Sarepta Therapeutics
Annual Report 2015

Plain-text annual report

UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549 FORM 10-K (Mark One)xxANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31, 2015OrooTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the transition period from toCommission file number: 001-14895 Sarepta Therapeutics, Inc.(Exact name of registrant as specified in its charter) Delaware 93-0797222(State or other jurisdiction ofincorporation or organization) (I.R.S. EmployerIdentification Number) 215 First StreetSuite 415Cambridge, MA 02142(Address of principal executive offices) