketing approval of our drug candidates or commercialization of our products, producing additional losses and depriving us of potential product revenue.

We contract with third parties for the manufacture of our drug candidates for preclinical and clinical testing and expect to continue to do so for the foreseeable future. This reliance on third parties increases the risk that we will not have sufficient quantities of our drug candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.

We have a pilot manufacturing facility at our Cambridge location where we conduct process development, scale-up activities and assemble the manufacturing equipment for use in the manufacture of Accurins. However, we do not have any manufacturing facilities that meet the FDA’s current good manufacturing practices, or cGMP, requirements for the production of any drug candidates used in humans. We rely, and expect to continue to rely, on third parties for the manufacture of our drug candidates for preclinical and clinical testing, as well as for commercial manufacture if any of our drug candidates receive marketing approval. This reliance on third

 

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parties increases the risk that we will not have sufficient quantities of our drug candidates on a timely basis or at all or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.

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

 

   

failure of third-party manufacturers to comply with regulatory requirements and maintain quality assurance;

 

   

breach of the manufacturing agreement by the third party;

 

   

failure to manufacture our product according to our specifications;

 

   

failure to manufacture our product according to our schedule or at all;

 

   

misappropriation of our proprietary information, including our trade secrets and know-how; and

 

   

termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.

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

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

Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval. We do not currently have arrangements in place for redundant supply or a second source for required raw materials used in the manufacture of our drug candidates, including the polymers used in our Accurins, or for the manufacture of finished BIND-014 product. If our current contract manufacturers cannot perform as agreed, we may be required to replace such manufacturers and we may be unable to replace them on a timely basis or at all. In particular, there are a very few manufacturers capable of supplying the polymers used in our Accurins.

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

Risks Related to Regulatory Approval of Our Drug Candidates and Other Legal Compliance Matters

If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our drug candidates or will not be able to do so as soon as anticipated, and our ability to generate revenue will be materially impaired.

Our drug candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by the EMA and similar regulatory authorities outside the United States. Failure to obtain marketing approval for a drug candidate will prevent us from commercializing the drug candidate. We have not received approval to market any of our drug candidates from regulatory authorities in any jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain

 

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marketing approvals and expect to rely on third parties to assist us in this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the drug candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities. Our drug candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use. For example, new cancer drugs frequently are indicated only for patient populations that have not responded to an existing therapy or have relapsed. If any of our drug candidates with a cancer indication receives marketing approval, the accompanying label may limit the approved use of our drug in this way, which could limit sales of the product.

The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many years. If additional clinical trials are required for certain jurisdictions, these trials can vary substantially based upon a variety of factors, including the type, complexity and novelty of the drug candidates involved, and may ultimately be unsuccessful. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review process for each submitted product application, may cause delays in the review and approval of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept a marketing application as deficient or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a drug 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.

Although the FDA and other regulatory authorities have approved nanotechnology-based therapeutics in the past, they are monitoring whether nanotechnology-based therapeutics pose any specific health and human safety risks. While they have not issued any regulations to date, it is possible that the FDA and other regulatory authorities could issue regulations in the future regarding nanotechnology-based therapeutics that could adversely affect our drug candidates.

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

If the FDA does not conclude that BIND-014 satisfies the requirements for approval under the Section 505(b)(2) regulatory approval pathway, or if the requirements for approval of BIND-014 under Section 505(b)(2) are not as we expect, the approval pathway for BIND-014 will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and in any case may not be successful.

We intend to seek FDA approval for BIND-014 through the Section 505(b)(2) regulatory pathway. Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, or FDCA, would allow a new drug application, or NDA, we submit to the FDA to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of an approved drug product, which could expedite the development program for BIND-014 by potentially decreasing the amount of clinical data that we would need to generate in order to obtain FDA approval. If the FDA does not allow us to pursue the Section 505(b)(2) regulatory pathway as anticipated, we may need to conduct additional clinical trials, provide additional data and information, and meet additional standards for product approval. If this were to occur, the time and financial resources required to obtain FDA approval for BIND-014, and complications and risks associated with regulatory approval of BIND-014, would likely substantially increase. Moreover, inability to pursue the Section 505(b)(2) regulatory pathway may result in new competitive products reaching the market more quickly than BIND-014, which would likely

 

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materially adversely impact our competitive position and prospects. Even if we are able to utilize the Section 505(b)(2) regulatory pathway, there is no guarantee this will ultimately lead to accelerated product development or earlier approval.

In addition, the pharmaceutical industry is highly competitive, and Section 505(b)(2) NDAs are subject to special requirements designed to protect the patent rights of sponsors of previously approved drugs that may be referenced in a Section 505(b)(2) NDA. These requirements may give rise to patent litigation and mandatory delays in approval of our NDA for up to 30 months or longer depending on the outcome of any litigation. Further, it is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of a new product. Even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition.

Moreover, even if BIND-014 is approved under Section 505(b)(2), the approval may be subject to limitations on the indicated uses for which the products may be marketed or to other conditions of approval, or may contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the products.

In the European Economic Area, or EEA (composed of the 27 European Union, or EU, Member States plus Iceland, Liechtenstein and Norway), we intend to seek approval for BIND-014 under the hybrid application pathway of the EU Centralized Procedure.

The hybrid pathway is available for (i) products that do not fall under the strict definition of a generic medicinal product, (ii) whose bioequivalence to the reference product cannot be demonstrated through bioavailability studies, or (iii) whose active substances, therapeutic indications, strength, pharmaceutical form or route of administration, differs from that of the reference product. Hybrid applications may rely in part on the results of preclinical tests and clinical trials contained in the authorization dossier of the reference product, which will however need to be supplemented with additional data. We have not engaged in pre-submission discussions with the EMA to determine the eligibility of the centralized hybrid process for BIND-014. If the EMA does not allow us to pursue the centralized hybrid pathway as anticipated, we may need to conduct additional clinical trials, provide additional data and information, and meet additional standards to have BIND-014 authorized in the EEA.

A fast track designation by the FDA may not actually lead to a faster development or regulatory review or approval process.

We may seek fast track designation for some of our drug candidates. If a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for this condition, the drug sponsor may apply for FDA fast track designation. The FDA has broad discretion whether or not to grant this designation, and even if we believe a particular drug candidate is eligible for this designation, we cannot assure you 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.

We may not be able to obtain orphan drug exclusivity for our drug candidates.

Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States.

 

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Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the EMA or the FDA from approving another marketing application for the same drug for that time period. The applicable period is seven years in the United States and ten years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets the criteria for orphan drug designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified. Orphan drug exclusivity may be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition.

Even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs can be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.

A breakthrough therapy designation by the FDA for our drug candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our drug candidates will receive marketing approval.

We may seek a breakthrough therapy designation for some of our drug 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. 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 accelerated approval.

Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our drug candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. The availability of breakthrough therapy designation was established recently with the passage of the Food and Drug Administration Safety and Innovation Act of 2012, and the FDA has not yet released additional guidance as to the criteria it uses in designating drugs as breakthrough therapies. As a result, we cannot be sure that our evaluation of our drugs as qualifying for breakthrough therapy designation will meet the FDA’s expectations. In any event, the receipt of a breakthrough therapy designation for a drug candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our drug candidates qualify as breakthrough therapies, the FDA may later decide that the products no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Failure to obtain marketing approval in international jurisdictions would prevent our drug candidates from being marketed abroad.

In order to market and sell our products in the European Union and many other jurisdictions, we or our collaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval in foreign countries may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We or our

 

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collaborators may not obtain approvals for our drug candidates from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any market.

Any drug candidate for which we obtain marketing approval could be subject to post-marketing restrictions or withdrawal from the market and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.

Any drug candidate for which we obtain marketing approval, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. Even if marketing approval of a drug candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including the requirement to implement a risk evaluation and mitigation strategy, or REMS, which could include requirements for a restricted distribution system. If any of our drug candidates receives marketing approval, the accompanying label may limit the approved use of our drug, which could limit sales of the product.

The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of our approved products. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use and if we market our products outside of their approved indications, we may be subject to enforcement action for off-label marketing. Violations of the FDCA relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state health care fraud and abuse laws, as well as state consumer protection laws.

In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including:

 

   

litigation involving patients taking our drug;

 

   

restrictions on such products, manufacturers or manufacturing processes;

 

   

restrictions on the labeling or marketing of a product;

 

   

restrictions on product distribution or use;

 

   

requirements to conduct post-marketing studies or clinical trials;

 

   

warning letters;

 

   

withdrawal of the products from the market;

 

   

refusal to approve pending applications or supplements to approved applications that we submit;

 

   

recall of products;

 

   

fines, restitution or disgorgement of profits or revenues;

 

   

suspension or withdrawal of marketing approvals;

 

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damage to relationships with existing and potential collaborators;

 

   

unfavorable press coverage and damage to our reputation;

 

   

refusal to permit the import or export of our products;

 

   

product seizure; or

 

   

injunctions or the imposition of civil or criminal penalties.

Noncompliance with similar European Union requirements regarding safety monitoring or pharmacovigilance can also result in significant financial penalties. Similarly, failure to comply with U.S. and foreign regulatory requirements regarding the development of products for pediatric populations and the protection of personal health information can also lead to significant penalties and sanctions.

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

Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any drug candidates for which we obtain marketing approval. Our future arrangements with third-party payors, physicians and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute any products for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:

 

   

the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;

 

   

the federal False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

 

   

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

 

   

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

 

   

federal law requires applicable manufacturers of covered drugs to report payments and other transfers of value to physicians and teaching hospitals, with data collection beginning in August 2013; and

 

   

analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.

Some 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 and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures. State and foreign laws 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.

 

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Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our drug candidates and affect the prices we may obtain.

In the United States and some foreign 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 drug candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any drug candidates for which we obtain marketing approval.

In the United States, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, or the MMA, changed the way Medicare covers and pays for pharmaceutical products. The legislation expanded Medicare coverage for drug purchases by the elderly and introduced a new reimbursement methodology based on average sales prices for physician-administered drugs. In addition, this legislation provided authority for limiting the number of drugs that will be covered in any therapeutic class. Cost reduction initiatives and other provisions of this legislation could decrease the coverage and price that we receive for any approved products. While the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates. Therefore, any reduction in reimbursement that results from the MMA may result in a similar reduction in payments from private payors.

More recently, in 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act, or collectively the PPACA, a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

Among the provisions of the PPACA of importance to our potential drug candidates are the following:

 

   

an annual, nondeductible fee payable by any entity that manufactures or imports specified branded prescription drugs and biologic agents;

 

   

an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;

 

   

expansion of healthcare fraud and abuse laws, including the False Claims Act and the Anti-Kickback Statute, new government investigative powers, and enhanced penalties for noncompliance;

 

   

a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point-of-sale discounts off negotiated prices;

 

   

extension of manufacturers’ Medicaid rebate liability;

 

   

expansion of eligibility criteria for Medicaid programs;

 

   

expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;

 

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new requirements to report financial arrangements with physicians and teaching hospitals;

 

   

a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and

 

   

a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

In addition, other legislative changes have been proposed and adopted since the PPACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs. This includes aggregate reductions of Medicare payments to providers up to 2% per fiscal year. On January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, or the ATRA, which delayed for another two months the budget cuts mandated by these sequestration provisions of the Budget Control Act of 2011. On March 1, 2013, the President signed an executive order implementing sequestration, and on April 1, 2013, the 2% Medicare payment reductions went into effect. The ATRA also, among other things, reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain.

We expect that the PPACA, 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 receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our drug candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.

Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.

In some countries, particularly the countries of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our drug candidate to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.

If we 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 produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury

 

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from these materials. In the event of contamination or injury resulting from our use of 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.

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. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

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.

Risks Related to the Commercialization of Our Drug Candidates

Even if any of our drug candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

If any of our drug candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For example, current cancer treatments like chemotherapy and radiation therapy are well established in the medical community, and physicians may continue to rely on these treatments. In addition, many new drugs have been recently approved and many more are in the pipeline for the same diseases for which we are developing our drug candidates. If our drug candidates do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of our drug candidates, if approved for commercial sale, will depend on a number of factors, including:

 

   

their efficacy, safety and other potential advantages compared to alternative treatments;

 

   

our ability to offer them for sale at competitive prices;

 

   

their convenience and ease of administration compared to alternative treatments;

 

   

the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

 

   

the strength of marketing and distribution support;

 

   

the availability of third-party coverage and adequate reimbursement for our drug candidates;

 

   

the prevalence and severity of their side effects; and

 

   

any restrictions on the use of our products together with other medications;

 

   

interactions of our products with other medicines patients are taking; and

 

   

inability of certain types of patients to take our product.

If we are unable to establish effective sales, marketing and distribution capabilities or enter into agreements with third parties with such capabilities, we may not be successful in commercializing our drug candidates if and when they are approved.

We do not have a sales or marketing infrastructure and have no experience in the sale, marketing or distribution of pharmaceutical products. To achieve commercial success for any product for which we obtain marketing approval, we will need to establish a sales and marketing organization or make arrangements with third parties to perform sales and marketing functions.

 

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In the future, we expect to build a focused oncology sales and marketing infrastructure to market or co-promote some of our drug candidates in the United States and potentially elsewhere, if and when they are approved. There are risks involved with establishing our own sales, marketing and distribution capabilities. For example, recruiting and training a sales force is expensive and time consuming and could delay any product launch. If the commercial launch of a drug candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

Factors that may inhibit our efforts to commercialize our products on our own include:

 

   

our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;

 

   

the inability of sales personnel to obtain access to or educate physicians on the benefits of our products;

 

   

the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

 

   

unforeseen costs and expenses associated with creating an independent sales and marketing organization; and

 

   

inability to obtain sufficient coverage and reimbursement from third-party payors and governmental agencies.

Outside the United States, we expect to rely on third parties to sell, market and distribute our drug candidates. We may not be successful in entering into arrangements with such third parties or may be unable to do so on terms that are favorable to us. In addition, our product revenues and our profitability, if any, may be lower if we rely on third parties for these functions than if we were to market, sell and distribute any products that we develop ourselves. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our drug candidates.

We face substantial competition, which may result in others discovering, developing or commercializing competing products before or more successfully than we do.

The development and commercialization of new drug products is highly competitive. We face competition with respect to our current drug candidates, and will face competition with respect to any drug candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we are developing our drug candidates. Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources, established presence in the market and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.

 

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Smaller and other early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific, sales and marketing and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. Generic products are currently on the market, including the therapeutics payload in BIND-014, for the indications that we are pursuing, and additional products are expected to become available on a generic basis over the coming years. If our drug candidates achieve marketing approval, we expect that they will be priced at a significant premium over competitive generic products.

The most common methods of treating patients with cancer are surgery, radiation and drug therapy, including chemotherapy and targeted drug therapy. There are a variety of available drug therapies marketed for solid tumors. In many cases, these drugs are administered in combination to enhance efficacy. Some of these drugs are branded and subject to patent protection, and others are available on a generic basis, including the therapeutic payload contained in BIND-014. Many of these approved drugs are well established therapies and are widely accepted by physicians, patients and third-party payors. There are also a number of products in late stage clinical development to treat solid tumors. These products in development may provide efficacy, safety, convenience and other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for BIND-014 or any other drug candidate for which we obtain marketing approval.

Specifically, current second-line treatments for NSCLC include docetaxel and other chemotherapy agents such as gemcitabine and vinorelbine, as well as molecularly-targeted therapies such as erlotinib and gefitinib, which are used to treat patients with mutations in epidermal growth factor receptor, or EGFR, and crizotinib, which is used in the small subset of patients that have a mutation in anaplastic lymphoma kinase, or ALK. In addition, two monoclonal antibodies, Bristol-Myers Squibb’s nivolumab that targets PD-1, and F. Hoffmann-La Roche Ltd’s MPDL3280A that targets PD-L1, are currently in Phase 2 clinical trials for NSCLC. Both are immunomodulators that block the activation of programmed cell death receptor. In mCRPC, in addition to first-line chemotherapy agents such as docetaxel, the treatment paradigm is evolving to include use of hormonal therapies such as abiraterone and enzalutamide prior to the administration of chemotherapies, which therapies are currently mainly used in the post-chemotherapy setting. Other similar drugs are also being developed. Cabazitaxel (marketed as Jevtana), a second-line taxane chemotherapeutic, is also being tested in clinical studies against docetaxel for efficacy in mCRPC. In addition, other companies are developing therapies targeting PSMA to treat mCRPC, including an antibody-drug conjugate, or ADC, by Progenics Pharmaceuticals, Inc. and a Bispecific T Cell Engager, or BITE, antibody by Bayer Healthcare in collaboration with Amgen. We also face competition from numerous companies utilizing other nanomedicine platforms to develop targeted therapies, including platforms focused on albumin nanoparticles, liposomes and polymeric nanoparticles.

Even if we are able to commercialize any drug candidates, the products may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some

 

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countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control, including possible price reductions, even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more drug candidates, even if our drug candidates obtain marketing approval.

Our ability to commercialize any drug candidates successfully also will depend in part on the extent to which coverage and reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for drugs. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be sufficient to generate a profit. Reimbursement may affect the demand for, or the price of, any drug candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any drug candidate for which we obtain marketing approval.

There may be significant delays in obtaining reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

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

We face an inherent risk of product liability exposure related to the testing of our drug candidates in human clinical trials and will face an even greater risk if we commercially sell any products that we may develop. If we cannot successfully defend ourselves against claims that our drug candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

 

   

decreased demand for any drug candidates or products that we may develop;

 

   

injury to our reputation and significant negative media attention;

 

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withdrawal of clinical trial participants;

 

   

significant costs to defend the related litigation;

 

   

substantial monetary awards to trial participants or patients;

 

   

loss of revenue;

 

   

reduced resources of our management to pursue our business strategy; and

 

   

the inability to commercialize any products that we may develop.

We currently hold $10.0 million in product liability insurance coverage in the aggregate, with a per incident limit of $10.0 million, which may not be adequate to cover all liabilities that we may incur. We may need to increase our insurance coverage as we expand our clinical trials or if we commence commercialization of our drug candidates. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Risks Related to Employee Matters and Managing Growth and Other Risks Related to Our Business

Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.

We are highly dependent on Scott Minick, our President and Chief Executive Officer, as well as the other principal members of our management, scientific and clinical team. Although we have entered into employment letter agreements with our executive officers, each of them may terminate their employment with us at any time. We do not maintain “key person” insurance for any of our executives or other employees.

Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel will also be critical to our success. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory approval of and commercialize products. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development 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. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growth strategy will be limited.

We expect to expand our development and regulatory capabilities and potentially implement sales, marketing and distribution capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.

We expect to experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of drug development, regulatory affairs, manufacturing and, if any of our drug candidates receives marketing approval, sales, marketing and distribution. To manage our anticipated future growth, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel. Due to our limited financial resources and the limited experience of our management team in managing a company with such anticipated growth, we may not

 

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be able to effectively manage the expansion of our operations or recruit and train additional qualified personnel. The expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.

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

In addition to our U.S. operations, we have operations in Russia through our wholly-owned subsidiary, BIND (RUS) LLC, and may have other such international operations in the future. We face risks associated with our operations in Russia, including possible unfavorable regulatory, pricing and reimbursement, legal, political, tax and labor conditions, which could harm our business. We are also conducting and in the future plan to continue to conduct clinical trials of drug candidates in Russia. We are subject to numerous risks associated with international business activities in Russia and elsewhere, including:

 

   

compliance with differing or unexpected regulatory requirements for our products;

 

   

compliance with Russian laws with respect to our BIND (RUS) LLC subsidiary;

 

   

difficulties in staffing and managing foreign operations;

 

   

foreign government taxes, regulations and permit requirements;

 

   

U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;

 

   

economic weakness, including inflation, natural disasters, war, events of terrorism or political instability in particular foreign countries;

 

   

fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenues;

 

   

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

 

   

changes in diplomatic and trade relationships; and

 

   

challenges in enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States.

These and other risks associated with our international operations in Russia and elsewhere may materially adversely affect our business, financial condition and results of operations.

Our business and operations would suffer in the event of system failures.

Despite the implementation of security measures, our internal computer systems and those of our current and future contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from 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. Likewise, we rely on third parties to manufacture our drug candidates and conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and commercialization of our drug candidates could be delayed.

 

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Risks Related to Our Intellectual Property

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

Our success depends in large part on our ability to obtain and maintain patent and other intellectual property protection in the United States and other countries with respect to our proprietary technology and products. We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our novel technologies and drug candidates.

The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost, in a timely manner, or in all jurisdictions. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Moreover, in some circumstances, we do not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we license from third parties. We may also require the cooperation of our licensors in order to enforce the licensed patent rights, and such cooperation may not be provided. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the United States and we may fail to seek or obtain patent protection in all major markets. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our owned patents or pending patent applications, or that we were the first to file for patent protection of such inventions, nor can we know whether those from whom we license patents were the first to make the inventions claimed or were the first to file. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection.

Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to United States patent law. These include provisions that affect the way patent applications are prosecuted and may also affect patent litigation. The U.S. Patent and Trademark Office, or U.S. PTO, recently developed new regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular, the first to file provisions, only became effective on March 16, 2013. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of our business. However, the Leahy-Smith Act 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 and financial condition.

Moreover, we may be subject to a third-party preissuance submission of prior art to the U.S. PTO, or become involved in opposition, derivation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties

 

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to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future drug candidates.

Even if our owned and licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products. Given the amount of time required for the development, testing and regulatory review of new drug candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

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

Competitors may infringe our issued patents or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us alleging that we infringe their intellectual property. In addition, in a patent infringement proceeding, a court may decide that a patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly, which could adversely affect us and our collaborators.

Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

Our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and sell our drug candidates and use our proprietary technologies without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. While no such litigation has been brought against us and we have not been held by any court to have infringed a third party’s intellectual property rights, we cannot guarantee that our technology, products or use of our products do not infringe third-party patents. It is also possible that we have failed to identify relevant third-party patents or applications. For example, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States remain confidential until patents issue. Patent applications in the United States and elsewhere are published approximately 18 months after the earliest filing, which is referred to as the priority date. Therefore, patent applications covering our products or technology could have been filed by others without our knowledge. Additionally, pending patent applications which have been published can, subject to certain limitations, be later amended in a manner that could cover our technologies, our products or the use of our products.

We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference or derivation

 

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proceedings before the U.S. PTO and similar bodies in other countries. Third parties may assert infringement claims against us based on existing intellectual property rights and intellectual property rights that may be granted in the future. With respect to BIND-014, we are aware of a third-party U.S. patent application that contains claims related to a formulation of a nanoparticle composition. We have an issued U.S. patent and pending non-U.S. patent applications claiming similar subject matter, and we believe our patents and patent applications have an earlier priority filing date. However, these patents and applications are subject to U.S. laws that awards patents to the first party to invent the claimed invention, rather than the first party to file a patent application. The possibility exists for an interference proceeding between our issued patent and this third-party patent application to determine the earliest party to invent the composition. Although we believe it unlikely, the possibility exists that this third-party patent application could win such an interference procedure and obtain claims which cover this formulation of a nanoparticle composition.

If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our products and technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our drug candidates or force us to cease some of our business operations, which could materially harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.

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 noncompliance with these requirements.

Periodic maintenance fees on any issued patent are due to be paid to the U.S. PTO and foreign patent agencies in several stages over the lifetime of the patent. The U.S. PTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Noncompliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. In such an event, our competitors might be able to enter the market, which would have a material adverse effect on our business.

If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our business.

We are party to multiple license agreements that impose, and we may enter into additional licensing and funding arrangements with third parties that may impose, diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. Under our existing licensing agreements, we are obligated to pay royalties on net product sales of drug candidates or related technologies to the extent they are covered by the agreement. If we fail to comply with our obligations under current or future license agreements, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market any product that is covered by these agreements or may face other penalties under the agreements. Such an occurrence could materially adversely affect the value of drug candidates being developed using rights licensed to us under any such agreement. Termination of these

 

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agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology.

We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees 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 do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that these employees or we have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. Litigation may be necessary to defend against these claims.

In addition, while it is our policy to require our employees and contractors who may be involved in the development 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 develops intellectual property that we regard as our own. Our and their assignment agreements may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to management.

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

Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could compromise our ability to compete in the marketplace.

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

In addition to seeking patents for some of our technology and drug candidates, we also rely on trade secrets, including unpatented know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, 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, contract manufacturers, consultants, advisors and other third parties. We also seek to enter into confidentiality and invention or patent assignment agreements with our employees and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Our trade secrets may also be obtained by third parties by other means, such as breaches of our physical or computer

 

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security systems. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret 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. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor, our competitive position would be harmed.

Risks Related to Our Common Stock and this Offering

After this offering, our executive officers, directors and principal stockholders, if they choose to act together, will continue to have the ability to control or significantly influence all matters submitted to stockholders for approval.

Upon the closing of this offering, based on the number of shares of common stock outstanding as of June 30, 2013, our executive officers, directors and stockholders who owned more than 5% of our outstanding common stock before this offering and their respective affiliates will, in the aggregate, hold shares representing approximately 55.6% of our outstanding voting stock, or 61.9% of our outstanding voting stock if our current stockholders purchase all of the approximately $14.7 million in shares of common stock they have indicated an interest in purchasing in this offering, based on an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus. As a result, if these stockholders were to choose to act together, they would be able to control or significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs. For example, these persons, if they choose to act together, would control or significantly influence the election of directors and approval of any merger, consolidation or sale of all or substantially all of our assets. This concentration of ownership control may:

 

   

delay, defer or prevent a change in control;

 

   

entrench our management and the board of directors; or

 

   

impede a merger, consolidation, takeover or other business combination involving us that other stockholders may desire.

If you purchase shares of common stock in this offering, you will suffer immediate dilution of your investment.

We expect the initial public offering price of our common stock to be substantially higher than the net tangible book value per share of our common stock. Therefore, if you purchase shares of our common stock in this offering, you will pay a price per share that substantially exceeds our net tangible book value per share after this offering. To the extent shares subsequently are issued under outstanding options or warrants, you will incur further dilution. Based on an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, you will experience immediate dilution of $10.43 per share, representing the difference between our pro forma as adjusted net tangible book value per share, which gives effect to this offering, and the assumed initial public offering price. In addition, purchasers of common stock in this offering will have contributed approximately 45.4% of the aggregate price paid by all purchasers of our stock but will own only approximately 29.8% of our common stock outstanding after this offering.

An active trading market for our common stock may not develop.

Prior to this offering, there has been no public market for our common stock. The initial public offering price for our common stock will be determined through negotiations with the underwriters. Although our common stock has been approved for listing on the NASDAQ Global Select Market, an active trading market for our shares may never develop or be sustained following this offering. If an active market for our common stock does not develop, it may be difficult for you to sell shares you purchase in this offering without depressing the market price for the shares or at all.

 

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The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock in this offering.

Our stock price is likely to be volatile. The stock market in general and the market for smaller biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your common stock at or above the initial public offering price. The market price for our common stock may be influenced by many factors, including:

 

   

the success of competitive products or technologies;

 

   

results of clinical trials of our drug candidates or those of our competitors;

 

   

developments related to our existing or any future collaborations;

 

   

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

 

   

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

 

   

the recruitment or departure of key personnel;

 

   

the level of expenses related to any of our drug candidates or clinical development programs;

 

   

the results of our efforts to discover, develop, acquire or in-license additional drug candidates or products;

 

   

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

 

   

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

 

   

changes in the structure of healthcare payment systems;

 

   

market conditions in the pharmaceutical and biotechnology sectors;

 

   

general economic, industry and market conditions; and

 

   

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

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

Our management will have broad discretion in the application of the net proceeds from this offering and could spend the proceeds in ways that do not improve our results of operations or enhance the value of our common stock. We intend to use the net proceeds of this offering to fund development of BIND-014, and for working capital and general corporate purposes. However, our use of these proceeds may differ substantially from our current plans. The failure by our management to apply these funds effectively could result in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and delay the development of our drug candidates. Pending their use, we may invest the net proceeds from this offering in a manner that does not produce income or that loses value.

A significant portion of our total outstanding shares are eligible to be sold into the market in the near future, which could cause the market price of our common stock to drop significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. After this offering, we will have outstanding 15,777,322 shares of common stock based on the number of shares outstanding as of June 30, 2013. This includes the shares that we are selling in this offering, which may be resold in the public market immediately without restriction, unless purchased by our affiliates or

 

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existing stockholders. The remaining 11,077,322 shares are currently restricted as a result of securities laws or lock-up agreements but will become eligible to be sold at various times after this offering. Moreover, after this offering, holders of an aggregate of 10,317,280 shares of our common stock, including shares issuable upon the exercise of warrants, will have rights, subject to specified conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders, until such shares can otherwise be sold without restriction under Rule 144 or until the rights terminate pursuant to the terms of the investors’ rights agreement. We also intend to register all shares of common stock that we may issue under our equity compensation plans. Once we register these shares, they can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates and the lock-up agreements described in the “Underwriting” section of this prospectus.

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

We are an emerging growth company, as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and may remain an emerging growth company until the last day of the fiscal year following the fifth anniversary of the completion of this offering. However, if certain events occur prior to the end of such five-year period, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.0 billion or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to the end of such five-year period. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:

 

   

being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure;

 

   

not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;

 

   

not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;

 

   

reduced disclosure obligations regarding executive compensation; and

 

   

exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.

We have taken advantage of reduced reporting burdens in this prospectus. In particular, in this prospectus, we have provided only two years of audited financial statements and have not included all of the executive compensation related information that would be required if we were not an emerging growth company. We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be reduced or more volatile. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.

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

As a public company, and particularly after we are no longer an emerging growth company, we will incur significant legal, accounting and other expenses that we did not incur as a private company. The Sarbanes-Oxley

 

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Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of the NASDAQ Global Select Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel will need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations will increase our legal and financial compliance costs and will make some activities more time-consuming and costly. For example, we expect that these rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualified members of our board of directors.

Overall, we estimate that our incremental costs resulting from operating as a public company, including compliance with these rules and regulations, may be between $2.0 million and $4.0 million per year. However, these rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we will be required to furnish a report by our management on our internal control over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we will be engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. If we identify one or more material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline.

The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our business. We do not currently have and may never obtain research coverage by securities and industry analysts. If no or few securities or industry analysts commence coverage of us, the trading price for our stock would be negatively impacted. In the event we obtain securities or industry analyst coverage, if any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our target animal studies and operating results fail to meet the expectations of analysts, our stock price would likely decline. If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

Provisions in our restated certificate of incorporation and amended and restated bylaws and under Delaware law could make an acquisition of our company, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our restated certificate of incorporation and our amended and restated bylaws that will become effective upon the closing of this offering may discourage, delay or prevent a merger, acquisition or other change in control of our company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions could also limit the price that investors might be

 

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willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors. Among other things, these provisions include those establishing:

 

   

a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors;

 

   

no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates;

 

   

the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from filling vacancies on our board of directors;

 

   

the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the terms of those shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquirer;

 

   

the ability of our board of directors to alter our bylaws without obtaining stockholder approval;

 

   

the required approval of the holders of at least two-thirds of the shares entitled to vote at an election of directors to adopt, amend or repeal our bylaws or repeal the provisions of our restated certificate of incorporation regarding the election and removal of directors;

 

   

a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders;

 

   

the requirement that a special meeting of stockholders may be called only by the chairman of the board of directors, the chief executive officer, the president or the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and

 

   

advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect the acquirer’s own slate of directors or otherwise attempting to obtain control of us.

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of Delaware, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner. Furthermore, our restated certificate of incorporation that will become effective upon the closing of this offering specifies that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions involving actions brought against us by stockholders. We believe this provision benefits us by providing increased consistency in the application of Delaware law by chancellors particularly experienced in resolving corporate disputes, efficient administration of cases on a more expedited schedule relative to other forums and protection against the burdens of multi-forum litigation. However, the provision may have the effect of discouraging lawsuits against our directors and officers. The enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that, in connection with any applicable action brought against us, a court could find the choice of forum provisions contained in our restated certificate of incorporation to be inapplicable or unenforceable in such action.

 

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Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.

We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. In addition, our Hercules credit facility currently prohibits us from paying dividends on our equity securities, and any future debt agreements may likewise preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.

We could be subject to securities class action litigation.

In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because pharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.

 

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus contains forward-looking statements. All statements other than statements of historical facts contained in this prospectus, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations and future results of anticipated products, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.

In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this prospectus are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this prospectus and are subject to a number of risks, uncertainties and assumptions described under the sections in this prospectus entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this prospectus. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

 

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USE OF PROCEEDS

We estimate that the net proceeds to us of the sale of the common stock that we are offering will be approximately $62.7 million, assuming an initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us. If the underwriters’ option to purchase additional shares from us is exercised in full, we estimate that our net proceeds will be approximately $72.5 million. Each $1.00 increase (decrease) in the assumed initial public offering price of $15.00 per share would increase (decrease) the net proceeds to us from this offering by approximately $4.4 million, assuming the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us. Each increase (decrease) of 1.0 million in the number of shares offered by us at the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the net proceeds to us from this offering, after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, by approximately $14.0 million.

The principal purposes of this offering are to obtain additional capital to support our operations, to create a public market for our common stock and to facilitate our future access to the public equity markets. We intend to use the net proceeds from this offering to fund development of BIND-014, and for working capital and general corporate purposes.

We believe that the net proceeds from this offering, together with our cash and cash equivalents as of June 30, 2013, borrowings available under our credit facility and research and development funding that we expect to receive under our existing collaborations, excluding any potential milestone payments, will fund our operating expenses and capital expenditure requirements through at least mid-2015, which we expect will enable us to complete our ongoing Phase 2 clinical trials of BIND-014 in NSCLC and mCRPC and, if such trials are successful, to initiate pivotal Phase 3 trials in these indications, although there can be no assurance in that regard.

The amounts and timing of our actual expenditures will depend on numerous factors, including the progress of our clinical trials and other development efforts for BIND-014 and other factors described under “Risk Factors” in this prospectus, as well as the amount of cash used in our operations. We therefore cannot estimate with certainty the amount of net proceeds to be used for the purposes described above. We may find it necessary or advisable to use the net proceeds for other purposes, and we will have broad discretion in the application of the net proceeds. Pending the uses described above, we plan to invest the net proceeds from this offering in short- and intermediate-term, interest-bearing obligations, investment-grade instruments, certificates of deposit or direct or guaranteed obligations of the U.S. government.

DIVIDEND POLICY

We have never declared or paid any cash dividends on our capital stock. We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends in the foreseeable future. Any future determination related to our dividend policy will be made at the discretion of our board of directors after considering our financial condition, results of operations, capital requirements, business prospects and other factors the board of directors deems relevant, and subject to the restrictions contained in any future financing instruments. In addition, our ability to pay cash dividends is currently prohibited by the terms of our credit facility with Hercules Technology Growth Capital, Inc.

 

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CAPITALIZATION

The following table sets forth our cash and cash equivalents and capitalization as of June 30, 2013, as follows:

 

   

on an actual basis;

 

   

on a pro forma basis to reflect (1) the automatic conversion of 583,333 shares of our Series BRN preferred stock into 222,646 shares of our common stock, which occurred in August 2013 upon the initial filing of the registration statement of which this prospectus is a part, (2) the automatic conversion of all outstanding shares of our preferred stock into 8,515,439 shares of common stock immediately prior to the closing of this offering, (3) the reclassification of our preferred stock warrant liability to additional paid in capital, a component of stockholders’ (deficit) equity, and (4) the filing of our restated certificate of incorporation upon the closing of this offering; and

 

   

on a pro forma as adjusted basis to give further effect to our issuance and sale of 4,700,000 shares of common stock in this offering at an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us.

Our capitalization following the closing of this offering will be adjusted based on the actual initial public offering price and other terms of this offering determined at pricing. You should read this information in conjunction with our consolidated financial statements and the related notes appearing at the end of this prospectus and the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” section and other financial information contained in this prospectus.

 

     As of June 30, 2013  
     Actual     Pro
Forma
    Pro Forma
As Adjusted
 
    

(in thousands)

 

Cash and cash equivalents

   $ 21,309      $ 21,309      $ 83,999   
  

 

 

   

 

 

   

 

 

 

Long-term debt

   $ 4,208      $ 4,208      $ 4,208   

Preferred stock warrant liability

     657        —          —     

Redeemable convertible preferred stock (Series A, B, C, C-1, D and BRN), par value $0.0001 per share; 28,235,917 shares authorized, 22,893,811 shares issued and outstanding, actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted

     99,317        —          —     

Preferred stock, par value $0.0001 per share; no shares authorized, issued or outstanding, actual; 10,000,000 shares authorized and no shares issued or outstanding, pro forma and pro forma as adjusted

     —          —          —     

Common stock, par value $0.0001 per share; 43,500,000 shares authorized, 2,339,237 shares issued and 2,231,560 outstanding, actual; 200,000,000 shares authorized, pro forma and pro forma as adjusted; 11,077,322 shares issued and 10,969,645 outstanding, pro forma; 15,777,322 shares issued and 15,669,645 outstanding, pro forma as adjusted

     1        2        2   

Loans due from stockholders(1)

     (662     (662     (662

Additional paid in capital

     —          73,249        135,684   

Accumulated deficit

     (89,286     (62,562     (62,562

Accumulated other comprehensive loss

     (395     (395     (395
  

 

 

   

 

 

   

 

 

 

Total stockholders’ (deficit) equity

     (90,342     9,632        72,067   
  

 

 

   

 

 

   

 

 

 

Total capitalization

   $ 13,840      $ 13,840      $ 76,275   
  

 

 

   

 

 

   

 

 

 

 

(1) These loans were repaid in August 2013.

 

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Each $1.00 increase (decrease) in the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the pro forma as adjusted amount of each of cash and cash equivalents, additional paid in capital, total stockholders’ (deficit) equity and total capitalization by approximately $4.4 million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us. Similarly, each increase (decrease) of 1.0 million shares in the number of shares offered by us at the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the pro forma as adjusted amount of each of cash and cash equivalents, additional paid in capital, total stockholders’ (deficit) equity and total capitalization by approximately $14.0 million.

The number of shares in the table above does not include:

 

   

95,419 shares of our common stock that were issued upon the automatic conversion in August 2013 of 250,000 shares of our Series BRN preferred stock issued in July 2013;

 

   

2,375,882 shares of our common stock issuable upon exercise of stock options outstanding as of June 30, 2013, at a weighted-average exercise price of $2.57 per share;

 

   

1,335,877 shares of our common stock reserved for future issuance under our 2013 Incentive Award Plan, which will become effective on the day prior to the public trading date of our common stock; and

 

   

74,413 shares of our common stock issuable upon exercise of warrants outstanding as of June 30, 2013, at a weighted-average exercise price of $11.32 per share.

 

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DILUTION

If you invest in our common stock in this offering, your ownership interest will be immediately diluted to the extent of the difference between the initial public offering price per share and the pro forma as adjusted net tangible book value per share of our common stock after this offering.

As of June 30, 2013, we had a historical net tangible book value (deficit) of $(89.7) million, or $(38.34) per share of common stock. Our historical net tangible book value per share represents total tangible assets (total assets less intangible assets) less total liabilities and redeemable convertible preferred stock, divided by the number of shares of our common stock outstanding as of June 30, 2013.

Our pro forma net tangible book value as of June 30, 2013 was $9.6 million, or $0.87 per share of our common stock. Pro forma net tangible book value per share represents total tangible assets less total liabilities, divided by the number of shares of our common stock outstanding as of June 30, 2013, after giving effect to (1) the automatic conversion of 583,333 shares of our Series BRN preferred stock into 222,646 shares of our common stock, which occurred in August 2013 upon the initial filing of the registration statement of which this prospectus is a part, (2) the automatic conversion of all outstanding shares of our preferred stock into common stock immediately prior to the closing of this offering and (3) the reclassification of our preferred stock warrant liability to additional paid in capital, a component of stockholders’ (deficit) equity.

After giving further effect to the sale of 4,700,000 shares of common stock in this offering at an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, our pro forma as adjusted net tangible book value as of June 30, 2013 would have been approximately $72.1 million, or approximately $4.57 per share. This amount represents an immediate increase in pro forma net tangible book value of $3.70 per share to our existing stockholders and an immediate dilution in pro forma net tangible book value of approximately $10.43 per share to new investors purchasing shares of common stock in this offering. We determine dilution by subtracting the pro forma as adjusted net tangible book value per share after this offering from the amount of cash that a new investor paid for a share of common stock. The following table illustrates this dilution:

 

Assumed initial public offering price per share

     $ 15.00   

Historical net tangible book value (deficit) per share as of June 30, 2013

   $ (38.34  

Pro forma net tangible book value per share as of June 30, 2013

     0.87     

Increase per share attributable to this offering

     3.70     
  

 

 

   

Pro forma as adjusted net tangible book value per share after this offering

     $ 4.57   
    

 

 

 

Dilution per share to new investors in this offering

     $ 10.43   
    

 

 

 

Each $1.00 increase (decrease) in the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, would increase (decrease) the pro forma as adjusted net tangible book value per share after this offering by approximately $0.28, and dilution in pro forma as adjusted net tangible book value per share to new investors by approximately $0.72, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us. Each increase of 1.0 million shares in the number of shares offered by us would increase our pro forma as adjusted net tangible book value per share after this offering by approximately $0.56 per share and decrease the dilution to new investors by approximately $0.56 per share, assuming that the assumed initial public offering price remains the same, and after deducting the estimated underwriting discounts and commissions and the estimated offering expenses payable by us. Each decrease of 1.0 million shares in the number of shares offered by us would decrease our pro forma as adjusted net tangible book value per share after this offering by

 

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approximately $0.63 per share and increase the dilution to new investors by approximately $0.63 per share, assuming that the assumed initial public offering price remains the same, and after deducting the estimated underwriting discounts and commissions and the estimated offering expenses payable by us.

If the underwriters exercise their option to purchase additional shares of our common stock in full in this offering, the pro forma as adjusted net tangible book value after this offering would be $4.97 per share, the increase in pro forma net tangible book value per share to existing stockholders would be $4.10 and the dilution per share to new investors would be $10.03 per share, in each case assuming an initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus.

The following table summarizes on the pro forma as adjusted basis described above, as of June 30, 2013, the differences between the number of shares purchased from us, the total consideration paid to us in cash and the average price per share that existing stockholders and new investors paid. The calculation below is based on an assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, before deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us.

 

     Shares Purchased     Total Consideration     Average Price
Per  Share
 
     Number      Percent     Amount      Percent    

Existing stockholders

     11,077,322         70.2   $ 84,941,319         54.6   $ 7.67   

New investors

     4,700,000         29.8        70,500,000         45.4        15.00   
  

 

 

    

 

 

   

 

 

    

 

 

   

Total

     15,777,322         100   $ 155,441,319         100  
  

 

 

    

 

 

   

 

 

    

 

 

   

The foregoing tables and calculations are based on 2,339,237 shares of our common stock outstanding as of June 30, 2013, 222,646 shares of our common stock issued in August 2013 upon the automatic conversion of our Series BRN preferred stock outstanding as of June 30, 2013 and 8,515,439 shares of our common stock issuable upon the automatic conversion of all outstanding shares of our preferred stock immediately prior to the closing of this offering, and exclude:

 

   

95,419 shares of our common stock that were issued upon the automatic conversion in August 2013 of 250,000 shares of our Series BRN preferred stock issued in July 2013;

 

   

2,375,882 shares of our common stock issuable upon exercise of stock options outstanding as of June 30, 2013, at a weighted-average exercise price of $2.57 per share;

 

   

1,335,877 shares of our common stock reserved for future issuance under our 2013 Incentive Award Plan; and

 

   

74,413 shares of our common stock issuable upon exercise of warrants outstanding as of June 30, 2013, at a weighted-average exercise price of $11.32 per share.

To the extent any of these outstanding options or warrants is exercised, there will be further dilution to new investors. If all of such outstanding options and warrants had been exercised as of June 30, 2013, the pro forma as adjusted net tangible book value per share after this offering would be $4.35, and total dilution per share to new investors would be $10.65.

If the underwriters exercise their option to purchase additional shares of our common stock in full:

 

   

the percentage of shares of common stock held by existing stockholders will decrease to approximately 67.2% of the total number of shares of our common stock outstanding after this offering; and

 

   

the number of shares held by new investors will increase to 5,405,000, or approximately 32.8% of the total number of shares of our common stock outstanding after this offering.

 

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Certain affiliates of our directors and other principal stockholders have indicated an interest in purchasing an aggregate of approximately $14.7 million in shares of our common stock in this offering at the initial public offering price. However, because indications of interest are not binding agreements or commitments to purchase, the underwriters may determine to sell more, less or no shares in this offering to any of these stockholders, or any of these stockholders may determine to purchase more, less or no shares in this offering. The foregoing discussion and tables do not reflect any potential purchases by these stockholders.

 

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SELECTED CONSOLIDATED FINANCIAL DATA

The following tables set forth, for the periods and as of the dates indicated, our selected consolidated financial data. The consolidated statements of operations data for the years ended December 31, 2011 and 2012 and the consolidated balance sheet data as of December 31, 2011 and 2012 are derived from our audited consolidated financial statements included elsewhere in this prospectus. The consolidated statements of operations data for the six months ended June 30, 2012 and 2013 and the consolidated balance sheet data as of June 30, 2013 are derived from our unaudited consolidated financial statements included elsewhere in this prospectus. The unaudited consolidated financial statements include, in the opinion of management, all adjustments consisting of only normal recurring adjustments, that management considers necessary for the fair presentation of the financial information set forth in those statements. You should read the following information together with the more detailed information contained in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the related notes included elsewhere in this prospectus. Our historical results are not indicative of the results to be expected in the future and results of interim periods are not necessarily indicative of results for the entire year.

 

     Years Ended December 31,     Six Months Ended
June 30,
 
     2011     2012     2012     2013  
     (in thousands, except share and per share data)  

Consolidated Statements of Operations:

        

Revenue

   $ 905      $ 1,047      $ 434      $ 4,265   
  

 

 

   

 

 

   

 

 

   

 

 

 

Operating expenses:

        

Research and development

     11,440        13,052        6,228        11,617   

General and administrative

     4,787        6,625        2,830        4,416   
  

 

 

   

 

 

   

 

 

   

 

 

 

Total operating expenses

     16,227        19,677        9,058        16,033   
  

 

 

   

 

 

   

 

 

   

 

 

 

Loss from operations

     (15,322     (18,630     (8,624     (11,768

Other income (expense):

        

Interest income

     37        69        15        88   

Interest expense

     (1,708     (710     (396     (590

Change in fair value of preferred stock warrant liability

     (269     340        13        (85

Foreign currency transaction gain (loss)

     407        (309     56        147   
  

 

 

   

 

 

   

 

 

   

 

 

 

Net loss

     (16,855     (19,240     (8,936     (12,208

Accretion of redeemable convertible preferred stock

     (2,967     (4,967     (2,485     (2,749
  

 

 

   

 

 

   

 

 

   

 

 

 

Net loss attributable to common stockholders

   $ (19,822   $ (24,207   $ (11,421   $ (14,957
  

 

 

   

 

 

   

 

 

   

 

 

 

Net loss per share attributable to common stockholders:

        

Basic and diluted(1)

   $ (10.50   $ (11.70   $ (5.63   $ (6.83

Weighted average common shares outstanding:

        

Basic and diluted(1)

     1,887,082        2,069,071        2,027,221        2,190,479   

Pro forma net loss per share attributable to common stockholders (unaudited):

        

Basic and diluted(1)

     $ (1.98     $ (1.12

Pro forma weighted average common shares outstanding (unaudited):

        

Basic and diluted(1)

       9,700,591          10,928,564   

 

(1) See Note 2 to our notes to consolidated financial statements included elsewhere in this prospectus for an explanation of the method used to calculate the historical and pro forma basic and diluted net loss per common share and the number of shares used in the computation of the per share amounts.

 

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     As of December 31,     As of June  30,
2013
 
     2011     2012    
     (in thousands)  

Consolidated Balance Sheet Data:

      

Cash and cash equivalents

   $ 22,440      $ 4,886      $ 21,309   

Working capital

     22,263        613        11,818   

Total assets

     30,048        12,670        31,377   

Long-term debt

     3,166        1,256        4,208   

Preferred stock warrant liability

     744        404        657   

Redeemable convertible preferred stock

     74,319        79,286        99,317   

Additional paid in capital

     —          —          —     

Accumulated deficit

     (51,695     (75,205     (89,286

Total stockholders’ deficit

     (52,882     (75,923     (90,342

 

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MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes thereto included elsewhere in this prospectus. Some of the information contained in this discussion and analysis or set forth elsewhere in this prospectus, including information with respect to our plans and strategy for our business and related financing, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this prospectus, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a clinical-stage nanomedicine platform company developing Accurins, our novel targeted and programmable therapeutics. Accurins are designed with specified physical and chemical characteristics to target specific cells or tissues and concentrate a therapeutic payload at the site of disease to enhance efficacy while minimizing adverse effects on healthy tissues. Our strategy is to leverage our medicinal nanoengineering platform to develop our own pipeline of Accurins, initially in oncology, as well as Accurins in collaboration with biopharmaceutical companies. Our lead drug candidate, BIND-014, is in Phase 2 clinical trials for non-small cell lung cancer, or NSCLC, and metastatic castrate-resistant prostate cancer, or mCRPC. To date in 2013, we have announced collaborations with Amgen, Pfizer and AstraZeneca to develop Accurins based on therapeutic payloads from their product pipelines, with the potential to achieve a total of over $1 billion in upfront and future milestone payments, including over $450 million in pre-commercial milestones.

We design, manage and evaluate the results of all of our research and development plans centrally and have engaged a network of clinical trial sites and clinical research organizations, or CROs, to execute on specific phases of our research and development programs. By employing this network of CROs, we seek to manage multiple development programs while maintaining flexibility in our cost structure.

We were incorporated in May 2006 and commenced active operations in early 2007. Our operations to date have been limited to organizing and staffing our company, business planning, raising capital, developing our technology, identifying potential drug candidates, undertaking preclinical studies and, beginning in 2011, conducting clinical trials. To date, we have financed our operations primarily through private placements of our preferred stock and convertible debt securities, funding received from collaboration and license agreements, government grants and our credit facility. We have no products approved for sale and all of our revenue to date has been collaboration revenue or government grant revenue. Since our inception and through June 30, 2013, we have raised an aggregate of $113.8 million to fund our operations, of which $14.8 million was through our collaborations and license agreements, $84.9 million was from the sale of preferred stock and convertible debt securities, $4.8 million was from government grants and $9.3 million was from borrowings under our credit facility as well as capital leases. As of June 30, 2013, our cash and cash equivalents were $21.3 million, of which $2.8 million was held by our Russian subsidiary designated solely for use in its operations. As of June 30, 2013, we also had $1.4 million in restricted cash held in our Russian subsidiary. In addition, in July 2013 we issued and sold 250,000 shares of Series BRN preferred stock to an existing investor for $1.5 million in gross proceeds, which shares were automatically converted into 95,419 shares of our common stock in August 2013.

Since inception, we have incurred significant operating losses. Our net loss was $16.9 million for the year ended December 31, 2011, $19.2 million for the year ended December 31, 2012 and $12.2 million for the six months ended June 30, 2013 compared to $8.9 million for the six months ended June 30, 2012. As of June 30, 2013, we had an accumulated deficit of $89.3 million. We expect to continue to incur significant expenses and operating losses for the foreseeable future. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase substantially as we:

 

   

conduct the Phase 2 clinical trials of BIND-014 and potentially conduct pivotal clinical trials of BIND-014;

 

   

continue the research and development of our other drug candidates, including potentially in-licensing other technologies and compounds, seek to enhance our medicinal nanoengineering platform and discover and develop additional drug candidates;

 

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seek regulatory approvals for any drug candidates that successfully complete clinical trials, potentially establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;

 

   

maintain, expand and protect our intellectual property portfolio; and

 

   

add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and license and collaboration agreements with partners. We may be unable to raise capital when needed or on attractive terms, which would force us to delay, limit, reduce or terminate our product development or future commercialization efforts. We will need to generate significant revenues to achieve profitability, and we may never do so.

The consolidated financial statements and following information include the accounts of BIND Therapeutics, Inc. and our wholly owned subsidiaries, BIND RUS, LLC, a Russian limited liability corporation, and BIND Securities Corporation, a Massachusetts securities corporation. All intercompany accounts and transactions have been eliminated.

Collaborations

In addition to our internal development programs, we actively seek opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. We have established a number of collaborations with industry leaders, including announced agreements with Amgen, Inc., Pfizer Inc. and AstraZeneca AB to develop Accurins based on therapeutic payloads from their product pipelines. Our collaboration agreements generally require the collaborator to pay all the development costs associated with the Accurin, including those incurred by us. In addition, the upfront and potential milestone payments received under these agreements provide us with additional capital resources to develop our own proprietary pipeline of Accurins. Aggregate upfront and contingent clinical, regulatory and marketing milestone payments under these agreements are over $1 billion, exclusive of potential royalties. Over $450 million of these potential milestones are pre-commercial, of which approximately $11 million are pre-IND, approximately $190 million are clinical development and approximately $250 million are regulatory milestones. We expect that at least one of our collaborations will advance an Accurin into the clinic by the end of 2014.

Amgen

In January 2013, we entered into a license agreement with Amgen, pursuant to which we granted to Amgen an option to obtain an exclusive worldwide license to develop, manufacture and commercialize an Accurin incorporating a specified Amgen kinase inhibitor for all uses except for some vaccine applications. Amgen may exercise its option during a period of approximately 12 months, beginning on the effective date of the agreement, by paying us a specified option exercise fee. If Amgen fails to exercise its option within such time period, then we have the right to exercise an exclusive option to obtain a license from Amgen to develop, manufacture and commercialize Accurins containing the Amgen kinase inhibitor upon terms to be mutually agreed. Under the agreement, we received an upfront payment of $5.0 million and have the potential to receive contingent payments for up to two indications totaling up to $111.5 million in the aggregate upon exercise of the option and achievement by Amgen of specified development and regulatory events with respect to such indications, plus additional contingent payments totaling up to $188 million in the aggregate upon the achievement by Amgen of specified commercial events with respect to such indications. If Amgen exercises its option, Amgen will reimburse us for all external expenses we incur relating to the agreement after such exercise. We will also receive tiered royalties in the mid-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed products. Amgen is also obligated to pay certain development costs during the research period. We are

 

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responsible for manufacturing licensed compounds for use in preclinical studies, and we will collaborate with Amgen in developing and implementing a strategy for subsequent manufacturing.

Pfizer

In March 2013, we entered into a research, option and license agreement with Pfizer, pursuant to which we granted to Pfizer two options to obtain an exclusive worldwide license to use, develop, manufacture and commercialize Accurins incorporating specified Pfizer drug candidates, for the treatment, prevention and/or diagnosis of any disease or medical condition in humans, except that the licensed rights exclude some vaccine products and products for the treatment of brain cancer. Pfizer may exercise either one or both of its options to acquire the exclusive license for the specified drug candidate during a period of approximately 30 months, beginning on the effective date of the agreement and subject to certain adjustments, by paying us a specified option exercise fee. Pfizer is required to pay for all of our development costs. We are responsible for manufacturing licensed compounds through early clinical trials. Under the agreement, we received an upfront payment of $4.0 million and have the potential to receive contingent payments totaling up to $89.5 million in the aggregate under each option upon exercise of the option and achievement by Pfizer of specified development and regulatory events, plus additional contingent payments totaling up to $110 million in the aggregate under each option upon achievement by Pfizer of specified commercial events. We will also receive royalties in the low-single digit to the high-single digit percentages of aggregate worldwide net sales of each licensed product.

AstraZeneca

In April 2013, we entered into a license agreement with AstraZeneca, pursuant to which we granted to AstraZeneca a worldwide license to research, develop, manufacture and commercialize Accurins incorporating a specified AstraZeneca product candidate for any therapeutic use in humans or animals. AstraZeneca is required to pay for all of our development costs. We are responsible for manufacturing licensed product for use in preclinical and some clinical trials. Under the agreement, we received an upfront payment of $4.0 million and have the potential to receive contingent payments totaling up to $193 million in the aggregate upon achievement by AstraZeneca of specified clinical, regulatory and commercial events. We will also receive tiered royalties in the low-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed product.

Financial Overview

Revenue

Our revenue consists of collaboration revenue, which may include amounts recognized related to upfront payments for licenses or options to obtain licenses in the future, research and development funding and milestone payments earned under collaboration and license agreements with our collaboration partners. In addition, we collect revenue under the terms of government contracts which require the performance of certain research and development activities. We expect that any revenue we generate will fluctuate from quarter to quarter as a result of the timing and amount of license fees, research and development reimbursements, payments for manufacturing services, milestone and other payments from collaborations. We do not expect to generate revenue from product sales for at least the next several years. If we or our collaborators fail to complete the development of our drug candidates in a timely manner or obtain regulatory approval for them, our ability to generate future revenue, and our results of operations and financial position, would be materially adversely affected.

Research and Development

Research and development expenses consist of expenses incurred in performing research and development activities, including compensation and benefits for full-time research and development employees, an allocation of facilities expenses, overhead expenses, manufacturing process-development and scale-up activities, clinical

 

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trial and related clinical manufacturing expenses, fees paid to CROs and investigative sites, payments to universities under our license agreements and other outside expenses. In the early phases of development, our research and development costs are often devoted to expanding our product platform and are not necessarily allocable to a specific target.

Our research and development costs are made up of external costs, which since the first quarter of 2010 we track on a program-by-program basis and internal research and development costs which are primarily compensation expenses for our full-time research and development employees and related expenses. As we expand the clinical development of BIND-014, the amount of research and development spending allocated to external versus internal spending will continue to grow, while our internal spending should grow at a slower and more controlled pace. Beginning in January 2013, we implemented a project-based time reporting system so that we can allocate internal spending on a project-by-project basis. We have incurred a total of $61.4 million in research and development expenses from inception through June 30, 2013, with a majority of the expenses being spent on the development of BIND-014 and the remainder being spent on the development of our medicinal nanoengineering platform and our early stage programs.

We expense research and development costs as incurred. Conducting a significant amount of research and development is central to our business model. Drug candidates in late stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of late stage clinical trials. We plan to increase our research and development expenses for the foreseeable future as we seek to complete development of BIND-014, and to further advance our preclinical and earlier stage research and development projects. The successful development of our clinical and preclinical drug candidates is highly uncertain. At this time, we cannot reasonably estimate the nature, timing or costs of the efforts that will be necessary to complete the remainder of the development of BIND-014 or any of our preclinical programs or the period, if any, in which material net cash inflows from these drug candidates may commence. Clinical development timelines, the probability of success and development costs can differ materially from expectations. For example, if the FDA or another regulatory authority were to require us to conduct clinical trials beyond those which we currently anticipate will be required for the completion of clinical development of a drug candidate or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development.

General and Administrative

General and administrative expenses consist primarily of salaries and related benefits, including stock-based compensation, related to our executive, finance, business development and support functions. Other general and administrative expenses include facility-related costs not otherwise allocated to research and development expenses, travel expenses for our general and administrative personnel and professional fees for auditing, tax and corporate legal services, including intellectual property related legal services. We anticipate that our general and administrative expenses will increase in future periods, reflecting an expanding infrastructure and increased professional fees associated with being a public reporting company.

Interest Income

Interest income consists of interest income earned on our cash and cash equivalents and interest income from loans to our founders and chief executive officer.

Interest Expense

Interest expense consists of interest expense on our amounts borrowed under credit facility, capital leases, and convertible notes.

 

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Change in Fair Value of Preferred Stock Warrant Liability

The preferred stock warrant liability is associated with warrants to purchase preferred stock issued to lenders under our debt facilities. The change in fair value consists of the calculated change in value based upon the fair value of the underlying security at the end of each reporting period as calculated using the Black-Scholes option-pricing model.

Foreign Currency Transaction Gain (Loss)

The functional currency of our Russian subsidiary is the ruble. All assets and liabilities of the subsidiary are translated at year-end exchange rates and revenues and expenses are translated at average exchange rates for the year. Translation adjustments are reflected in the accumulated other comprehensive (loss) income component of stockholders’ equity. At December 31, 2011 and 2012 and June 30, 2013, we maintained cash, including restricted cash of $7.4 million, $3.7 million and $4.2 million, respectively, in Russian banks, a majority of which is denominated in U.S. dollars. Accordingly, the amounts denominated in U.S. dollars are subject to transaction gains and losses, which are reported in the accompanying consolidated statement of operations.

Critical Accounting Policies and Use of Estimates

Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States, or GAAP. The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported revenues and expenses during the reporting periods. These items are monitored and analyzed by us for changes in facts and circumstances, and material changes in these estimates could occur in the future. We base our estimates on historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Changes in estimates are reflected in reported results for the period in which they become known. Actual results may differ materially from these estimates under different assumptions or conditions.

While our significant accounting policies are more fully described in the notes to our consolidated financial statements included elsewhere in this prospectus, we believe that the following accounting policies are critical to the process of making significant judgments and estimates in the preparation of our consolidated financial statements and understanding and evaluating our reported financial results.

Revenue Recognition

Collaborative Research and Development and Multiple-Deliverable Arrangements

We enter into collaborative arrangements for the development and commercialization of drug candidates utilizing our technology. The terms of these agreements have typically included multiple deliverables by us (for example, license rights, research and development services and manufacturing of clinical materials) in exchange for consideration to us of some combination of non-refundable license fees, research and development funding, payments based upon achievement of clinical development or other milestones and royalties in the form of a designated percentage of product sales or profits.

Revenue is recognized when there is persuasive evidence that an arrangement exists, delivery has occurred, the price is fixed and determinable and collection is reasonably assured. Multiple-deliverable arrangements, such as license and development agreements, are analyzed to determine whether the deliverables can be separated or whether they must be accounted for as a single unit of accounting. When deliverables are separable, consideration received is allocated to the separate units of accounting based on the relative selling price method

 

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and the appropriate revenue recognition principles are applied to each unit. When we determine that an arrangement should be accounted for as a single unit of accounting, we must determine the period over which the performance obligations will be performed and revenue will be recognized.

The assessment of multiple-deliverable arrangements requires judgment in order to determine the appropriate unit of accounting, the estimated selling price of each unit of accounting and the point in time that, or period over which, revenue should be recognized.

Deferred Revenue

Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying consolidated balance sheets. Amounts not expected to be recognized within one year following the balance sheet date are classified as non-current deferred revenue.

Accrued Expenses

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

 

   

fees payable to CROs and investigative sites in connection with clinical studies;

 

   

fees payable to vendors in connection with preclinical development activities; and

 

   

fees payable to vendors related to product manufacturing, development and distribution of clinical supplies.

We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple research institutions and CROs that conduct and manage clinical studies on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract, and may result in uneven payment flows and expense recognition. Payments under some of these contracts depend on factors such as the successful enrollment of patients and the completion of clinical trial milestones. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual accordingly. Our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in our reporting changes in estimates in any particular period. We have not experienced any significant adjustments to our estimates to date.

Stock-Based Compensation

We issue stock-based awards to employees and non-employees, generally in the form of stock options and restricted stock. We account for our stock-based awards in accordance with FASB ASC Topic 718, Compensation—Stock Compensation, or ASC 718. ASC 718 requires all stock-based payments to employees, including grants of employee stock options and modifications to existing stock options, to be recognized in the consolidated statements of operations and comprehensive loss based on their fair values. We account for stock-based awards to non-employees in accordance with FASB ASC Topic 505-50, Equity-Based Payments to Non-Employees, which requires the fair value of the award to be re-measured at fair value as the award vests. We

 

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recognize the compensation cost of stock-based awards on a straight-line basis over the vesting period of the award for employees and non-employees. We have issued some performance based grants where the vesting of the grant is tied to certain milestone performance and in these cases, the compensation is recognized as an expense when the probability of the milestone is met (and stock vested). Compensation expense related to our stock based awards is subject to a number of estimates including the estimated volatility and underlying fair value of our common stock as well as the estimated life of the awards. For a detailed description of how we estimate fair value for purposes of option grants and the methodology used in measuring stock-based compensation expense, see “Stock-Based Compensation and Common Stock Valuation” below. Following the consummation of this offering, stock option and restricted stock values will be determined based on the market price of our common stock.

Results of Operations for the Six Months Ended June 30, 2012 and 2013

Revenue

The following is a comparison of revenue for the six months ended June 30, 2012 and 2013 (in thousands, except percentages):

 

     Six Months
Ended June 30,
     Increase  
     2012      2013     

Grant revenue

   $ 90       $ 365       $ 275         306

Collaboration revenue

     344         3,900         3,556         1,034
  

 

 

    

 

 

    

 

 

    

Total revenue

   $ 434       $ 4,265       $ 3,831         882
  

 

 

    

 

 

    

 

 

    

During the six months ended June 30, 2013, total revenue increased by $3.8 million, or 882% compared to the same period in 2012. Substantially all of the increase is related to the recognition of a portion of the upfront payments we received upon entering into collaboration agreements with Amgen, Pfizer and AstraZeneca during 2013. In addition, during the six months ended June 30, 2013 we recognized a total of $0.4 million under the terms of our grant with the Russian Ministry of Industry and Trade.

Research and Development

The following is a comparison of research and development expenses for the six months ended June 30, 2012 and 2013 (in thousands, except percentages):

 

     Six Months Ended
June 30,
     Increase  
     2012      2013     

Research and development

   $ 6,228       $ 11,617       $ 5,389         87

During the six months ended June 30, 2013, our research and development expenses increased by $5.4 million, or 87% compared to the same period in 2012. The increase in research and development expenses was primarily driven by increases in our external research and development costs. Our external research and development expenses increased due to the increase in the number of patients in the Phase 1 clinical trial, the start-up costs for the Phase 2 clinical trials of BIND-014 and the further development of the manufacturing process for BIND-014.

Our internal research and development expenses also increased for the six months ended June 30, 2013 as compared to the same period in 2012 as a result of one-time payments due to the Massachusetts Institute of

 

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Technology, or MIT, under our license agreement resulting from the upfront payments we received upon entering into collaboration agreements with Amgen and Pfizer. In addition, increases in internal research and development expenses were driven by headcount increases in our U.S. and Russian operations and associated stock compensation expense compared to the same period in 2012. Staffing increases in the United States were driven primarily by the work associated with our collaborations with Amgen, Pfizer and AstraZeneca. Lastly, facilities costs increased as compared to the same period in 2012 as we moved from our previous location to our current facility in Cambridge in April 2012.

The following table illustrates the components of our research and development expenses during the periods indicated (in thousands, except percentages):

 

     Six Months Ended
June  30,
     Increase  
     2012        2013     

External research and development expenses:

               

BIND-014

   $ 1,257         $ 4,350       $ 3,093           246

Collaborations

     —             39         39           —     

Discovery and preclinical stage product programs, collectively

     118           179         61           52

Internal research and development expenses

     4,853           7,049         2,196           45
  

 

 

      

 

 

    

 

 

      

Total research and development expenses

   $ 6,228         $ 11,617       $ 5,389           87
  

 

 

      

 

 

    

 

 

      

General and Administrative

The following is a comparison of general and administrative expenses for the six months ended June 30, 2012 and 2013 (in thousands, except percentages):

 

     Six Months Ended
June  30,
     Increase  
     2012        2013     

General and administrative

   $ 2,830         $ 4,416       $ 1,586         56

For the six months ended June 30, 2013, our general and administrative expenses increased by $1.6 million, or 56% compared to the same period in 2012. The increase in our general and administrative expenses was driven by significant increases in professional fees in 2013 as a result of the legal costs associated with our collaboration agreements with Amgen, Pfizer and AstraZeneca and costs incurred in connection with a market research study, and significant increases in compensation expenses as we increased our general and administrative headcount to ten as of June 30, 2013 as compared to five as of June 30, 2012. In addition, there were increases in bank fees associated with the credit facility that we amended and restated in June 2013.

Change in Fair Value of Preferred Stock Warrant Liability

We recorded $0.1 million of expense for the six months ended June 30, 2013 for the increase in the fair market value of the underlying security, which was based upon the valuation performed as of June 30, 2013 (see “Stock-Based Compensation and Common Stock Valuation” below). The change in the preferred stock warrant liability for the six months ended June 30, 2012 was not material.

Foreign Currency Transaction Gains

Because our Russian subsidiary’s functional currency is the ruble and the majority of its cash is held in U.S. dollars, the balances are subject to transaction gains and losses. We recorded approximately $147,000 and $56,000 of gains for the six months ended June 30, 2013 and 2012, respectively.

 

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Results of Operations for the Years Ended December 31, 2011 and 2012

Revenue

The following is a comparison of revenue for the years ended December 31, 2011 and 2012 (in thousands, except percentages):

 

     Years Ended
December  31,
     Increase  
     2011        2012     

Grant revenue

   $ 357         $ 479       $ 122           34

Collaboration revenue

     548           568         20           4
  

 

 

      

 

 

    

 

 

      

Total revenue

   $ 905         $ 1,047       $ 142           16
  

 

 

      

 

 

    

 

 

      

During the year ended December 31, 2012, total revenue increased by $0.1 million, or 16%, compared to the prior year, primarily due to the receipt of the revenue associated with the first stage of a grant from the Russian Ministry for Industry and Trade of the Russian Federation which was awarded in the third quarter of 2012.

Research and Development

The following is a comparison of research and development expenses for the years ended December 31, 2011 and 2012 (in thousands, except percentages):

 

     Years Ended December 31,      Increase  
     2011        2012     

Research and development

   $ 11,440         $ 13,052       $ 1,612         14

During the year ended December 31, 2012, our total research and development expenses increased by $1.6 million, or 14%, compared to the prior year, primarily due to costs associated with building out our research and development team in Russia. External research and development spending focused on the advancement of BIND-014, with expenses increasing for the year ended December 31, 2012 as compared to the prior year principally due to an increase in the number of patients enrolled in our Phase 1 clinical trial as well as the related costs associated with initiating work on a Phase 2 clinical trial for BIND-014. Our internal research and development expenses increased in 2012 as compared to 2011 primarily due to the increase in headcount in Russia and other headcount related costs including annual bonus and salary adjustments, as well as the increased facilities costs relating to our move from our previous location to our new facility in April 2012.

The following table illustrates the components of our research and development expenses during the periods indicated (in thousands, except percentages):

 

    Years Ended December 31,     Increase (Decrease)  
        2011             2012        

External research and development expenses:

        

BIND-014

  $ 2,846      $ 3,201      $ 355         12

Government grant activity

    242        50        (192      (79 %) 

Discovery and preclinical stage product programs, collectively

    62        155        93         150

Internal research and development expenses

    8,290        9,646        1,356         16
 

 

 

   

 

 

   

 

 

    

Total research and development expenses

  $ 11,440      $ 13,052      $ 1,612         14
 

 

 

   

 

 

   

 

 

    

 

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General and Administrative

The following is a comparison of general and administrative expenses for the years ended December 31, 2011 and 2012 (in thousands, except percentages):

 

     Years Ended December 31,      Increase  
     2011        2012     

General and administrative

   $ 4,787         $ 6,625       $ 1,838         38

For the year ended December 31, 2012, our general and administrative expenses increased by $1.8 million, or 38%, primarily related to increased compensation expenses as we grew from five general and administrative employees as of December 31, 2011 to eight general and administrative employees as of December 31, 2012, and increased legal, recruiting, stock-based compensation expense related to executives and facilities costs not allocated to research and development as we moved from our previous location to new facility in April 2012.

Interest Expense

The decrease in interest expense to $0.7 million for the year ended December 31, 2012 from $1.7 million for the year ended December 31, 2011 reflects the conversion of outstanding convertible notes into shares of our Series D preferred stock in November 2011.

Change in Fair Value of Preferred Stock Warrant Liability

We recorded $0.3 million of expense for the year ended December 31, 2011 reflecting the increase in the fair market value of the underlying security which was defined to be equal to the value paid by investors for the Series D preferred stock financing as compared to the original strike price of the warrant. We recorded a reduction of expense of $0.3 million for the year ended December 31, 2012 reflecting a decrease in the fair market value of the underlying security based upon the retrospective valuation performed as of September 1, 2012 (see “Stock-Based Compensation and Common Stock Valuation” below).

Foreign Currency Transaction Gains

Because our Russian subsidiary’s functional currency is the ruble and the majority of its cash is held in U.S. dollars, the balances are subject to transaction gains and losses. We recorded $0.4 million of gains for the year ended December 31, 2011 and $0.3 million of losses for the year ended December 31, 2012.

Liquidity and Capital Resources

Since our inception and through June 30, 2013, we have raised an aggregate of $113.8 million to fund our operations, of which $14.8 million was through our collaborations and license agreements, $84.9 million was from the sale of preferred stock and convertible debt securities, $4.8 million was from government grants and $9.3 million was from borrowings under our credit facility as well as capital leases.

As of June 30, 2013, our cash and cash equivalents were $21.3 million, of which $2.8 million was held by our Russian subsidiary designated solely for use in its operations, and is consolidated for financial reporting purposes. As of June 30, 2013, we also have $1.4 million in restricted cash held in our Russian subsidiary. In addition to our existing cash and cash equivalents, we receive research and development funding and are eligible to earn a significant amount of milestone payments under our collaboration agreements. Our ability to earn these milestone payments and the timing of achieving these milestones is dependent upon the outcome of our research and development and regulatory activities and is uncertain at this time. Our rights to receive research and development funding and the payment of certain milestones under our collaboration agreements are our only committed external source of funds. We also have $4.0 million available under our amended and restated credit facility described below.

 

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Indebtedness

In June 2013, we entered into an amended and restated credit facility with Hercules as lender. The credit facility provides funding for an aggregate principal amount of up to $8.5 million. The first advance was funded on the closing date of the credit facility in the aggregate principal amount of $4.5 million. The proceeds of the first advance were used to first repay in full all existing outstanding loans under our prior loan and security agreement with Hercules, in an aggregate principal amount of $2.3 million, and then for general corporate purposes. The credit facility amends and restates our prior loan and security agreement with Hercules, which was entered into in January 2011, and no amounts remain outstanding under that prior facility. Subject to customary conditions for funding and us delivering evidence that we have received proceeds or payments in an amount equal to at least $10.0 million, of which we received $8.7 million from the sale of our Series D preferred stock in June 2013 and $1.5 million from the sale of our Series BRN preferred stock in July 2013, the second advance of up to a principal amount of $4.0 million may be funded at our request before December 31, 2013, to be used for general corporate purposes. The credit facility is secured by substantially all of our personal property other than our intellectual property. The loans under the credit facility bear interest at an annual rate equal to (a) 10.25% plus (b) the prime rate (as reported in the Wall Street Journal) minus (c) 3.25% subject to a minimum of 10.25%. We are only required to make interest payments on any loans funded under the credit facility through February 28, 2014, or the interest-only period. The interest-only period automatically extends to June 2014 upon us receiving the proceeds or payments required to satisfy the conditions for funding of the second advance. All outstanding loans under the credit facility will begin amortizing at the end of the interest-only period, with monthly payments of principal and interest being made by us to Hercules in 30 consecutive monthly installments. All loans mature on the first day of the 30th month following the end of the interest-only period.

The credit facility includes affirmative and negative covenants applicable to us and our subsidiaries. The affirmative covenants include, among others, covenants requiring us (and us to cause our subsidiaries) to maintain our legal existence and governmental approvals, deliver certain financial reports and maintain insurance coverage. The negative covenants include, among others, restrictions on us and our subsidiaries transferring collateral, incurring additional indebtedness, engaging in mergers or acquisitions, paying dividends or making other distributions, making investments, creating liens, selling assets, and suffering a change in control, in each case subject to certain exceptions. Additionally, the credit facility restricts us from investing in our wholly-owned domestic subsidiary, BIND Biosciences Securities Corporation, unless we hold cash and other liquid investments equal to $25.0 million, less any payments of principal that we have made to Hercules under the credit facility.

The credit facility also includes events of default, the occurrence and continuation of which provide Hercules with the right to exercise remedies against us and the collateral securing the loans under the credit facility, including our cash. These events of default include, among other things, our failure to pay any amounts due under the credit facility, a breach of covenants under the credit facility, our insolvency and the insolvency of our subsidiaries, the occurrence of a material adverse effect, the occurrence of any default under certain other indebtedness, and a final judgment against us in an amount greater than $500,000.

Plan of Operations and Future Funding Requirements

Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party clinical research and development services, laboratory and related supplies, clinical costs, legal and other regulatory expenses and general overhead costs.

We expect that the net proceeds from this offering, together with our cash and cash equivalents as of June 30, 2013, borrowings available under our credit facility and research and development funding that we expect to receive under our existing collaborations, excluding any potential milestone payments, will fund our operating expenses and capital expenditure requirements through at least mid-2015, which we expect will enable us to complete our ongoing Phase 2 clinical trials of BIND-014 in NSCLC and mCRPC and, if such trials are successful, to initiate pivotal Phase 3 trials in these indications. We have based these estimates on assumptions

 

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that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Additionally, the process of testing drug candidates in clinical trials is costly, and the timing of progress in these trials is uncertain. Because our drug candidates are in various stages of clinical and preclinical development and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our drug candidates or whether, or when, we may achieve profitability. Our future capital requirements will depend on many factors, including:

 

   

our collaboration agreements remaining in effect and our ability to achieve milestones under these agreements;

 

   

the progress and results of our clinical trials of BIND-014;

 

   

the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other drug candidates;

 

   

the number and development requirements of other drug candidates that we pursue;

 

   

the costs, timing and outcome of regulatory review of our drug candidates;

 

   

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

 

   

the revenue, if any, received from commercial sales of our drug candidates for which we receive marketing approval;

 

   

the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and

 

   

the extent to which we acquire or in-license other products and technologies.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and revenue from license and collaboration arrangements. Except for any obligations of our collaborators to reimburse us for research and development expenses or to make milestone payments under our agreements with them and the second advance from our Hercules credit facility, upon completion of this offering, we will not have any committed external source of liquidity. To the extent that we raise additional capital through the future sale of equity or debt, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or drug candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market drug candidates that we would otherwise prefer to develop and market ourselves.

Cash Flows

The following is a summary of cash flows for the years ended December 31, 2011 and 2012 and the six months ended June 30, 2012 and 2013 (in thousands):

 

     Years Ended December 31,      Six Months Ended
June  30,
 
     2011     2012      2012      2013  

Net cash used in operating activities

   $ (13,025   $ (17,238    $ (9,410    $ (278

Net cash provided by (used in) investing activities

     4,464        1,311         1,842         (1,486

Net cash provided by (used in) financing activities

     29,025        (1,967      (1,013      18,431   

 

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Net Cash Used in Operating Activities

Net cash used in operating activities was $9.4 million during the six months ended June 30, 2012 compared to $0.3 million during the six months ended June 30, 2013. The decrease in cash used in operating activities in the first six months of 2013 was primarily driven by an increase in cash received from collaboration agreements compared to the first six months of 2012, offset by an increase in operating expenses compared to the first six months of 2012. There were no material collaboration agreements in 2012. Net cash used in operating activities was $13.0 million for the year ended December 31, 2011 compared to $17.2 million for the year ended December 31, 2012. The increase in cash used in operating activities was driven primarily by an increase in operating expenses in 2012 compared to 2011 related to increased clinical trial activity and start-up expenses of our Russian subsidiary.

Net Cash Provided by (Used in) Investing Activities

Net cash provided by investing activities was $1.8 million for the six months ended June 30, 2012 compared to net cash used of $1.5 million for the six months ended June 30, 2013. The decrease in the cash used in investing activities is due to a decrease in short-term investments maturing during the period combined with an increase in the purchase of fixed assets during the period. There were no purchases of short-term investments during the first six months of 2013. The increase of property and equipment purchases in the first six months of 2013 compared to 2012 consists primarily of purchases related to building out of our Russian laboratory.

Net cash provided by investing activities was $4.5 million for the year ended December 31, 2011 compared to $1.3 million for the year ended December 31, 2012. The decrease in cash provided by investing activities is primarily related to the decrease in short-term investments maturing during 2012 as compared to 2011. Additionally, a significant amount of net cash used in investing activities relates to the purchase of property and equipment, which occurred primarily in 2011, related to manufacturing equipment for the manufacture of our clinical product.

Net Cash Provided by (Used in) Financing Activities

Net cash provided by financing activities of $18.4 million during the six months ended June 30, 2013 is primarily due to cash received related to the sale of Series D preferred stock to investors for net proceeds of $17.2 million, as well as the net increase in debt of $1.2 million associated with the amended and restated credit facility. The net cash used in financing activities of $1.0 million during the six months ended June 30, 2012 is primarily due to payments on debt facilities within the period. Net cash provided by financing activities during the year ended December 31, 2011 was $29.0 million and is primarily related to the sale of Series D and Series BRN preferred stock, proceeds from convertible notes and borrowings under the credit facility, offset by repayments on the credit facility. In November 2011, we sold shares of Series D and Series BRN preferred stock to investors for net proceeds of $19.8 million. There was no sale of preferred stock in 2012 and the net cash used by financing activities was $2.0 million and is related mostly to the repayment of amounts outstanding under credit agreements entered into in the previous year.

Contractual Obligations and Contingent Liabilities

The following summarizes our significant contractual obligations as of June 30, 2013 (in thousands):

 

Contractual Obligations

   Total      Less than
1 Year
     1 to 3 Years      3 to 5 Years      More than
5 Years
 

Operating leases

   $ 5,990       $ 1,498       $ 3,133       $ 1,359       $   

Research and development contract obligations

     1,795         300         200         515         780   

Long term debt

     5,863         919         4,252         692           
  

 

 

    

 

 

    

 

 

    

 

 

    

 

 

 

Total obligations

   $ 13,648       $ 2,717       $ 7,585       $ 2,566       $ 780   
  

 

 

    

 

 

    

 

 

    

 

 

    

 

 

 

 

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Operating Leases. Represents future minimum lease payments under non-cancelable operating leases in effect as of June 30, 2013, including the remaining lease payments for our current facilities in Cambridge, Massachusetts. The minimum lease payments above do not include common area maintenance charges or real estate taxes.

Research and development contract obligations. Represents minimum annual license fees payable to universities under our license agreements.

Long term debt. Represents obligations by us to make payments under long-term equipment lease and loan agreements. These amounts include interest.

The contractual obligations table does not include any potential contingent payments upon the achievement by us specified patent prosecution, clinical, regulatory and commercial events, as applicable, or royalty payments we may be required to make under license agreements we have entered into with various universities pursuant to which we have in-licensed certain intellectual property, including our license agreement with the MIT. See “Business—Intellectual Property—In-Licensed Intellectual Property” for additional information. The table also excludes potential payments we may be required to make under manufacturing and CRO agreements as the timing of when these payments will actually be made is uncertain and the payments are contingent upon the initiation and completion of future activities.

Stock-Based Compensation and Common Stock Valuation

Stock-Based Compensation

We estimate the fair value of our stock-based awards to employees and non-employees using the Black-Scholes option-pricing model, which requires the input of highly subjective assumptions, including (a) the expected volatility of our stock, (b) the expected term of the award, (c) the risk-free interest rate, and (d) expected dividends. Due to the lack of a public market for the trading of our common stock and a lack of company-specific historical and implied volatility data, we have based our estimate of expected volatility on the historical volatility of a group of companies in the pharmaceutical and biotechnology industries in a similar stage of development as us and that are publicly traded. For these analyses, we have selected companies with comparable characteristics to ours including enterprise value, risk profiles and with historical share price information sufficient to meet the expected life of the stock-based awards. We compute the historical volatility data using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of our stock-based awards. We will continue to apply this process until a sufficient amount of historical information regarding the volatility of our own stock price becomes available. We have estimated the expected life of our employee stock options using the “simplified” method, whereby, the expected life equals the average of the vesting term and the original contractual term of the option. The risk-free interest rates for periods within the expected life of the option are based on the U.S. Treasury yield curve in effect during the period the options were granted.

We are also required to estimate forfeitures at the time of grant, and revise those estimates in subsequent periods if actual forfeitures differ from estimates. We use historical data to estimate pre-vesting option forfeitures and record stock-based compensation expense only for those awards that are expected to vest. To the extent that actual forfeitures differ from our estimates, the difference is recorded as a cumulative adjustment in the period the estimates were revised. Stock-based compensation expense recognized in the financial statements is based on awards that are ultimately expected to vest.

 

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We have computed the fair value of employee stock options at date of grant using the following weighted-average assumptions:

 

     Year Ended
December 31,
     Six Months Ended
June 30,
 
         2011              2012              2012              2013      
                   (unaudited)  

Expected volatility

     66%         66%         66%         66%   

Expected term (in years)

     7.00         7.04         5.96         6.0   

Risk-free interest rate

     2.69         1.15         1.05         1.03   

Expected dividend yield

     0.0%         0.0%         0.0%         0.0%   

Stock-based compensation for employees and non-employees were allocated as outlined below (in thousands):

 

     Years Ended
December 31,
     Six Months Ended
June 30,
 
         2011              2012              2012              2013      
                  

(unaudited)

 

Research and development

   $ 189       $ 469       $ 151       $ 625   

General and administrative

     54         224         60         251   
  

 

 

    

 

 

    

 

 

    

 

 

 

Total

   $ 243       $ 693       $ 211       $ 876   
  

 

 

    

 

 

    

 

 

    

 

 

 

As of June 30, 2013, we had $6.3 million of total unrecognized compensation expense, net of related forfeiture estimates, which is expected to be recognized over a weighted-average remaining vesting period of approximately 2.92 years. We expect the impact of our stock-based compensation expense for stock options and restricted stock granted to employees and non-employees to grow in future periods due to the potential increases in the value of our common stock and headcount.

Common Stock Valuation

We have historically granted stock options at exercise prices not less than the fair value of our common stock. As there has been no public market for our common stock to date, the estimated fair value of our common stock has been determined by our board of directors. We are a private company with no active public market for our common stock. Therefore, our board of directors has estimated per share fair value of our common stock at each grant date using contemporaneous valuations performed in accordance with the guidance outlined in the American Institute of Certified Public Accountants Practice Aid, Valuation of Privately-Held Company Equity Securities Issued as Compensation, also known as the Practice Aid. In conducting these valuations, our board of directors considered all objective and subjective factors that it believed to be relevant, including its and management’s best estimate of our business condition, prospects and operating performance at each grant date. In reaching these fair value determinations, our board of directors and management considered a range of objective and subjective factors and assumptions including, among others:

 

   

the prices of our preferred stock sold to or exchanged between investors in arm’s length transactions, and the rights, preferences and privileges of our preferred stock as compared to those of our common stock, including the liquidation preferences of our preferred stock;

 

   

our results of operations, financial position and the status of research and development efforts;

 

   

the composition of, and changes to, our management team and board of directors;

 

   

the lack of liquidity of our common stock as a private company;

 

   

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

 

   

the achievement of enterprise milestones, including entering into collaboration and license agreements;

 

   

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

 

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any external market conditions affecting the life sciences and biotechnology industry sectors;

 

   

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

 

   

any recent contemporaneous third-party valuations prepared in accordance with methodologies outlined in the Practice Aid.

Common Stock Valuation Methodologies

The valuations discussed below were prepared in accordance with the guidelines in the Practice Aid, which prescribes several valuation approaches for setting the value of an enterprise, such as the cost, market and income approaches, and various methodologies for allocating the value of an enterprise to its common stock. We generally used the market approach, in particular the guideline company and precedent transaction methodologies, based on inputs from comparable public companies’ equity valuations and comparable acquisition transactions, to estimate the enterprise value of our company.

Methods Used to Allocate Our Enterprise Value to Classes of Securities

In accordance with the Practice Aid, we considered the various methods for allocating the enterprise value across our classes and series of capital stock to determine the fair value of our common stock at each valuation date. The methods we considered consisted of the following:

 

   

Current Value Method. Under the current value method, once the fair value of the enterprise is established, the value is allocated to the various series of preferred and common stock based on their respective seniority, liquidation preferences or conversion values, whichever is greatest.

 

   

Option Pricing Method. Under the option pricing method, shares are valued by creating a series of call options with exercise prices based on the liquidation preferences and conversion terms of each equity class. The values of the preferred and common stock are inferred by analyzing these options. The total equity value allocated to the common stock is then divided by the number of shares outstanding at each valuation date to determine the fair value per share. In addition, since our stock is not publicly traded, a discount for lack of marketability is then applied to determine the fair value of our common stock.

 

   

Probability-Weighted Expected Return Method, or PWERM. The PWERM is a scenario-based analysis that estimates the value per share based on the probability-weighted present value of expected future investment returns, considering each of the possible outcomes available to us, as well as the economic and control rights of each share class.

Contemporaneous Valuations

December 31, 2011 and January 31, 2013 Common Stock Valuation

We obtained contemporaneous valuations of our common stock on December 31, 2011, or December 2011 valuation, and January 31, 2013, or January 2013 valuation, to assist our board of directors in estimating the fair value of our common stock on subsequent grant dates. These contemporaneous valuations used the income approach, implementing a discounted cash flow, or DCF, analysis, to determine the enterprise value of the company and the option pricing method to allocate the enterprise value to the common stock. The DCF analysis involves applying appropriate discount rates to estimated cash flows that were based on forecasts of revenue, costs and capital requirements. Our assumptions underlying the estimates were consistent with the plans and estimates that we use to manage the business. The risks associated with achievement of our forecasts were assessed in selecting the appropriate discount rates and selecting probability weights for forecasted cash flows. To derive the value of the common stock under the DCF, the proceeds to the common stockholders were calculated based on the preferences and priorities of the preferred and common stock.

The enterprise value determined by the DCF method was allocated by utilizing the option pricing method. For purposes of the December 2011 and January 2013 valuations, we relied on the following key assumptions in applying the option pricing method:

 

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We estimated volatility based on guideline publicly-traded companies with an expected term consistent with the timeline to the liquidity event.

 

   

We estimated a weighted-average time to a sale event of 1.50 years based on the projected time to significant clinical development events for our drug candidates, which remained unchanged between the December 2011 and January 2013 valuations as the clinical development of our drug candidates had not proceeded during that period as we had anticipated at the time of the December 2011 valuation.

 

   

We determined the risk-free interest rate based on the yield of a U.S. Treasury bill with a maturity date closest to the estimated time to a sale event for our stockholders.

 

   

We applied a discount for lack of control and marketability of 30%, which reflected the highly illiquid nature of our common stock as well as the lack of control possessed by common stockholders in light of the rights and privileges of our preferred stock, including anti-dilution protection, redemption rights, protective provisions in our certificate of incorporation and rights to participate in future rounds of financing.

The resulting estimated fair value of our common stock as of December 31, 2011 was $2.52 per share and as of January 31, 2013 was $2.78 per share.

June 1, 2013 Common Stock Valuation

We obtained another contemporaneous valuation of our common stock on June 1, 2013, the June 2013 valuation. The June 2013 valuation utilized the PWERM valuation methodology to allocate the enterprise value to the common stock. Under this method, the value of the common stock is estimated based upon an analysis of future values for our company assuming various investment outcomes, the timing of which is based, in part, on the plans of our board of directors and management. Under this approach, share value is derived from the probability-weighted present value of expected future investment returns, considering each of the possible outcomes available to us, as well as the economic and control rights of each share class. The fair value of our common stock was estimated using a probability-weighted analysis of the present value of the returns afforded to common stockholders under several future stockholder exit or liquidity event scenarios, either through (1) an IPO; (2) a trade sale of our company at a premium to cumulative amounts invested by preferred stock investors; or (3) a trade sale of our company at a value below the cumulative liquidation preference of the preferred stockholders.

For the June 2013 valuation, significant assumptions for the PWERM included the probability of occurrence of each scenario, timing to the liquidity event, discount rate and discount for lack of marketability. The key valuation assumptions included those noted in the following table:

 

June 1, 2013

Major Assumptions

   IPO
Short-Term
     IPO
Long-Term
     Trade Sale
– High
     Trade Sale
– Low
     Sales below
Liquidation
Preference
 

Probability of Scenario

     50%         10%         15%         15%         10%   

Discount for Marketability

     0%         0%         20%         20%         20%   

Timeline to Liquidity

     0.42 yrs         0.92 yrs         2.5 yrs         2.5 yrs         2.5 yrs   

Discount Rate – Common Stock

     30%         30%         30%         30%         30%   

The selected enterprise value in the short-term scenario was based on the pre-money market data for initial public offerings between the third quartile and the maximum of the observed range. The selected aggregate enterprise value in the long-term scenario was based on consideration of the high-end of the observed range of transaction values. The selected enterprise value utilized in the base-case scenario considered the median of the observed range of comparable transaction values. The selected enterprise value for the high-case scenario was based on the comparable transaction values between the third quartile and the high-end of the observed range. In the sale at a price below liquidation preference scenario, the June 2013 valuation assumed a value that would not allow the preferred stockholders to realize their full liquidation preference resulting in no value to common stockholders.

 

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Under all the exit scenarios considered in the PWERM, the fair value of our common stock was calculated using the estimated future enterprise valuations and a risk-adjusted discount rate based on the inherent risk of a hypothetical investment in our common stock, and a discount for lack of marketability. The risk-adjusted discount rate was based on consideration of the weighted-average cost of capital, or WACC, for comparable biotechnology companies adjusted for company specific risk factors, the venture capital rates of return detailed in the Practice Aid, and an analysis of other quantitative and qualitative factors considered pertinent to estimating the discount rate. We determined the discount for marketability using legal guidelines from U.S. Tax Court cases regarding privately-held business valuations, fundamental business factors and empirical studies on the discount for lack of marketability. We corroborated the discount based on the value of a put option compared to the value of common stock using a Black-Scholes option-pricing model. We also considered the rights and privileges of our preferred stock as compared to our common stock, including anti-dilution protection, redemption rights, protective provisions in our certificate of incorporation and rights to participate in future rounds of financing.

The resulting estimated fair value of our common stock as of June 1, 2013 was $9.36 per share.

Retrospective Valuations

September 1, 2012 and April 1, 2013 Retrospective Valuations

In preparing for our proposed initial public offering, we determined that retrospective valuations of the fair value of our common stock as of September 1, 2012 and April 1, 2013 were appropriate due to the acceleration of the timeframe to a potential liquidity event. In connection with that reexamination, we obtained retrospective valuations of the fair value of our common stock for financial reporting purposes to assist our board of directors in re-evaluating the fair value of our common stock as of these dates. We did not retrospectively value options granted prior to September 1, 2012 because the impact of any re-assessment would be immaterial.

Similar to the June 2013 valuation, the retrospective valuations at September 1, 2012 and April 1, 2013, used the PWERM to allocate the enterprise values to the common stock at that date.

For purposes of these retrospective valuations, the selected enterprise value in the short-term scenarios was based on the pre-money IPO market data for transactions between the third quartile and the maximum of the observed range. The selected aggregate enterprise value in the long-term scenarios was based on consideration of the high-end of the observed range of transaction values. The selected enterprise value utilized in the base-case scenarios considered the median of the observed range of comparable transaction values. The selected enterprise value for the high-case scenarios was based on the comparable transaction values between the third quartile and the high-end of the observed range. In the sale at a price below liquidation preference scenarios, we assumed a value that would not allow the preferred stockholders to realize their full liquidation preference resulting in no value to common stockholders.

Under all the exit scenarios considered in the PWERM for these retrospective valuations, the fair value of our common stock was calculated using the estimated future enterprise valuations and a risk-adjusted discount rate based on the inherent risk of a hypothetical investment in our common stock, and a discount for lack of marketability. The risk-adjusted discount rate was based on consideration of the WACC for comparable biotechnology companies adjusted for company specific risk factors, the venture capital rates of return detailed in the Practice Aid, and an analysis of other quantitative and qualitative factors considered pertinent to estimating the discount rate. We determined the discount for marketability using legal guidelines from U.S. Tax Court cases regarding privately-held business valuations, fundamental business factors and empirical studies on the discount for lack of marketability. We corroborated the discount based on the value of a put option compared to the value of common stock using a Black-Scholes option-pricing model. We also considered the rights and privileges of our preferred stock as compared to our common stock, including anti-dilution protection, redemption rights, protective provisions in our certificate of incorporation and rights to participate in future rounds of financing.

 

 

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The specific facts and circumstances considered by our board of directors in assessing these key valuation assumptions for each of these retrospective valuations included those noted in the following tables:

 

September 1, 2012

Major Assumptions

   IPO
Short Term
     IPO
Long Term
     Trade Sale
– High
     Trade Sale
– Low
     Sales below
Liquidation
Preference
 

Probability of Scenario

     15%         20%         15%         20%         30%   

Discount for Marketability

     0%         0%         20%         20%         20%   

Timeline to Liquidity

     2.0 yrs         3.0 yrs         2.75 yrs         2.5 yrs         3.0 yrs   

Discount Rate – Common Stock

     30%         30%         30%         30%         30%   

April 1, 2013

Major Assumptions

   IPO
Short Term
     IPO Long
Term
     Trade Sale
– High
     Trade Sale
– Low
     Sales below
Liquidation
Preference
 

Probability of Scenario

     35%         15%         15%         20%         15%   

Discount for Marketability

     0%         0%         20%         20%         20%   

Timeline to Liquidity

     0.67 yrs         1.17 yrs         2.5 yrs         2.5 yrs         3.0 yrs   

Discount Rate – Common Stock

     30%         30%         30%         30%         30%   

The assumptions used for the PWERM in the April 1, 2013 valuation reflect an increase in the probability of a short-term IPO and decrease in the time to liquidity in light of the retrospective consideration of our progress towards our IPO at the time.

The resulting estimated fair value reflected in the retrospective valuations as of September 1, 2012 was $5.14 per share and as of April 1, 2013 was $8.26 per share.

Stock Option Grants

The dates of our contemporaneous valuations have not always coincided with the dates of our stock-based compensation grants. In determining the exercise prices of the options set forth in the table below, our board of directors considered, among other things, the most recent contemporaneous valuations of our common stock and our assessment of additional objective and subjective factors it believed were relevant as of the grant date. The additional factors considered when determining any changes in fair value between the most recent contemporaneous valuation and the grant dates included, when available, the prices paid in recent transactions involving our equity securities, as well as our stage of development, our operating and financial performance and current business conditions.

The following table summarizes stock options granted from January 1, 2012 through June 30, 2013:

 

Grant date

   Number of
common shares
underlying
options
granted
    Exercise Price
Per Common
Share
     Reassessed
deemed fair
value per
common share (1)
     Intrinsic
value
per common
share at
grant date
 

14-Feb-12

     41,603      $ 2.52       $ 2.52         —     

24-Apr-12

     131,142      $ 2.52       $ 2.52         —     

12-Jun-12

     344,536 (2)    $ 2.52       $ 2.52         —     

11-Aug-12

     117,159      $ 2.52       $ 2.52         —     

7-Sep-12

     444,479      $ 2.52       $ 5.14       $ 2.62   

16-Oct-12

     80,303 (2)    $ 2.52       $ 5.14       $ 2.62   

23-Apr-13

     126,546      $ 2.78       $ 8.26       $ 5.48   

28-Jun-13

     167,836      $ 9.36       $ 9.36         —     

 

(1) The fair value of our common stock was reassessed for financial reporting purposes subsequent to the grant date.

 

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(2) The performance vesting terms for a total of 204,773 shares underlying the June and October 2012 options included above were modified in March 2013 and resulted in a reassessed deemed fair value of $8.26 per share and related intrinsic value of $5.74 per share.

February 2012 to October 2012. Our board of directors granted options to purchase common stock on February 14, 2012, April 24, 2012, June 12, 2012, August 11, 2012, September 7, 2012 and October 16, 2012, with each option having an exercise price of $2.52 per share. In establishing this exercise price, our board of directors considered input from management, including the most recent contemporaneous valuation of our common stock, which was as of December 31, 2011, as well as the objective and subjective factors discussed above, including:

 

   

the results of preclinical studies and initial results from a Phase 1 clinical trial of BIND-014;

 

   

the addition of a new Chief Financial Officer;

 

   

the continued lack of liquidity of our common stock as a private company;

 

   

the absence of any capital raising transactions during this period;

 

   

the rights, preferences and privileges of our preferred stock as compared to those of our common stock, including the liquidation preferences of our preferred stock;

 

   

the impact of significant ongoing expenses associated with research and development and ongoing clinical trials; and

 

   

the low likelihood of achieving a liquidity event for holders of our common stock, such as an IPO or sale of our company, given our early stage of development and prevailing market conditions.

Our board of directors determined that, at each of the grant dates, the collective effect of these events and circumstances did not indicate a significant change in the fair value of our common stock. Based on these factors, our board of directors determined that the fair value of our common stock at each of the grant dates listed above was $2.52 per share.

Subsequently, our board of directors undertook a retrospective valuation of the fair value of our common stock as of September 1, 2012 for financial reporting purposes. We obtained a third-party retrospective valuation to assist our board of directors in reassessing the fair value of our common stock as of this date. In performing the retrospective valuation, we used PWERM to allocate the estimated enterprise value to our common stock and relied on the assumptions described above, which included a 15% probability of a short-term IPO and a 2-year time to liquidity for a short-term IPO. Our board of directors considered this retrospective valuation, together with the other factors described in the preceding paragraph, in making its retrospective determination of the fair value, which it determined to be $5.14 per share as of September 1, 2012. Our board of directors also considered the fair value of our common stock retrospectively as of October 16, 2012 and determined that there were no other internal or external value-generating events and circumstances that occurred between September 1, 2012 and October 16, 2012 that were indicative of a significant change in the fair value of our common stock. As a result, our board of directors determined that the retrospective fair value of our common stock as of October 16, 2012 was $5.14 per share.

April 2013. Our board of directors granted options to purchase common stock on April 23, 2013, with an exercise price of $2.78 per share. In establishing this exercise price, our board of directors considered input from management, including the valuation of our common stock as of January 31, 2013, as well as the objective and subjective factors described above, including:

 

   

the collaboration agreements we entered into with Amgen, Pfizer and AstraZeneca;

 

   

the issuance of five U.S. patents covering elements of BIND-014 and our medicinal nanoengineering platform;

 

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the addition of a new Chief Medical Officer;

 

   

the continued lack of liquidity of our common stock as a private company;

 

   

the prices of our preferred stock sold in arm’s length transactions, and the rights, preferences and privileges of our preferred stock as compared to those of our common stock, including the liquidation preferences of our preferred stock;

 

   

the impact of significant ongoing expenses associated with research and development and ongoing and planned clinical trials; and

 

   

an increase in the likelihood of our board of directors pursuing an IPO.

 

Based on these factors, our board of directors determined that the fair value of our common stock at April 23, 2013 was $2.78 per share.

Subsequently, our board of directors undertook a retrospective valuation of the fair value of our common stock at the time of the April 2013 option grants for financial reporting purposes. We obtained a third-party valuation to assist our board of directors in reassessing the fair value of our common stock as of this date. In performing this retrospective valuation, we again used PWERM to allocate the estimated enterprise value to our common stock and relied on the assumptions described above, which included, among others, a 35% probability of a short-term IPO and a 0.67-year time to liquidity for a short-term IPO. The changes in the assumptions used for the April 1, 2013 retrospective valuation as compared to the September 1, 2012 retrospective valuation reflect the continued acceleration of our progress towards an initial public offering. Our board considered that valuation together with the other factors identified in the preceding paragraph in determining the fair value. As a result, our board of directors determined that the retrospective fair value of our common stock as of April 1, 2013 was $8.26 per share.

June 2013. Our board of directors granted options to purchase common stock on June 28, 2013, with an exercise price of $9.36 per share. In establishing this exercise price, our board of directors considered input from management, including the valuation of our common stock as of June 1, 2013, as well as the objective and subjective factors outlined above. We used PWERM to allocate the estimated enterprise value to our common stock and relied on the assumptions described above, which included, among others, a 50% probability of a short-term IPO and a 0.42-year time to liquidity for a short-term IPO. The changes in the assumptions used for the June 1, 2013 valuation as compared to the April 1, 2013 retrospective valuation reflect the continued acceleration of our progress towards an initial public offering. Our board of directors determined that no events occurred between June 1, 2013 and the grant date that had not already been contemplated in the valuation as of June 1, 2013. The resulting value, which represented the estimated fair value of our common stock as of June 1, 2013, was $9.36 per share. This increase from our April 1, 2013 valuation of $8.26 per share was primarily due to the following factors:

 

   

we scheduled an organizational meeting for purposes of planning our IPO;

 

   

capital market conditions for biotechnology companies continued to improve as evidenced by a recent increase in the number of IPOs and their valuations, including increased valuations;

 

   

the NASDAQ Biotechnology (^NBI) index increased 12% from April 1, 2013 to June 1, 2013;

 

   

an increase in the likelihood of our board of directors pursuing an IPO; and

 

   

a decrease in the time to a prospective liquidity event.

Initial Public Offering

In consultation with the underwriters for this offering, we determined the estimated price range for this offering, as set forth on the cover page of this prospectus. The midpoint of the price range is $15.00 per share. In comparison, our estimate of the fair value of our common stock was $9.36 per share as of the June 1, 2013

 

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valuation. We note that, as is typical in IPOs, the estimated price range for this offering was not derived using a formal determination of fair value, but was determined by negotiation between us and the underwriters. Among the factors that were considered in setting this range were the following:

 

   

an analysis of the typical valuation ranges seen in recent IPOs for companies in our industry;

 

   

the general condition of the securities markets and the recent market prices of, and the demand for, publicly traded common stock of generally comparable companies;

 

   

an assumption that there would be a receptive public trading market for pre-commercial biotechnology companies such as us; and

 

   

an assumption that there would be sufficient demand for our common stock to support an offering of the size contemplated by this prospectus.

We believe that the difference between the fair value of our common stock as of June 1, 2013 and the midpoint of the price range for this offering is the result of these factors and the following factors and positive developments with respect to our business that occurred subsequent to June 1, 2013:

 

   

the PWERM method uses a probability weighted approach as described above, and the resulting estimate of the fair value of our common stock as of June 1, 2013 reflected the potential for alternative liquidity events, which decreases the estimated fair value due to the combination of (i) the mix of other expected business equity values that were lower in the alternative liquidity events scenario than in the IPO scenario and (ii) the application of a discount for lack of marketability; conversely, the midpoint of the estimated price range for this offering necessarily assumes only a single potential liquidity event, the IPO, and does not include a discount for lack of marketability, as an active trading market for the common stock will exist following the IPO. As a result, the midpoint of the estimated price range for this offering was neither reduced by other expected business equity values from other potential future liquidity events nor discounted for lack of marketability;

 

   

we activated the first investigative site for our Phase 2 clinical trial of BIND-014 in mCRPC in July 2013 and dosed the first patient in this trial in August 2013;

 

   

we dosed the first patient for our Phase 2 clinical trial of BIND-014 in NSCLC in July 2013;

 

   

we made progress in our ongoing Phase 1 dose escalation clinical trial of BIND-014, which trial is currently evaluating the Q1W dosing schedule; and

 

   

the NASDAQ Biotechnology (^NBI) index increased 9.2% from June 1, 2013 to August 29, 2013 and the market for initial public offerings of common stock of similarly situated biotechnology companies has been very favorable.

Based on the assumed initial public offering price of $15.00 per share, which is the midpoint of the price range set forth on the cover page of this prospectus, the intrinsic value of stock options outstanding as of June 30, 2013 would be $29.5 million, of which $12.7 million and $16.8 million would have been related to stock options that were vested and unvested, respectively, at that date.

Off-Balance Sheet Arrangements

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

Net Operating Loss and Research and Development Tax Credit Carryforwards

At December 31, 2012, we had federal, foreign and state tax net operating loss carryforwards of $26.1 million, $1.6 million and $31.9 million, respectively. The federal net operating loss carryforwards expire beginning in 2026 and ending in 2032. The state net operating loss carryforwards began expiring in 2012 and

 

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may continue to expire through 2032. At December 31, 2012, the Company had available income tax credits of approximately $2.4 million, which are available to reduce future income taxes, if any, through 2025 (state) and 2032 (federal).

Utilization of the net operating losses and credits may be subject to a substantial annual limitation due to ownership change limitations provided by the Internal Revenue Code of 1986, as amended. The annual limitation may result in the expiration of our net operating losses and credits before we can use them. We have recorded a valuation allowance on all of our deferred tax assets, including our deferred tax assets related to our net operating loss and research and development tax credit carryforwards.

JOBS Act

In April 2012, the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, was enacted. Section 107 of the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. Thus, an emerging growth company can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this extended transition period, and, as a result, we will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other public companies.

Quantitative and Qualitative Disclosures about Market Risk

The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates. As of June 30, 2013, we had cash equivalents of $21.3 million, consisting of interest-bearing money market accounts and prime money market funds. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. Due to the short-term maturities of our cash equivalents and the low risk profile of our investments, an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our cash equivalents. We are also subject to interest rate risk from the loans under the credit facility that bear interest at an annual rate equal to (a) 10.25% plus (b) the prime rate (as reported in the Wall Street Journal) minus (c) 3.25% subject to a floor of 10.25%.

In addition, we are subject to currency risk for balances held in rubles in our foreign subsidiary. We work to maintain all balances in U.S. dollars until payment in rubles is required to minimize this currency risk. Fluctuations in the exchange rate over the past 18 months has been about 30%. As of June 30, 2013, we held $4.2 million in Russian banks to support our Russian subsidiary, a portion of which is denominated in U.S. dollars. We contract with CROs internationally, primarily for the execution of clinical trials in Russia. Transactions with these providers are predominantly settled in rubles and, therefore, we believe that we have only minimal exposure to foreign currency exchange risks. We do not hedge against foreign currency risks.

We do not believe that inflation and changing prices had a significant impact on our results of operations for any periods presented herein.

 

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BUSINESS

Overview

We are a clinical-stage nanomedicine platform company developing Accurins, our novel targeted and programmable therapeutics. Accurins are designed with specified physical and chemical characteristics to target specific cells or tissues and concentrate a therapeutic payload at the site of disease to enhance efficacy while minimizing adverse effects on healthy tissues. Our strategy is to leverage our medicinal nanoengineering platform to develop our own pipeline of Accurins, initially in oncology, as well as Accurins in collaboration with biopharmaceutical companies. Our lead drug candidate, BIND-014, is in Phase 2 clinical trials for non-small cell lung cancer, or NSCLC, and metastatic castrate-resistant prostate cancer, or mCRPC. To date in 2013, we have announced collaborations with Amgen, Pfizer and AstraZeneca to develop Accurins based on therapeutic payloads from their product pipelines, with the potential to achieve a total of over $1 billion in upfront and future milestone payments, including over $450 million in pre-commercial milestones.

Our management team has extensive experience in the development, regulatory approval and commercialization of nanotechnology drugs. Currently, the two leading nanotechnology cancer drugs are Doxil, a liposomal doxorubicin, and Abraxane, an albumin nanoparticle paclitaxel. Our chief executive officer was the president and chief operating officer of SEQUUS Pharmaceuticals, Inc., the company that developed and commercialized Doxil. Both our chief medical officer and our head of regulatory affairs served in those roles at Abraxis Bioscience, Inc., the company that developed Abraxane. Our platform originated from the pioneering nanotechnology research at the Massachusetts Institute of Technology and Brigham and Women’s Hospital/Harvard Medical School of our scientific founders and directors Dr. Robert Langer and Dr. Omid Farokhzad. Our scientists and engineers continue to advance this technology to produce the next generation of targeted nanomedicines.

The challenge for all drugs is to maximize the net clinical benefit by increasing the desired therapeutic effect and reducing adverse effects. This is especially difficult in cancer, where the goal is to destroy or inhibit growth of cancer cells without damaging similar healthy cells. The first generation of cancer drugs were cytotoxic chemotherapies, such as Taxotere, which achieved limited selectivity by targeting mechanisms responsible for cell proliferation, a key characteristic of cancer cells. The mechanisms responsible for cell proliferation are also a property of healthy cells, which can lead to significant adverse effects when healthy cells are destroyed. Biopharmaceutical companies have developed more selective drugs, which we refer to as targeted therapies, such as Herceptin and Gleevec by targeting proteins found at higher levels on the surface of cancer cells or by inhibiting dysregulated biochemical pathways inside cancer cells. More recently, drugs such as Kadcyla have increased efficacy by linking toxins and antibodies to deliver targeted cytotoxicity. While these newer drugs were an improvement in targeting cancer cells relative to normal tissue, there continues to be a need to develop drugs with increased net clinical benefit.

We believe Accurins represent the next stage in the evolution of cancer therapy. Accurins are nanoparticles containing a therapeutic payload and are designed to target tumors at three levels: tissue, cellular and molecular. They combine this triple targeting with a prolonged circulation time to concentrate the therapeutic payload at the targeted disease site, where it is then released in a controlled and timely manner. Accurins have the potential to significantly increase the net clinical benefit of the therapeutic payload and result in efficacy and safety not currently achievable through other therapeutic approaches.

Our lead Accurin drug candidate, BIND-014, is a prostate-specific membrane antigen, or PSMA, targeted Accurin that contains docetaxel. PSMA is a clinically-validated tumor marker expressed on prostate cancer cells and the blood vessels of many types of non-prostate solid tumors, including NSCLC. Docetaxel, marketed as Taxotere, is one of the most commonly used cancer chemotherapy drugs. It is approved by the U.S. Food and Drug Administration, or FDA, for the treatment of breast cancer, NSCLC, mCRPC, head and neck cancer, and gastric cancer. Taxotere achieved global sales of approximately $3 billion in 2009, the year prior to its loss of marketing exclusivity in the United States, and generic docetaxel continues to be a mainstay in cancer treatment despite its

 

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significant side effects. These side effects include neutropenia, anemia, infection, fluid retention and edema, neuropathy, rash, mucositis, fatigue, muscle weakness, nail loss, hair loss and even death.

We are in Phase 2 clinical trials to evaluate the level of clinical activity of BIND-014 in NSCLC and mCRPC and expect to report data from these studies in the second half of 2014. To date, we have clinically tested BIND-014 in over 45 patients with advanced or metastatic cancer who failed prior therapies. In our Phase 1 clinical trial, of the 28 patients who received BIND-014 once every three weeks, to date there have been one complete response in a patient with cervical cancer and three partial responses in patients with NSCLC, mCRPC and ampullary cancer. A complete response generally refers to the disappearance of all signs of cancer in response to treatment, while a partial response generally refers to a decrease in the size of the tumor or in the extent of cancer in the body. Five additional patients had stable disease lasting longer than 12 weeks. In our preclinical studies, BIND-014 has demonstrated that its ability to destroy tumor cells is differentiated from, and superior to, Taxotere.

In addition to our internal development programs, we also consider opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. Our collaborations with industry leaders, including announced agreements with Amgen, Pfizer and AstraZeneca, provide us with the opportunity to develop Accurins with a broader range of therapeutic payloads than we could on our own. Our collaboration agreements generally require the collaborator to pay all the development costs associated with the Accurin, including those incurred by us. In addition, the upfront and potential milestone payments received under these agreements provide us with additional capital resources to develop our own proprietary pipeline of Accurins. We expect that at least one of our collaborations will advance an Accurin into the clinic by the end of 2014.

Our Strategy

Our goal is to become a leading biopharmaceutical company developing and commercializing targeted nanomedicines to address significant unmet medical needs, with an initial focus on treatments for cancer. The critical components of our business strategy include:

 

   

Develop our lead drug candidate, BIND-014, initially in NSCLC and mCRPC. BIND-014 is in two Phase 2 trials for the treatment of second-line docetaxel-naïve NSCLC and first-line chemotherapy-naïve mCRPC. These trials are single-arm, open label studies designed to evaluate efficacy and safety in these specific tumor types so that we can move into pivotal Phase 3 trials where we will seek to establish the superiority of BIND-014 versus docetaxel. Based on initial discussions with the FDA, we expect to use the 505(b)(2) FDA approval pathway and conduct a single Phase 3 trial for each indication using similar criteria for approval as docetaxel. The 505(b)(2) approval pathway would enable us to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of docetaxel when we submit our new drug application, or NDA, to the FDA. We will also evaluate the development of BIND-014 in other oncology indications, including breast cancer, and in combination with other cancer therapies.

 

   

Develop and commercialize Accurins in collaboration with leading biopharmaceutical companies. In addition to our internal development programs, we actively seek opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. We have established a number of collaborations with industry leaders, including announced agreements with Amgen, Pfizer and AstraZeneca.

 

   

Leverage our medicinal nanoengineering platform to develop a pipeline of high value Accurins. The modularity of our technology allows us to efficiently expand our pipeline of Accurins, both on our own and in collaboration with others, through various combinations of targeting ligands and therapeutic payloads, and also enables us to move into therapeutic areas beyond oncology, such as inflammatory and cardiovascular diseases.

 

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Capitalize on drug candidates with established drug development history to accelerate development and regulatory pathway. Where possible we seek to reduce the risk, cost and time associated with drug development by capitalizing on the known efficacy, safety and established drug development history of therapeutic payloads that have already been approved and others with promising attributes that have been deemed unsuitable for further development in their untargeted form. We seek to develop Accurins that could be eligible for accelerated regulatory pathways, such as 505(b)(2), fast track designation, accelerated approval, priority review and breakthrough product designation.

 

   

Commercialize proprietary Accurins, including BIND-014, directly in the United States and with collaborators outside the United States. We have retained the worldwide rights to BIND-014 and expect to initially maintain similar rights with respect to other proprietary Accurins we develop. We intend to build a focused oncology sales organization to market FDA-approved Accurins in the United States. Outside the United States, we expect to rely on collaborators to commercialize proprietary approved Accurins.

 

   

Continue to extend and protect our product technology and Accurins through our intellectual property portfolio. We seek to protect our medicinal engineering platform through 15 issued U.S. patents and 50 U.S. patent applications that we own or license, in some cases with foreign counterparts relating to elements of our Accurin candidates, as well as know-how and trade secrets relating to the design and manufacturing of our Accurins. We expect to file additional patent applications as we apply our technology to new targets and therapeutic payloads. In addition, we believe the heightened regulatory requirements for generic nanomedicines strengthen the protection afforded by our intellectual property portfolio.

Product Pipeline and Platform

We intend to use our medicinal nanoengineering platform to develop Accurins in several therapeutic areas, with an initial focus on the treatment of various types of cancer. In addition, we have entered into collaboration agreements with several major biopharmaceutical companies to develop and commercialize Accurins that are based on our collaborators’ proprietary therapeutic payloads. The following table depicts our proprietary and collaboration products in development:

 

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Evolution of Targeted Therapies

The challenge for all drugs is to maximize the net clinical benefit by increasing the desired therapeutic effect and reducing adverse effects. This is especially difficult in cancer, where the goal is to destroy or inhibit growth of cancer cells without damaging similar healthy cells. The first generation of cancer drugs were cytotoxic chemotherapies, such as Taxotere, which achieved selectivity by targeting mechanisms responsible for cell proliferation, a key characteristic of cancer cells. The mechanisms responsible for cell proliferation are also a property of healthy cells, which can lead to significant adverse events when healthy cells are destroyed. Biopharmaceutical companies developed more selective drugs such as Herceptin and Gleevec by targeting proteins found at higher levels on the surface of cancer cells or by inhibiting dysregulated biochemical pathways inside cancer cells.

A further step in the evolution of targeted therapies is antibody drug conjugates, or ADCs. ADCs consist of an antibody or antibody fragment and a chemically linked toxin. ADCs are designed to target antigens that are exclusively or preferentially expressed on the surface of cancer cells. The antibody causes the ADC to bind to the target cancer cells, where the ADC is required to be internalized by the cell in order to break the chemical link and release the toxin to kill the target cell. Because of the targeting, ADCs are expected to produce lower side effects and a greater net clinical benefit as compared to the toxin alone. Examples of ADCs include Adcetris, which is approved to treat relapsed and refractory Hodgkins lymphoma, and Kadcyla, which is approved to treat metastatic breast cancer.

The advent of targeted therapies has represented a major advance in the fight against important diseases including cancer. In some instances targeted therapies have displaced cytotoxic agents in standard cancer regimens and in others targeted therapies are now used in combination with cytotoxics. However, many targeted therapies are subject to the same limitations as cytotoxic agents, and despite the commercial and clinical success of targeted therapies, we believe the industry is increasingly recognizing potential limitations associated with these therapies, including:

 

   

Many molecularly-targeted therapies are directed toward cellular processes that are essential for cancer cell survival and proliferation, but also play important roles in normal cells. Because targeted drugs distribute throughout the body in much the same way as cytotoxic drugs, their clinical utility is often limited by toxicity.

 

   

The limited payload capacity of a monoclonal antibody requires that ADCs carry highly toxic payloads, restricting the universe of payloads that can be delivered. Most current ADCs in clinical development or on the market use one of a few highly toxic molecules such as maytansine, calicheamicin or aurastatin.

 

   

Since ADCs require the internalization of the antibody and the cleavage of the link between the antibody scaffold and the payload, ADCs must be targeted to antigens that are internalized by cancer cells at a rate sufficient to result in an effective intracellular concentration of the toxin.

As a result of these limitations, there continues to be a need to develop targeted therapies with increased net clinical benefit.

The Emergence of Nanomedicine

Recently, there has been a growing interest in the development of therapeutics using nanotechnology. Nanotechnology is the science and engineering of manipulating matter at the nanometer scale—one nanometer is one billionth of a meter. Nanomedicine is the medical application of nanotechnology to develop therapeutics with clinically useful chemical, physical and biological properties. There are several nanomedicine platforms at various stages of development or commercialization, many of which have limitations. Notable platforms include albumin nanoparticles, liposomes and polymeric nanoparticles.

 

   

Albumin nanoparticles utilize the plasma protein albumin to formulate therapeutic agents. Abraxane is an albumin nanoparticle paclitaxel that does not contain Cremophor, an excipient used in conventional solvent-based formulations of paclitaxel, such as Taxol. Abraxane has been effective at improving the net

 

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clinical benefit compared to conventional paclitaxel formulations by eliminating the side effects associated with the Cremophor and enabling higher dosing of paclitaxel. However, Abraxane has not been clinically shown to target any specific cellular target. The albumin nanoparticles separate from the paclitaxel upon administration, which then distributes widely throughout all tissues.

 

   

Liposomes encapsulate a therapeutic payload within a lipid shell. Liposomes can cross the walls of new or defective blood vessels and accumulate at the site of the disease. For example, Doxil, liposomal doxorubicin, has been approved for the treatment of multiple types of cancer and has been effective at improving the net clinical benefit by reducing cumulative cardiotoxicity and enabling a longer treatment period. Despite the success of Doxil, the widespread adoption of liposomal technologies has been limited by the difficulty in encapsulating different therapeutic payloads within the lipid shell and controlling their release. Liposomes have also proven difficult to manufacture at commercial scale.

 

   

Polymeric nanoparticles utilize synthetic polymers to attempt to create therapeutics that concentrate at the site of disease while minimizing exposure to healthy tissue, thereby increasing net clinical benefit. Polymeric nanoparticles vary with respect to whether they physically entrap or chemically attach the therapeutic payload to the polymer, the presence or absence of targeting ligands and the type of synthetic polymer used. Accurins are a member of this class of targeted therapies.

We believe nanomedicine holds the promise of combining the targeting specificity of monoclonal antibodies and ADCs with the breadth of applicability of traditional small molecule drugs and other therapeutics, thereby increasing the net clinical benefit for the treatment of cancer and other diseases.

Accurins

We believe Accurins represent the next stage in the evolution of targeted therapies and nanomedicine.

 

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Accurins are polymeric nanoparticles that incorporate a therapeutic payload and are designed to have prolonged circulation within the bloodstream, enable targeting of the diseased tissue or cells, and provide for the controlled and timely release of the therapeutic payload.

 

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Prolonged circulation. We design Accurins with a stealth and protective layer that enables them to circulate within the bloodstream for a prolonged period of time, and accumulate at the diseased site before being cleared from the circulatory system.

Targeting. We design Accurins with specific pharmaceutical properties intended to target tumors at three levels: tissue, cellular and molecular. Tissue targeting is achieved by engineering the physical and chemical properties—size, shape and surface properties—of the Accurin to allow it to escape through gaps in the blood vessels surrounding tumors and other disease sites. Cellular targeting is achieved using proprietary targeting ligands on the surface of the Accurin that binds to specific cell surfaces or tissue markers. The specific characteristics of the therapeutic payload may enable molecular targeting within the diseased cells. The following diagram depicts the mechanisms of tissue targeting and cellular targeting.

 

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Controlled and timely release. We design Accurins with specific polymers that provide for the controlled and timely release of the therapeutic payload. Upon administration, the therapeutic payload begins to diffuse through the polymeric matrix. Subsequently, the polymer breaks down to lactic acid, a compound naturally found in the body. If the therapeutic payload releases before the Accurins accumulate at the disease site, the Accurins will be unable to effectively increase drug concentration in the diseased tissue and the anticipated therapeutic impact will be minimized or lost. Similarly, if the therapeutic payload is not released, or releases too slowly, the anticipated therapeutic impact will be lost or minimized and new toxicities may be created.

By combining prolonged circulation, triple targeting and controlled and timely release of the therapeutic payload, Accurins have the potential to significantly increase the net clinical benefit associated with the therapeutic payload and result in efficacy and safety currently not achievable through other therapeutic modalities.

 

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These diagrams depict an Accurin and its key components:

 

LOGO   

 

•     Targeting ligands

 

•     Stealth and protective layer

 

•     Controlled-release polymer matrix

 

•     Therapeutic payload

LOGO   

•   Targeting ligands—To facilitate cellular targeting, we utilize a targeting ligand on the surface of the Accurin that binds to specific cell-surface or tissue markers, enabling the Accurins to preferentially accumulate at their intended site of action. Targeting ligands may include small molecules, peptides, antibodies and antibody fragments.

LOGO   

•   Stealth and protective layer—We have designed a stealth and protective layer for the Accurin using polyethylene glycol, or PEG, which is engineered to protect the Accurin from the body’s immune detection and clearance mechanisms by creating a hydration shell. PEG also provides attachment sites for the targeting ligand through linking chemistries.

 

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LOGO   

•   Controlled-release polymer matrix—We physically entrap the therapeutic payload in a matrix of clinically-validated, biodegradable and biocompatible polymers that mediate the release of the therapeutic payload at the disease site. The matrix is engineered, or programmed, to control the release of the therapeutic payload at a predetermined rate for the specific therapeutic payload and disease application.

LOGO   

•   Therapeutic payload—Our Accurins are designed to utilize a broad range of therapeutic payloads, including small molecules, peptides, proteins and nucleic acids, such as siRNA and mRNA.

In addition, the PEG and polymers used in our Accurins have been used in other medical products that have been approved by the FDA and other regulatory agencies.

Medicinal nanoengineering

We develop Accurins utilizing our medicinal nanoengineering platform. We engineer combinatorial libraries of targeted nanoparticles with systematically varied physical and chemical properties, such as particle size, surface properties, ligand density, therapeutic payload amount and release profile, using a self-assembly nanoparticle fabrication process. We design the Accurin to balance circulation time and payload release rate with effective targeting and binding for a particular cell or tissue target. We believe our platform allows us to advance an Accurin using an existing targeting ligand into preclinical testing in approximately four to six months after identifying a therapeutic payload.

Manufacturing of Accurins

Accurins are manufactured using a readily-scalable, self-assembly nanoemulsion process with well-defined, robust unit operations. This highly specialized and precisely controlled manufacturing process enables us to reproducibly manufacture Accurins across many scales, from gram-scale at the laboratory bench to hundreds of grams for investigational new drug application, or IND, enabling toxicology studies complying with the FDA’s good laboratory practice, or GLP, regulations to the multi-kilogram scale for clinical batches complying with FDA’s current good manufacturing practice, or cGMP, regulations. In addition, our well-controlled, self-assembly manufacturing process is the backbone of our medicinal nanoengineering platform, allowing us to take a combinatorial approach varying key nanoparticle parameters, such as drug load and release profiles, nanoparticle size/distribution and targeting ligand content, to identify Accurins for lead candidate selection. Our approach differs from common approaches to the preparation of nanoparticles that often employ multiple steps

 

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for drug incorporation and, separately, for the attachment of ligands to preformed nanoparticles, which create several challenges for reproducibility, yield and scalability. We have two U.S. issued patents and four U.S. patent applications relating to Accurin manufacturing processes.

We believe the design and manufacture of our Accurins allows us to create a targeted nanomedicine that achieves concentrations of therapeutic payload at disease sites unachievable through alternative therapeutic modalities to maximize therapeutic benefits.

Therapeutic Payloads

We have engineered Accurins that incorporate therapeutic payloads with a range of physicochemical properties. We have demonstrated in preclinical studies that these Accurins can improve tumor growth suppression, achieve higher concentrations of the payload in tumors compared to the payload administered in conventional form, and have pharmacokinetics and tolerability differentiated from their therapeutic payloads.

For example, we have incorporated the microtubule inhibitor vincristine into Accurins and observed differentiated pharmacokinetics and improved net clinical benefit compared to a conventional vincristine solution. In normal rats, the plasma concentration was more than 100 times higher in animals receiving vincristine Accurins compared to conventional vincristine. In cynomolgus monkeys, vincristine Accurins were well tolerated with minimal side effects at a vincristine dose that caused moribundity when administered in conventional form. In a mouse tumor model of human breast cancer, we observed an approximately 10-fold increase in tumor vincristine concentration and an approximately 2-fold increase in the maximum tolerated dose compared to conventional vincristine. At its maximum tolerated dose, a single dose of vincristine Accurins resulted in complete inhibition of tumor growth for the duration of the experiment, approximately 50 days after treatment, while conventional vincristine administered at its maximum tolerated dose inhibited tumor growth for approximately two weeks.

Similarly, we have incorporated the proteasome inhibitor bortezomib into Accurins and observed differentiated pharmacokinetics and improved net clinical benefit compared to a conventional bortezomib solution. In normal rats, the plasma concentrations were generally more than 100 times higher in animals receiving bortezomib Accurins compared to conventional bortezomib. In a mouse tumor model of human lung cancer, we observed up to an approximately 10-fold increase in tumor bortezomib concentration compared to conventional bortezomib. At equal doses in this model, bortezomib Accurins suppressed the tumor growth rate, while conventional bortezomib had no effect on tumor growth rate.

In addition, as part of our research and development work with collaborators, we have incorporated multiple kinase inhibitors into Accurins and observed differentiated pharmacokinetics and improved net clinical benefit in preclinical models compared to the parent forms of the therapeutic payloads. In normal rats, the plasma concentrations were more than 100 times higher in animals receiving Accurins compared to the payloads. In rodent models, these Accurins were well tolerated with reduced side effects. In rodent tumor models of human cancers, we observed up to 10-fold increases in tumor concentrations for the Accurin over the parent payloads and significantly prolonged activity. The Accurins resulted in complete inhibition of tumor growth at the termination point of the studies through the preferential targeting of payload to tumors and avoidance/reduction of toxicity in off-target healthy cells.

BIND-014

Our lead drug candidate, BIND-014, is an Accurin that targets PSMA and contains docetaxel. PSMA is a clinically-validated tumor antigen expressed on prostate cancer cells and the vasculature of most non-prostate solid tumors. Docetaxel is a clinically-validated and widely used cytotoxic agent that is FDA-approved for the treatment of breast cancer, NSCLC, mCRPC, head and neck cancer, and gastric cancer. We are in two Phase 2 clinical trials to evaluate the level of clinical activity of BIND-014, one in NSCLC and one in mCRPC.

 

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PSMA Targeting

PSMA is a transmembrane glycoprotein also known as glutamate carboxypeptidase II (GCPII) and N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I). Published preclinical and clinical data have shown PSMA to be preferentially expressed on prostate cancer cells and vasculature of non-prostate solid tumors as demonstrated in the table below. PSMA has not been found in normal vasculature, which makes it an attractive target for the treatment of solid tumors.

 

     Patients expressing PSMA      Number of U.S. patients  

Tumor

           Tumor Cells                       Tumor Vasculature                       Incidence                      Mortality          
Prostate      184/184 (100%)         2/12   (17%)         238,590         29,720   
Breast      0/6     (0%)         5/6   (83%)         232,340         39,620   
Colorectal      0/130     (0%)         110/130   (85%)         142,820         50,830   
Renal cell      0/75     (0%)         67/75   (89%)         65,150         13,680   
Bladder      8/167     (5%)         166/167   (99%)         72,570         15,210   
Gastric      0/119     (0%)         79/119   (66%)         21,600         10,990   
Neuroendocrine      0/5     (0%)         5/5 (100%)         1,000         420   
Melanoma      0/5     (0%)         5/5 (100%)         76,690         9,480   
Pancreatic duct      0/4     (0%)         4/4 (100%)         45,220         38,460   
NSCLC      0/5     (0%)         5/5 (100%)         193,961         135,558   

Soft tissue sarcoma

     0/6     (0%)         5/6   (83%)         11,410         4,390   

PSMA is a clinically-validated target in prostate cancer and is the target of an FDA-approved imaging agent, ProstaScint, and ADCs currently in clinical development. We plan to characterize PSMA expression levels in the tumors of patients enrolled in our Phase 2 clinical trials to evaluate the correlation between expression and efficacy as a potential basis for patient selection or a companion diagnostic.

Docetaxel

Docetaxel, marketed as Taxotere, is one of the most commonly used cancer chemotherapy drugs and was first approved by the FDA in 1996. It is approved for the treatment of breast cancer, NSCLC, mCRPC, head and neck cancer, and gastric cancer. Taxotere achieved global sales of approximately $3 billion in 2009, the year prior to its loss of marketing exclusivity in the United States, and generic docetaxel continues to be a mainstay in the oncology practice.

Docetaxel, the therapeutic payload in BIND-014, is more effective in some cancers versus others. For example, in metastatic breast cancer, single-agent docetaxel has a 30-60% response rate and six month progression-free survival. On the other hand, in second-line NSCLC, where it is one of the most commonly used chemotherapy agents, the response rate is only 5-9% with a progression-free survival of three months. The following table indicates the single-agent efficacy of docetaxel in various solid tumors based on several published clinical studies.

 

Indication

   Response Rate (%)(1)     Progression-Free Survival
(Months)
NSCLC (2nd Line)      5-9%      3
mCRPC      45-65%      6-8
Breast (1st Line Metastatic)      30-60%      6
Bladder (2nd Line)      13%      5
Cervix (2nd Line)      0-21%      2-3
Ovary (2nd Line)      20-25%      5
Biliary (1st-2nd Line)      0-20%      4-6
Gastric (2nd Line)      14%      2.6
Head and Neck (2nd Line)      27-43%      5-6.5

 

(1) Response rate is a reduction in tumor volume or, with respect to mCRPC, prostate-specific antigen, or PSA, levels.

 

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Docetaxel is associated with significant toxicities and side effects. These include neutropenia, anemia, infection, fluid retention and edema, neuropathy, rash, mucositis, fatigue, muscle weakness, nail loss, and hair loss. Market research suggests that many cancer patients, especially lung and prostate, who are elderly or have poor performance that are potentially eligible for docetaxel do not receive it because of concerns related to its toxicity.

BIND-014 Market Opportunity

Our initial development plan seeks to advance BIND-014 in both NSCLC and mCRPC. Both indications offer the opportunity to develop an improved standard of care as well as a substantive commercial opportunity. We will also evaluate the development of BIND-014 in other oncology indications, including breast cancer, which we estimate accounted for approximately 30% of the approximately four million docetaxel cycles administered in the United States in 2012, as well as in combination with other cancer therapies.

NSCLC

NSCLC remains an area of high unmet medical need. According to the National Cancer Institute, NSCLC is the number one cause of cancer related death in the United States, with annual mortality estimated to be approximately 136,000. Despite the numerous available therapies, the prognosis remains poor, with overall five-year survival for all patients diagnosed with NSCLC as low as 17%.

Current pharmacotherapy focuses on patients with locally advanced or metastatic NSCLC. Of the approximately 160,000 patients diagnosed with NSCLC in the United States each year, according to the National Cancer Institute’s SEER Cancer Database approximately 130,000 patients fall within the locally advanced or metastatic group and are thus eligible for therapeutic treatment.

The treatment paradigm for NSCLC focuses on increasing overall survival and other therapeutic benefits, and includes various molecularly-targeted therapies as well as a foundation of chemotherapy. The most common mutation found in patients with NSCLC occurs in the KRAS gene, for which there are currently no approved targeted therapies. Another mutation in NSCLC patients occurs in epidermal growth factor receptor, or EGFR. Patients who are found to have EGFR mutations are also treated with molecularly-targeted therapies including erlotinib and gefitinib. In addition, a small subset of patients has a mutation in anaplastic lymphoma kinase gene, or ALK, and is similarly treated with molecularly-targeted therapies such as crizotinib as well as standard chemotherapy. While such treatments represent a significant medical advance, treatment commonly results in escape mutations, or the selecting out of cancer cells that are resistant to treatment, resulting in patients becoming refractory to therapy.

Despite the introduction of molecularly-targeted therapies, chemotherapy remains the mainstay of NSCLC therapy. Current first-line therapy for advanced and metastatic NSCLC consists of platinum-based chemotherapy such as cisplatin or carboplatin. Second-line chemotherapy for NSCLC has included docetaxel, as well as other chemotherapy agents such as gemcitabine and vinorelbine. We estimate, based on our market research, that approximately 85,000 patients with advanced NSCLC receive taxanes annually, with approximately 35% of these patients receiving docetaxel.

Even with widespread use in the second-line treatment for NSCLC, docetaxel suffers from very poor efficacy in this cohort of patients. Response rates range from 5-9%, with a median survival benefit of 2.9 months versus best supportive care. By concentrating docetaxel at the tumor site, we believe that BIND-014 will be able to achieve superior efficacy to docetaxel in this setting, without worsening the resultant side effect profile.

 

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mCRPC

Prostate cancer is one of the most prevalent male cancers in the United States, with more than 2.6 million men in 2010 having the disease. In contrast to NSCLC, patients with prostate cancer often have a good prognosis, with a five-year survival rate of approximately 100% for those that have local disease.

Pharmacotherapy is reserved for those patients that have a recurrence of their disease following initial radiation or surgery and the minority of patients that present with metastatic disease. The mainstay of current treatment for these patients is hormone therapy, with front-line treatment accounted for by gonadatropin releasing hormone, or GnRH, agonists such as goserilin. By starving the prostate of sex hormones, GnRH agonists achieve chemical castration, thus removing a vital stimulus for tumor growth. However, based on published data, we estimate that 30,000 patients per year become resistant to such treatment and are deemed to have CRPC. Most of these patients progress to mCRPC.

Prior to 2004, all treatments for mCRPC were considered palliative and not shown to prolong survival. However, a number of agents, including docetaxel, have now been shown to prolong survival. Docetaxel currently forms the foundation chemotherapeutic treatment for the approximately 20,000 mCRPC patients that receive chemotherapy. Docetaxel has a relatively high PSA response rate in mCRPC, of the order 45-48%, and leads to a median survival benefit of 2.4 months versus mitoxantrone, another chemotherapy agent. It is, however, limited by substantial side effects, and as a result of the significant co-morbidities associated with the elderly mCRPC population, is often not prescribed to or tolerated by these patients.

According to a Swedish population-based study published in the 2013, between May 2009 and December 2010 61% of men less than 70 years of age received chemotherapy while only 30% of men aged 70-79 and 5% of men over the age of 80 received chemotherapy despite being eligible for chemotherapy treatment. We estimate further, based on market research and payer utilization data, that approximately 20% of docetaxel cycles are administered for mCRPC. For patients that relapse following docetaxel, cabazitaxel is often used as the second-line chemotherapeutic agent. In 2012, in its third year of launch, worldwide cabazitaxel sales were €235 million.

More recently, the advent of newer drugs acting on the hormonal cascade has provided patients with an added treatment option. Second-line hormonal agents include abiraterone and enzelutamide. While the main use of such treatments remains in the post-chemotherapy setting, it is anticipated that they will find increased use earlier in the treatment paradigm in both the pre-chemotherapy mCRPC setting and potentially the non-metastatic CRPC setting. Given the sequential nature of prostate cancer treatment, we do not anticipate such advances to substantially impact the usage of chemotherapy.

In the context of mCRPC, we believe BIND-014’s potential to increase the net clinical benefit of docetaxel could result in an Accurin at least as potent as docetaxel but with a differentiated side effect profile. Given docetaxel’s propensity for severe adverse events, we believe a more tolerable alternative to docetaxel could not only win market share but also potentially expand this large market opportunity by addressing patients currently too sick to receive docetaxel.

BIND-014 Development

We have completed preclinical and initial clinical development of BIND-014. The performance of BIND-014 in preclinical studies suggests that BIND-014 is highly differentiated from, and superior to, Taxotere. We are conducting a Phase 1 clinical trial evaluating two dosing schedules: once every three weeks, or Q3W, and once weekly for three weeks followed by one week of no treatment over a four-week cycle, or Q1W. In the now complete Q3W dosing portion of the study in which 28 patients were treated, one patient had a complete response and three patients showed partial responses. Five additional patients had stable disease lasting longer than 12 weeks. We believe that these initial efficacy results reflect the differentiating pharmacology compared to docetaxel observed in preclinical and clinical studies. The Q1W portion of the study is ongoing. We have initiated Phase 2 development of BIND-014 in NSCLC and mCRPC on the Q3W dosing schedule. We are also considering additional clinical studies to evaluate BIND-014 in other tumor types.

 

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Phase 2 and Clinical Development Plan

Our overall objective for BIND-014 is to establish it as a safe and effective new cancer therapy with superior efficacy to docetaxel in tumor types where Taxotere is already approved. As a result, we initiated two Phase 2 trials of BIND-014 at the Q3W dosing schedule in the second quarter of 2013:

 

   

40 patient open label, single arm, multi-center trial designed to determine the efficacy of BIND-014 as measured by objective response rate in patients with late stage NSCLC who have failed one prior platinum-containing chemotherapy regimen for advanced or metastatic disease; and

 

   

40 patient open label, single arm, multi-center trial designed to determine the efficacy of BIND-014 as measured by progression-free survival in patients with mCRPC who are chemotherapy naïve.

These clinical trials are expected to take approximately 12 months to enroll, and will be conducted at multiple clinical sites in the United States and Russia. If we obtain favorable results in these Phase 2 studies, we plan to initiate pivotal trials of BIND-014 in early 2015 in both mCRPC and second-line NSCLC. We anticipate these will be head-to-head randomized Phase 3 trials of BIND-014 compared to docetaxel in these indications and will be designed to demonstrate the superiority of BIND-014.

Phase 1 Clinical Development

We are conducting a Phase 1 clinical trial evaluating BIND-014 in patients with advanced and metastatic solid tumors at Q3W and Q1W dosing schedules. We have completed the Q3W portion of the trial, and the Q1W dose escalation is ongoing.

The study is designed to enroll individual cohorts of one to three patients at a starting dose and, if no dose limiting toxicities, or DLTs, are observed, the dose is increased to the next pre-specified dose level for the next cohort of patients until a maximum tolerated dose is identified. As long as there is no disease progression, patients are allowed to stay on drug; however, since the starting dose is typically sub-therapeutic we expected patients’ tumors in the early cohorts to continue to grow. In the Q3W portion of the study, we evaluated dose levels ranging from 3.5 mg/m2 to 75 mg/m2. The Q3W portion of the study enrolled 30 patients with a variety of advanced malignancies. Of those 30, 28 patients were evaluable for toxicities at six different dose levels. The other two patients had disease progression before their first dose of BIND-014. All of the patients in the study previously failed standard therapies for their disease. The study included patients with NSCLC, head and neck cancer, mCRPC and a variety of gastrointestinal and other malignancies.

In the Q3W portion of the study, BIND-014 was well tolerated with predictable and manageable toxicities and we did not observe any new or unexpected toxicity with BIND-014. Twenty five patients experienced a treatment-related adverse event, with one such event resulting in death. Three patients discontinued treatment as a result of treatment-related adverse events. The most common adverse event was neutropenia, or a low number of white blood cells, which occurred in 10 patients. The one death in the trial was an elderly patient with advanced biliary cancer and a biliary stent who was treated with BIND-014 at 75 mg/m2 dosing and developed sepsis as a consequence of neutropenia, which has previously been observed in clinical studies of patients receiving docetaxel. Other treatment-related adverse events included fatigue, diarrhea, anemia, hair loss, infusion related reaction, dehydration, nausea and vomiting. These treatment-related adverse events and their frequency are generally consistent with the treatment-related adverse events associated with docetaxel as well as many other cancer drugs. In light of the similarity with other FDA-approved cancer therapeutics, we believe our Phase 1 results to date suggest an acceptable safety profile at this stage of development. We determined the maximum tolerated dose to be 60 mg/m2 given as a 60 minute infusion Q3W based on the observed toxicity profile.

Neutropenia is frequently associated with docetaxel therapy as well as many other chemotherapy drugs, and is an expected toxicity of BIND-014. Docetaxel is typically dosed clinically at 75 mg/m2 and often administered in conjunction with growth factor support to abrogate neutropenia. We believe the neutropenia we have observed with BIND-014 is a result of systemic exposure to released docetaxel.

 

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The pharmacokinetic profile of the Q3W dose group translated well from preclinical studies and showed a linear relationship of dose level to blood concentration. As expected from the preclinical data, the pharmacokinetic profile of BIND-014 observed in this study is differentiated from that of published pharmacokinetic data for conventional docetaxel. The plots below depict the docetaxel plasma concentrations of BIND-014 administration at various dose levels, and compare the BIND-014 plasma concentration profile at one dose to historical data for the same dose of conventional docetaxel.

 

LOGO

Baker, et al., Clin Cancer Res, vol. 10, p1976, 2004

The Phase 1 study is also evaluating preliminary anti-tumor activity. Anti-tumor activity was assessed every other dose cycle using the criteria established by Response Evaluation Criteria in Solid Tumors (RECIST) or, with respect to mCRPC, by evaluating PSA levels. RECIST is a set of published rules that define when cancer patients improve, stay the same or worsen during treatments. Of the 28 patients treated at Q3W dosing, to date there has been one complete response in a patient with cervical cancer and three partial responses in patients with NSCLC, mCRPC and ampullary cancer. These responders received either 60mg/m2 (NSCLC and prostate cancer) or 75 mg/m2 (ampullary and cervical cancer). The two responders at 75mg/m2 were subsequently dosed reduced to 60 mg/m2 and continued to experience benefit. In addition, five of the 28 evaluable patients had stable disease lasting at least 4 cycles, or 12 weeks or longer, with the following cancers: tonsillar, anal, mCRPC, pancreatic and gall bladder. None of the responders had prior taxane exposure. A complete response under RECIST means the disappearance of all tumor lesions. A partial response under RECIST means that there has been at least a 30% decrease in the sum of the diameters of measured tumor lesions, taking as reference the baseline sum diameters, and that there has been no growth of new or non-measurable tumor lesions. Stable disease under RECIST means that there has been less than a 30% decrease and no more than a 20% increase in the sum of the diameters of measured tumor lesions, taking as reference the smallest sum of measured tumor lesions since treatment started, and that there has been no growth of new target or non-measurable tumors. A partial response for mCRPC patients means a decrease in the extent of cancer in the body as measured by PSA levels.

The portion of the Phase 1 trial that is ongoing is evaluating BIND-014 on a Q1W doing schedule. We are evaluating administration with this cycle as: (1) conventional docetaxel has been evaluated extensively in both Q3W and Q1W schedules and Q1W schedules are associated with less neutropenia; (2) our pharmacokinetic profile suggests we can administer BIND-014 weekly; (3) preclinical studies of BIND-014 in animals suggest less neutropenia when administered weekly; and (4) weekly dosing may allow for greater drug exposure which potentially could have a positive effect on efficacy. This portion of the Phase 1 trial is still ongoing and actively recruiting patients. As of August 27, 2013, 26 patients with a variety of cancers have been dosed on the Q1W schedule, at dose ranges from 15-45 mg/m2. To date, the weekly schedule has been well tolerated. Dose limiting

 

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toxicity has been observed in two patients (neutropenic fever, mucositis) at the 45mg/m2 level. This trial will continue to accrue patients until the maximum tolerated dose is established. Once the Q1W maximum tolerated dose is established, and we evaluate the results, we may amend our Phase 2 trials to add a Q1W arm.

Preclinical Development

Prior to entering clinical development, we completed preclinical studies in mice, rats and nonhuman primates to evaluate the accumulation of BIND-014 at the targeted disease site, the effects of prolonged circulation of BIND-014 and the impact of BIND-014 on tumor size and growth. The performance of BIND-014 in these preclinical studies suggests that BIND-014 is highly differentiated from, and superior to, Taxotere.

We compared the pharmacokinetics of BIND-014 and Taxotere in cynomolgus monkeys. In the study, equal doses of BIND-014 or Taxotere were administered to animals and blood samples collected at various times over a 70-hour period were analyzed to measure the total docetaxel concentration. The docetaxel concentration was approximately 10 to 100 times higher with BIND-014 than Taxotere for the entire duration of the experiment. These data suggest that BIND-014 prolongs the retention of docetaxel in the circulation, making it available to disseminate into tumor sites. Similar findings have been obtained in other animal species, including mice and rats. The following graph depicts the levels of docetaxel concentration in studied cynomolgus monkeys over the 70-hour study period administered at the same dose. The first measurement of docetaxel shown below is lower due to the rapid diffusion upon administration.

 

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We also studied the levels of accumulation of docetaxel in a mouse model of human prostate cancer when treated with BIND-014 or Taxotere. Prostate tumor-derived cells were implanted in mice and allowed to form tumors. The mice were then treated with equal doses of either BIND-014 or Taxotere. Tumors were harvested at two and 12 hours after docetaxel administration and analyzed for total docetaxel concentration. After two hours, the docetaxel concentration in tumors was higher in animals that received BIND-014, but not statistically different from docetaxel. After 12 hours, the docetaxel concentration was more than seven times higher in the animals treated with BIND-014 (p<0.01). Between two and 12 hours, the concentration of docetaxel in tumors increased in animals treated with BIND-014, but decreased in the animals treated with Taxotere. The following graph depicts the results of this study.

 

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We believe that the increase in the concentration of docetaxel in tumors in mice treated with BIND-014 is due to the combined effects of prolonged circulation time of BIND-014, extravasation of BIND-014 into tumors through defects in the tumor blood vessels, binding of the particles to PSMA and controlled release of docetaxel.

 

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We also compared the efficacy of BIND-014, a version of BIND-014 without targeting ligand, which we refer to as PTNP, and docetaxel in mouse models using the LNCaP human prostate cancer cell line and the MX-1 human breast cancer cell line. Tumor cells were implanted in mice and allowed to form tumors. Different groups of mice were then treated every four days with equal doses of either BIND-014, PTNP, docetaxel, or a solution containing no docetaxel, which we refer to as vehicle. In the prostate cancer model, mice received four doses over 16 days. In the breast cancer model, three doses were administered over 12 days. The size of the tumors were periodically measured to determine the effect of treatment on the rate of tumor growth or shrinkage. In both tumor models, while Taxotere slowed down the rate of tumor growth compared to vehicle, the tumors still increased in size, particularly after treatment was discontinued. BIND-014 treatment resulted in significantly increased shrinkage of the tumors when compared to docetaxel, which persisted even after treatment was stopped (p<0.05 in prostate cancer model, p<0.01 in the breast cancer model). BIND-014 was also significantly more effective than PTNP in the prostate cancer model, which expresses PSMA (p<0.05). BIND-014 and PTNP docetaxel nanoparticles were equally effective in the breast tumor model, which does not express PSMA. We attribute the improved efficacy of BIND-014 to the increased docetaxel concentration in tumors resulting from accumulation of BIND-014 particles via tissue and cell targeting. The following graphs provide the results of the prostate and breast cancer tumor studies.

 

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BIND-014 Regulatory Pathway

We expect to use the FDA’s 505(b)(2) regulatory pathway as well as the European Medicines Agency’s, or EMA’s, hybrid application pathway, which would allow an abbreviated pathway to approval for BIND-014. Section 505(b)(2) of the Federal Food Drug & Cosmetic Act, or FDCA, enables an applicant to rely, in part, on the FDA’s findings of safety and efficacy for an existing product, or published literature, in support of its NDA. Section 505(b)(2) NDAs often provide an alternate regulatory pathway to FDA approval for new or improved formulations or new uses of previously approved products. Docetaxel is not chemically modified but physically encapsulated in our Accurin, and preliminary discussions with the FDA suggest that BIND-014 qualifies for the 505(b)(2) pathway. This pathway would allow us to reference both preclinical and clinical information that was part of the original registration filing on the active drug, Taxotere, and would allow for potential approval based on a single pivotal trial designed with the same endpoints as the reference compound. However, unlike most 505(b)(2) pathway approaches, we will be powering our pivotal trials with the goal of demonstrating superiority over docetaxel. In this way, the 505(b)(2) pathway offers us the opportunity to obtain FDA approval for BIND-014, and other Accurins based on already approved drugs, at a lower cost and in a shorter period of time than is typically possible for new chemical entities.

Collaborations

In addition to our internal development programs, we also consider opportunities to collaborate with recognized biopharmaceutical companies to develop Accurins incorporating therapeutic payloads from their proprietary product portfolios. We have established a number of collaborations with biopharmaceutical

 

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companies, including announced agreements with Amgen, Inc. Pfizer, Inc. and AstraZeneca AB to develop Accurins based on their therapeutic payloads. These collaborations include five of the top ten oncology targets as measured by the number of programs in the biopharmaceutical industry targeting these mechanisms. These collaborations provide us with the opportunity to expand our platform by developing Accurins with a broader range of therapeutic payloads than we could on our own. Our collaboration agreements generally require the collaborator to pay all the development costs associated with the Accurin, including those incurred by us. In addition, the upfront and potential milestone payments received under these agreements provide us with additional capital resources to develop our own proprietary pipeline of Accurins. Aggregate upfront and contingent clinical, regulatory and marketing milestone payments under these agreements are over $1 billion, exclusive of potential royalties. Over $450 million of these potential milestones are pre-commercial, of which approximately $11 million are pre-IND, approximately $190 million are clinical development and approximately $250 million are regulatory milestones. We expect that at least one of our collaborators will advance an Accurin into the clinic by the end of 2014.

We generally consider each of the following criteria when evaluating a potential collaborator and its proposed therapeutic payload:

 

   

The physical and chemical properties of the proposed therapeutic payload are well suited for encapsulation and release in an Accurin;

 

   

The therapeutic payload has high therapeutic potential for addressing an important unmet medical need;

 

   

The therapeutic payload is highly validated in its original, untargeted form;

 

   

The collaborator possesses substantial resources and capabilities for contributing to the development and commercialization of our collaboration product;

 

   

The collaborator places strategic importance on our collaboration product in their portfolio;

 

   

The collaborator is committed to our project as demonstrated by the sponsorship of their executive management; and

 

   

The collaborator values our relationship and ongoing input in the development of the collaboration product.

Amgen

In January 2013, we entered into a license agreement with Amgen, Inc., pursuant to which we granted to Amgen an option to obtain an exclusive worldwide license to develop, manufacture and commercialize an Accurin incorporating a specified Amgen kinase inhibitor for all uses except for some vaccine applications. Amgen may exercise its option during a period of approximately 12 months, beginning on the effective date of the agreement, by paying us a specified option exercise fee. If Amgen fails to exercise its option within such time period, then we have the right to exercise an exclusive option to obtain a license from Amgen to develop, manufacture and commercialize Accurins containing the Amgen kinase inhibitor on terms to be mutually agreed.

We and Amgen are each responsible for using commercially reasonable efforts to develop licensed products under a development plan. If Amgen exercises its option, it will be solely responsible for all further development and commercialization activities, and must use commercially reasonable efforts to develop, seek regulatory approval for, and commercialize at least one licensed product. We are responsible for manufacturing licensed compounds for use in preclinical studies, and we will collaborate with Amgen in developing and implementing a strategy for subsequent manufacturing. Until Amgen’s option expires, we may not develop any nanotherapeutic against the same target as Amgen’s drug candidate; however, if Amgen exercises its option, it must pay us an annual fee to maintain this target exclusivity. This annual fee will total $54.0 million over a ten-year period following exercise of the option by Amgen, if at all, subject to Amgen’s annual election to maintain exclusivity, and will continue to be payable so long as Amgen continues such election. If Amgen defers its initial election for extended exclusivity until after the expiration of the option period, Amgen will be obligated to pay 200% of each such annual amount.

Under our agreement with Amgen, we received an upfront payment of $5.0 million and have the potential to receive contingent payments for up to two indications totaling up to $111.5 million in the aggregate upon

 

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exercise of the option and achievement by Amgen of specified development and regulatory events with respect to such indications, plus additional contingent payments totaling up to $188 million in the aggregate upon the achievement by Amgen of specified commercial events with respect to such indications. If Amgen exercises its option, Amgen will reimburse us for all external expenses we incur relating to the agreement after such exercise. We will also receive tiered royalties in the mid-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed products. We will receive royalties on a country-by-country and licensed product-by-licensed product basis generally until the expiration of the Amgen patents covering such licensed product. Amgen is also obligated to pay certain development costs.

The agreement will remain in effect, on a country-by-country and licensed product-by-licensed product basis, until Amgen’s obligation to pay us royalties ends. If the agreement expires with respect to a licensed product in a country, any licenses granted by us to Amgen will become perpetual, irrevocable and fully paid up with respect to such licensed product in such country. Either Amgen or we may terminate the agreement for the other party’s uncured material breach or insolvency, Amgen may terminate the agreement for convenience upon one year’s prior notice, and we may terminate the agreement if Amgen challenges any of our intellectual property relating to the agreement.

Pfizer

In March 2013, we entered into a research, option and license agreement with Pfizer, pursuant to which we granted to Pfizer two options to obtain an exclusive worldwide license to use, develop, manufacture and commercialize Accurins incorporating specified Pfizer drug candidates, for the treatment, prevention and/or diagnosis of any disease or medical condition in humans, except that the licensed rights exclude some vaccine products and products for the treatment of brain cancer. Pfizer may exercise either one or both of its options to acquire the exclusive license for the specified drug candidate during a period of approximately 30 months, beginning on the effective date of the agreement and subject to certain adjustments, by paying us a specified option exercise fee.

We and Pfizer are each responsible for using commercially reasonable efforts to develop licensed products under a development plan. Pfizer is required to pay for all of our development costs. If Pfizer exercises any option, it will be solely responsible for all further development and commercialization activities with respect to the licensed products covered by the option, and is also solely responsible for obtaining all regulatory approvals for the applicable licensed products and conducting all communications with regulatory authorities. Pfizer must use commercially reasonable efforts to develop and seek regulatory approval for at least one licensed product in at least one indication in at least one major market country, and to commercialize each licensed product in each major market country where Pfizer receives regulatory approval. If Pfizer exercises its option with respect to any compound family, we may not develop or commercialize, or license a third party to develop or commercialize, any nanotherapeutic incorporating any compound in such compound family.

We are responsible for manufacturing licensed compounds through early clinical trials. Thereafter, we will negotiate with Pfizer the manufacture of licensed compounds by us for further development and commercialization, but under some circumstances, Pfizer assumes responsibility for all further manufacturing of licensed products.

Under the agreement, we received an upfront payment of $4.0 million and have the potential to receive contingent payments totaling up to $89.5 million in the aggregate under each option upon exercise of the option and achievement by Pfizer of specified development and regulatory events, plus additional contingent payments totaling up to $110 million in the aggregate under each option upon achievement by Pfizer of specified commercial events. We will also receive royalties in the low-single digit to the high-single digit percentages of aggregate worldwide net sales of each licensed product. We receive royalties on a country-by-country and licensed product-by-licensed product basis until the later of the expiration of the Pfizer patents covering such licensed product or twelve years after the first commercial sale of such licensed product in such country.

 

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The agreement will remain in effect, on a country-by-country and licensed product-by-licensed product basis, until Pfizer’s obligation to pay us royalties ends, unless Pfizer fails to exercise either option before both options expire or Pfizer fails to timely pay any option exercise fee, in which case the agreement will terminate immediately. Either Pfizer or we may terminate the agreement for the other party’s uncured material breach or insolvency, and Pfizer may terminate the agreement for convenience upon 60 days’ prior notice.

AstraZeneca

In April 2013, we entered into a license agreement with AstraZeneca, pursuant to which we granted to AstraZeneca a worldwide license to research, develop, manufacture and commercialize Accurins incorporating a specified AstraZeneca kinase inhibitor for any therapeutic use in humans or animals. This license is exclusive with respect to our intellectual property rights that arise under this agreement or the feasibility study that preceded it, and non-exclusive with respect to all of our other intellectual property rights.

We and AstraZeneca are each responsible for using commercially reasonable efforts to develop licensed products under a development plan that extends a previously completed feasibility study we conducted for AstraZeneca. AstraZeneca is required to pay for all of our development costs. AstraZeneca is also solely responsible for, and must use commercially reasonable efforts in, obtaining all regulatory approvals for licensed products. We are responsible for manufacturing licensed product for use in preclinical and some clinical trials. AstraZeneca is responsible for manufacturing other supplies of licensed products. For a specified number of years after entering into this agreement, we may not develop or commercialize a compound against the same target as AstraZeneca’s kinase inhibitor.

Under the agreement, we received an upfront payment of $4.0 million and have the potential to receive contingent payments totaling up to $193 million in the aggregate upon achievement by AstraZeneca of specified clinical, regulatory and commercial events. We will also receive tiered royalties in the low-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed product. We will receive royalties on a country-by-country and licensed product-by-licensed product basis generally until the AstraZeneca patents and any regulatory exclusivity relating to such licensed product expire.

The agreement will remain in effect, on a country-by-country and licensed product-by-licensed product basis, until AstraZeneca’s obligation to pay us royalties ends. Either AstraZeneca or we may terminate the agreement for the other party’s uncured material breach or insolvency, AstraZeneca may terminate the agreement for convenience upon three or six months’ prior notice, depending on the development stage at which such notice is given, or if we undergo a change of control and AstraZeneca does not receive adequate assurances that our acquirer will commit sufficient resources to our development obligations, and we may terminate the agreement if AstraZeneca challenges any of the patents licensed by us to AstraZeneca under the agreement.

Manufacturing

We have a pilot manufacturing facility at our Cambridge location where we conduct process development, scale-up activities and assemble the manufacturing equipment in a non-GMP environment. We do not own or operate GMP manufacturing facilities for the production of any of our drug candidates, and we do not have plans to develop our own manufacturing operations in the foreseeable future. We currently rely on third-party contract manufacturers for all of our required raw materials, therapeutic payload and finished product for our preclinical research and clinical trials. We do not have long-term agreements with any of these third parties. We also do not have any current contractual relationship for the manufacture of commercial supplies of any of our drug candidates if they are approved. If any of our products are approved by any regulatory agency, we intend to enter into agreements with a third-party contract manufacturer and one or more backup manufacturers for the commercial production of those products. Development and commercial quantities of any products that we develop will need to be manufactured in facilities, and by processes, that comply with the requirements of the FDA and the regulatory agencies of other jurisdictions in which we are seeking approval. We currently employ internal resources to manage our manufacturing contractors.

 

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Intellectual Property

Patents and Proprietary Rights

We actively seek to protect our medicinal nanoengineering platform technology, which we consider important to our business, including by pursuing patents relating to our products and compositions, their methods of use and the processes for their manufacture, as well as any other relevant inventions and improvements that are commercially important to the development of our business and are eligible for patent protection. We attempt a layered approach by seeking multiple different patents or patent applications on different aspects of Accurins. We also rely on trade secrets that may be important to the development of our business.

Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for the technology, inventions and improvements we consider important to our business; defend our patents; preserve the confidentiality of our trade secrets; and operate without infringing the patents and proprietary rights of third parties. We also rely on know-how, continuing technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

Medicinal Nanoengineering Platform Patent Portfolio

As of July 31, 2013, we owned nine issued U.S. patents, one patent issued in Europe, as well as 45 pending U.S. provisional and non-provisional patent applications that relate to our medicinal nanoengineering platform, as well as pending foreign counterparts to many of these patents and patent applications. As of July 31, 2013, we had licenses to six U.S. patents and six pending patent applications, as well as several pending foreign counterparts to many of these patents and patent applications that also relate to our medicinal nanoengineering platform. Of these licensed patents and patent applications, we license the majority on an exclusive basis, with the rest licensed non-exclusively to us. The exclusive licenses are, in some cases, limited to certain technical fields, for example for medical and diagnostic purposes. Our owned and licensed patents and patent applications relate to our nanoparticles, nanoparticle compositions, nanoparticles with specific drugs, targeting ligands, methods of making nanoparticles, methods of making targeting ligands and methods of treating breast and prostate cancer using our nanoparticles. We believe these patents and patent applications relate to advances in the nanoparticle field that are important for the development of a therapeutic nanoparticle. The issued patents generally are expected to expire between 2025 and 2030.

BIND-014 Patent Portfolio

We also strive to protect BIND-014 with multiple layers of patents. As of July 31, 2013, of the owned medicinal nanoengineering platform, patents and patent applications described above, five issued U.S. patents, one issued European patent, 16 pending U.S. provisional and various non-provisional patent applications and pending foreign counterparts relate to our BIND-014 Accurin. As of July 31, 2013, of the licensed medicinal nanoengineering platform patents and patent applications described above, to three U.S. patents and three pending patent applications, as well as several foreign counterparts to many of these patents and patent applications relate to our BIND-014 Accurin. Our BIND-014 patent portfolio consists of patents directed to BIND-14 nanoparticles, compositions of BIND-014 nanoparticles, methods of making BIND-014, and methods of using BIND-014. The issued patents directed to BIND-014 generally are expected to expire between 2025 and 2030, and applications are pending which would expire, if issued, between 2032 and 2034.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the date of filing the non-provisional application or PCT application.

In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent. The patent term of a patent that covers

 

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an approved drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the development and regulatory review process. To obtain a patent extension in the United States, the term of the relevant patent must not have expired before the extension application, the patent cannot have been extended previously under this law, an application for extension must be submitted, the product must be subject to regulatory review prior to its commercialization, and the permission for the commercial marketing or use of the product after such regulatory review period is the first permitted commercial marketing or use of the product. The active ingredient in BIND-014, docetaxel, has been previously approved and commercially marketed and, as such, we do not expect to be eligible for a patent term extension in the United States. If our future products contain active ingredients which have not been previously approved, we may be eligible for a patent term extension in the United States. If patent extensions are available to us outside of the United States, we would expect to file for a patent term extension in applicable jurisdictions.

Trade Secrets

We endeavor to maintain trade secret protection for certain aspects of our technology. In some situations, maintaining information as a trade secret is more appropriate than filing a patent application. Specifically, we have a number of trade secrets relating to identifying new Accurins and to our Accurin manufacturing process. With regard to manufacturing Accurins, we believe that small changes in processing Accurins can result in Accurins with different properties. As a result, we expect the FDA and other regulatory bodies to require additional clinical data for approval of a generic Accurin. As such, we believe that maintaining our manufacturing process as a trade secret will be helpful to maintaining our product exclusivity.

Third-Party Rights

Many pharmaceutical companies, biotechnology companies and academic institutions are competing with us in the field of nanotechnology and filing patent applications potentially relevant to our business. In order to contend with the strong possibility of third-party intellectual property conflicts, we periodically conduct freedom-to-operate studies, but such studies may not uncover all patents relevant to our business. With respect to BIND-014, we are aware of a third-party U.S. patent application that contains claims related to a formulation of a nanoparticle composition. We have an issued U.S. patent and pending non-U.S. patent applications claiming similar subject matter, which we believe have earlier priority filing dates than the third party application. Most countries award patents to the first party to file their patent application, however, these U.S. patents and patent applications are subject to U.S. laws that award patents to the first party to invent the claimed invention, rather than the first party to file a patent application. The possibility therefore exists for an interference proceeding between our issued patent and this third-party patent application to determine the earliest party to invent the composition. While we believe we are in a strong position to win any potential interference proceeding, although we believe it unlikely, the possibility exists that this third-party patent application could win such an interference proceeding and obtain claims that cover a formulation of a composition of BIND-014. We believe the potential exists, if necessary, to find and use an alternative formulation which would be outside of any valid and issued claims that could be obtained from this third-party patent application, but we may need to overcome certain technical challenges in order to do so, and this process may cause us to incur additional costs and delays.

From time to time, we find it necessary or prudent to obtain licenses from third-party intellectual property holders. Where licenses are readily available at reasonable cost, such licenses are considered a normal cost of doing business. In other instances, however, we may use the results of freedom-to-operate studies to guide our early-stage research away from areas where we are likely to encounter obstacles in the form of third-party intellectual property. For example, where a third party holds relevant intellectual property and is a direct competitor, a license might not be available on commercially reasonable terms or available at all. We strive to identify potential third-party intellectual property issues in the early stages of research of our research programs, in order to minimize the cost and disruption of resolving such issues.

In spite of these efforts to avoid obstacles and disruptions arising from third-party intellectual property, it is impossible to establish with certainty that our technology platform or our product programs will be free of claims

 

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by third-party intellectual property holders. Even with modern databases and on-line search engines, freedom-to-operate searches are imperfect and may fail to identify relevant patents and published applications. Even when a third-party patent is identified, we may conclude upon a thorough analysis, that we do not infringe the patent or that the patent is invalid. If the third-party patent owner disagrees with our conclusion and we continue with the business activity in question, we might have patent litigation thrust upon us. Alternatively, we might decide to initiate litigation in an attempt to have a court declare the third-party patent invalid or non-infringed by our activity. In either scenario, patent litigation typically is costly and time-consuming, and the outcome is uncertain. The outcome of patent litigation is subject to uncertainties that cannot be quantified in advance, for example, the credibility of expert witnesses who may disagree on technical interpretation of scientific data. Ultimately, in the case of an adverse outcome in litigation, we could be prevented from commercializing a product or using certain aspects of our technology platform as a result of patent infringement claims asserted against us. This could have a material adverse effect on our business. For further discussion of the risks relating to intellectual property see “Risk Factors—Risks Related to Our Intellectual Property.”

In-Licensed Intellectual Property

Massachusetts Institute of Technology

In June 2007, we entered into a license agreement with the Massachusetts Institute of Technology, or MIT, which was amended in November 2008 and April 2013. Pursuant to this agreement, MIT granted us a worldwide license under certain periods and patent applications generally relating to targeted nanoparticles and methods of making targeted nanoparticles to develop and commercialize licensed products and processes for all therapeutic and diagnostic uses and as research reagents, except in connection with therapeutic or prophylactic vaccines with a limited-term option to license certain improvements. Certain licensed MIT patents and patent applications relate to BIND-014. This license is exclusive with respect to certain of MIT’s patent rights and non-exclusive with respect to other of MIT’s patent rights.

We are obligated to use diligent efforts to develop and commercialize one or more licensed products, and thereafter make licensed products reasonably available to the public. We must also achieve specified milestone events by specified dates. Failure to achieve such milestone events may be treated by MIT as a material breach, which could allow MIT to terminate the agreement.

We issued to MIT and certain other parties an aggregate of 130,386 shares of our common stock as an upfront payment, and are responsible for paying MIT an annual license maintenance fee, which is creditable against our royalty obligations. The minimum annual license maintenance fees are $35,000 in 2013, $50,000 per year until the first commercial sale of product, and $75,000 per year after the first commercial sale of product. We must also make contingent payments to MIT totaling up to $1.5 million in the aggregate upon achievement by us or our collaboration partners of specified clinical, regulatory and commercial events. We must also pay MIT royalties in the low-single digit percentages on aggregate worldwide net sales of licensed products, including sales by our collaboration partners. We must also reimburse MIT for all reasonable costs related to the prosecution and maintenance of the licensed patents rights. Under the agreement, we must pay MIT a percentage, ranging from the high-single digits to the low-mid double digits, of any consideration we receive from sublicensees, including our collaboration partners, and a specified percentage, in the mid-single digits, of all payments we receive in excess of a specified amount in the aggregate for the practice of the licensed patents on behalf of non-sublicensee third parties. Finally, in connection with the agreement we issued to MIT and some other parties shares of our common stock representing a low-single digit percentage of our then-outstanding common stock.

The agreement remains in effect until expiration or abandonment of all issued patents and filed patent applications within the rights licensed to us under the agreement. The agreement will terminate automatically if we assign the agreement or any of our rights or obligations thereunder in connection with a change of control and the proposed assignee fails to agree in writing to be bound by the terms and conditions of the agreement. MIT may terminate the agreement if we cease to carry on our business related to the agreement, if we fail to maintain

 

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the insurance coverage required under the agreement or if we materially breach the agreement and fail to cure such breach. We may terminate the agreement for convenience upon six months’ prior notice.

The Johns Hopkins University

In February 2009, we entered into a license agreement with The Johns Hopkins University, or JHU, which was amended in January 2013. Pursuant to the agreement, JHU granted us an exclusive, worldwide license under some of its intellectual property rights relating to nanoparticles targeting PSMA in all fields of use. Certain licensed JHU patent applications relate to BIND-014. Under this agreement, we are obligated to use commercially reasonable efforts to develop and commercialize licensed products as soon as practicable, and after commercialization we must endeavor to keep licensed products reasonably available to the public.

We paid to JHU an upfront payment of $30,000, along with a reimbursement to JHU for patent prosecution and maintenance costs incurred prior to the date of the agreement. We are also responsible for costs relating to the prosecution and maintenance of the licensed patents incurred after the date of the agreement. We must make contingent payments to JHU totaling up to $1 million in the aggregate upon achievement by us or our collaborators of specified patent prosecution, clinical, regulatory and commercial events and pay JHU royalties in the low-single digit percentages on aggregate worldwide net sales of licensed products, including sales by our collaborators, subject to a minimum annual royalty. The current minimum annual royalty payable by us is $5,000, with such amount increasing to $60,000 on the seventh anniversary of the agreement and increasing an additional $10,000 annually thereafter. Finally, we must pay JHU 30% of any consideration we receive from sublicensees who solely sublicense the intellectual property we have licensed from JHU.

The agreement remains in effect on a country-by-country basis until the date of expiration of the last to expire licensed patent in such country. Either we or JHU may terminate the agreement for the other party’s uncured material breach, and we may terminate the agreement for convenience upon 90 days’ prior notice.

Yale University

In January 2013, we entered into a license agreement with Yale University, or Yale, pursuant to which Yale granted us an exclusive, worldwide license under specified intellectual property rights relating to targeted and high density drug-loaded polymeric materials to develop and commercialize licensed products and to practice licensed methods for the treatment of cancer. The rights granted to us under the agreement specifically exclude the use of licensed products for the treatment of brain cancer and for specified types of vaccines. We have the option to expand the rights granted to us under the agreement to include the treatment of cardiovascular disease, inflammation and/or autoimmune disorders, after we initiate specified studies in the respective field, subject to any then-existing third-party rights and upon the payment by us to Yale of a specified amount for each such field so added. Certain of the Yale licensed intellectual property relates to BIND-014.

We are obligated to use commercially reasonable efforts to develop and commercialize one or more licensed products or licensed methods. Our agreement with Yale requires us to achieve specified milestone events. Failure to achieve such milestone events or to use commercially reasonable efforts to develop and commercialize one or more licensed products or licensed methods may result in termination of the agreement by Yale. Both Yale and we must use commercially reasonable efforts, when possible under good business practice, to facilitate the availability of licensed products in low and lower-middle income countries at locally affordable prices, under reasonable terms and circumstances to improve access to such licensed products in such countries.

We paid to Yale an upfront payment of $25,000 and are responsible for paying Yale an annual license maintenance fee in varying amounts (ranging from $10,000 to $100,000) totaling $495,000 over the next ten years, which is creditable against our royalty obligations, and for making contingent payments to Yale totaling up to $260,000 in the aggregate for each licensed product upon achievement by us or our collaborators of specified clinical and regulatory events. While the agreement remains in effect, we must pay Yale royalties below one

 

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percent on aggregate worldwide net sales of licensed products and licensed methods, including sales by our collaborators. Under the agreement, in addition to the royalties described in the previous sentence, we must pay Yale 40% of any consideration we receive from sublicensees who solely sublicense the intellectual property we have licensed from Yale. Finally, we are also responsible for costs relating to the prosecution and maintenance of the licensed patents.

The agreement remains in effect until the date on which the last claim of the licensed patents expires. Either we or Yale may terminate the agreement for the other party’s uncured material breach, we may terminate the agreement for convenience upon 60 days’ prior notice, and Yale may terminate the agreement if we fail to make a payment when due, fail to obtain or maintain adequate insurance coverage, become insolvent, challenge or assist others in challenging the licensed patents, or fail to terminate a sublicense if the applicable sublicensee challenges or assists others in challenging the licensed patents.

Other

We may license intellectual property from certain other parties that we believe to be necessary or useful for the conduct of our business, and may enter additional license agreements in the future.

Intellectual Property in Collaborations

In 2013, we entered into collaboration agreements with Amgen, Pfizer and AstraZeneca. In each collaboration, we provide our collaborator with exclusive rights to inventions relating to the collaborator’s molecules that arise out of the collaboration. These agreements provide for us to own general improvements to our medicinal nanoengineering platform technology that arise out of the collaborations. We did not provide any of our collaborators with the right to enforce our medicinal nanoengineering platform patent portfolio, with the exception of patents relating to the applicable drug candidates.

Competition

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. While we believe that our medicinal nanoengineering technologies, integrated research, clinical and manufacturing capabilities, development experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions. Any drug candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

The key competitive factors affecting the success of BIND-014 and any other drug candidates that we develop, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

 

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Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. Generic products are currently on the market, including the therapeutics payload in BIND-014, docetaxel, for the indications that we are pursuing, and additional products are expected to become available on a generic basis over the coming years. If our drug candidates achieve marketing approval, we expect that they will be priced at a significant premium over competitive generic products.

The most common methods of treating patients with cancer are surgery, radiation and drug therapy, including chemotherapy and targeted drug therapy. There are a variety of available drug therapies marketed for solid tumors. In many cases, these drugs are administered in combination to enhance efficacy. Some of these drugs are branded and subject to patent protection, and others are available on a generic basis, including the therapeutic payload contained in BIND-014. Many of these approved drugs are well established therapies and are widely accepted by physicians, patients and third-party payors. In general, although there has been considerable progress over the past few decades in the treatment of solid tumors and the currently marketed therapies provide benefits to many patients, these therapies all are limited to some extent in their efficacy and frequency of adverse events, and none of them are successful in treating all patients. As a result, the level of morbidity and mortality from solid tumor cancers remains high.

There are also a number of products in late stage clinical development to treat solid tumors. These products in development may provide efficacy, safety, convenience and other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for BIND-014 or any other drug candidate for which we obtain marketing approval.

Specifically, current second-line treatments for NSCLC include docetaxel and other chemotherapy agents such as gemcitabine and vinorelbine, as well as molecularly-targeted therapies such as erlotinib and gefitinib, which are used to treat patients with mutations in the EGFR, and crizotinib, which is used in the small subset of patients that have a mutation in ALK. In addition, two monoclonal antibodies, Bristol-Myers Squibb’s nivolumab that targets PD-1, and F. Hoffmann-La Roche Ltd’s MPDL3280A that targets PD-L1, are currently in Phase 2 clinical trials for NSCLC. Both are immunomodulators that block the activation of programmed cell death receptor. In mCRPC, in addition to first-line chemotherapy agents such as docetaxel, the treatment paradigm is evolving to include use of hormonal therapies such as abiraterone and enzalutamide prior to the administration of chemotherapies, which therapies are currently mainly used in the post-chemotherapy setting. Other similar drugs are also being developed. Cabazitaxel (marketed as Jevtana), a second-line taxane chemotherapeutic, is also being tested in clinical studies against docetaxel for efficacy in mCRPC. In addition, other companies are developing therapies targeting PSMA to treat mCRPC, including an ADC by Progenics Pharmaceuticals, Inc. and a Bispecific T Cell Engager (BITE) antibody by Bayer Healthcare under a collaboration. We also face competition from other nanomedicine platforms developing targeted therapies, including platforms focused on albumin nanoparticles, liposomes and polymeric nanoparticles.

Government Regulation

Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of drug products such as those we are developing. BIND-014 and any other drug candidates that we develop must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

 

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United States Drug Development Process

In the United States, the FDA regulates drugs under the FDCA and FDA’s implementing regulations. Drugs are also subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and subsequent compliance with appropriate federal, state and local statutes and regulations require 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 after approval may subject an applicant to administrative or judicial sanctions. FDA sanctions may include, among other actions, refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us. The process required by the FDA before a drug may be marketed in the United States generally involves the following:

 

   

Completion of extensive preclinical laboratory tests, preclinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s GLP regulations;

 

   

Submission to the FDA of an IND, which must become effective before human clinical trials may begin;

 

   

Performance of adequate and well-controlled human clinical trials in accordance with applicable regulations, including the FDA’s current good clinical practice, or GCP, regulations to establish the safety and efficacy of the proposed drug for its proposed indication;

 

   

Submission to the FDA of a NDA, for a new drug product;

 

   

A determination by the FDA within 60 days of its receipt of an NDA to accept the NDA for filing and review;

 

   

Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the drug is produced to assess compliance with the FDA’s cGMP regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

 

   

Potential FDA audit of the preclinical and/or clinical trial sites that generated the data in support of the NDA; and

 

   

FDA review and approval of the NDA prior to any commercial marketing or sale of the drug in the United States.

Before testing any compounds with potential therapeutic value in humans, the drug candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the drug candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs. The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. An IND is a request for authorization from the FDA to administer an investigational drug product to humans. The central focus of an IND submission is on the general investigational plan and the protocols for human studies. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials and places the IND on clinical hold within that 30-day time period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose a clinical hold on a drug candidate at any time before or during clinical trials due to safety concerns or noncompliance. Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate such trial.

Clinical trials involve the administration of the drug candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed consent

 

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for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND. Further, each clinical trial must be reviewed and approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and rights of trial participants and considers issues such as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

 

   

Phase 1. The drug is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion, the side effects associated with increasing doses, and if possible, to gain early evidence of effectiveness. 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, the initial human testing is often conducted in patients.

 

   

Phase 2. The drug is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases or conditions and to determine dosage tolerance, optimal dosage and dosing schedule.

 

   

Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall benefit/risk ratio of the product and provide an adequate basis for product approval. Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA. Phase 3 clinical trials usually involve several hundred to several thousand participants.

Post-approval studies, or Phase 4 clinical trials, may be conducted after initial marketing approval. These studies are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, FDA may mandate the performance of Phase 4 studies.

The FDCA permits the FDA and an IND sponsor to agree in writing on the design and size of clinical studies intended to form the primary basis of a claim of effectiveness in an NDA. This process is known as a Special Protocol Assessment, or SPA. An SPA agreement may not be changed by the sponsor or the FDA after the trial begins except with the written agreement of the sponsor and the FDA, or if the FDA determines that a substantial scientific issue essential to determining the safety or effectiveness of the drug was identified after the testing began. For certain types of protocols, including carcinogenicity protocols, stability protocols, and Phase 3 protocols for clinical trials that will form the primary basis of an efficacy claim, the FDA has agreed under its performance goals associated with the Prescription Drug User Fee Act, or PDUFA, to provide a written response on most protocols within 45 days of receipt. However, the FDA does not always meet its PDUFA goals, and additional FDA questions and resolution of issues leading up to an SPA agreement may result in the overall SPA process being much longer, if an agreement is reached at all.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a significant risk for human subjects. Phase 1, Phase 2 and Phase 3 clinical trials may fail to be completed successfully within any specified period, if at all. The FDA, the IRB or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

 

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Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or not a trial may move forward at designated checkpoints based on access to certain data from the study. We may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug candidate and, among other things, must include developed methods for testing the identity, strength, quality and purity of the final drug. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration over its shelf life.

FDA Review and Approval Processes

The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. The application must include negative or ambiguous results of preclinical and clinical trials as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the investigational drug product to the satisfaction of the FDA. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.

In addition, under the Pediatric Research Equity Act, or PREA, an NDA or supplement to an NDA must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of data or full or partial waivers. Unless otherwise required by regulation, PREA does not apply to any drug for an indication for which orphan designation has been granted. However, if only one indication for a product has orphan designation, a pediatric assessment may still be required for any applications to market that same product for the non-orphan indication(s).

The FDA reviews all NDAs submitted before it accepts them for filing and may request additional information rather than accepting an NDA for filing. The FDA must make a decision on accepting an NDA for filing within 60 days of receipt. Once the submission is accepted for filing, the FDA begins an in-depth review of the NDA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months from the 60-day filing date in which to complete its initial review of a standard NDA and respond to the applicant, and 6 months for a priority NDA. The FDA does not always meet its PDUFA goal dates for standard and priority NDAs, and the review process is often significantly extended by FDA requests for additional information or clarification.

The FDA reviews each NDA to determine, among other things, whether the proposed product is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength, quality and purity. The FDA may refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to

 

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whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an NDA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical sites to assure compliance with GCP requirements. After the FDA evaluates the application, manufacturing process and manufacturing facilities, it may issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter usually describes all of the specific deficiencies in the NDA identified by the FDA. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s), and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. If a Complete Response Letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling or may condition the approval of the NDA on other changes to the proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-market studies or clinical trials. For example, the FDA may require Phase 4 testing which involves clinical trials designed to further assess a drug safety and effectiveness and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized. The FDA may also determine that a risk evaluation and mitigation strategy, or REMS, is necessary to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS, and the FDA will not approve the NDA without an approved REMS, if required. Depending on FDA’s evaluation of a drug’s risks, a REMS may include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution requirements, patient registries and other risk minimization tools. Following approval of an NDA with a REMS, the sponsor is responsible for marketing the drug in compliance with the REMS and must submit periodic REMS assessments to the FDA.

Section 505(b)(2) Regulatory Pathway

New drugs must obtain FDA approval through an NDA prior to marketing in the United States. Most NDAs are submitted under Section 505(b)(1) of the FDCA, where all clinical investigations supporting the safety and effectiveness of the drug product are conducted by or for the applicant. However, an NDA may also be submitted under Section 505(b)(2) of the FDCA, which enables the applicant to rely, in part, on the FDA’s findings of safety and efficacy for an existing product, or published literature, in support of its application. We plan to seek approval for BIND-014 under Section 505(b)(2) of the FDCA.

Section 505(b)(2) NDAs often provide an alternate regulatory pathway to FDA approval for new or improved formulations or new uses of previously approved products. Specifically, Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. The applicant may rely upon the FDA’s findings from preclinical or clinical studies conducted for an approved product. The FDA may also require Section 505(b)(2) applicants to perform additional studies or measurements to support the change

 

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from the approved product. The FDA may then approve the new drug candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of a generic drug or a new drug submitted for approval under a Section 505(b)(2) NDA. To the extent that the Section 505(b)(2) applicant is relying on findings of safety or efficacy for an already approved product, the applicant is subject to existing exclusivity for the reference product and is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that a generic applicant would. Specifically, applicants must certify to the FDA concerning any patents listed for the approved product in the Orange Book that: (1) the required patent information has not been filed; (2) the listed patent has expired; (3) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or (4) the listed patent is invalid or will not be infringed by the new product. A certification that the new product will not infringe the already approved product’s listed patents or that such patents are invalid is called a Paragraph IV certification. If an applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification prevents the FDA from approving the application until the earlier of 30 months from the date of the lawsuit, expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the applicant. Thus approval of a Section 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of a new chemical entity, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making a drug product available in the United States for this type of disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting an NDA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity. The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding toward clinical trial costs, tax advantages and user-fee waivers. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval of the same drug or biological product as defined by the FDA or if our drug candidate is determined to be contained within the competitor’s product for the same indication or disease. If a

 

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drug product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity. Orphan drug status in the EU has similar but not identical benefits in that jurisdiction.

Expedited Development and Review Programs

The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new drug products that meet certain criteria. Specifically, new drugs are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. Unique to a Fast Track product, the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

Any product submitted to the FDA for approval, including a product with a Fast Track designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. A product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review in an effort to facilitate the review. Additionally, a product may be eligible for accelerated approval. Drug products studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect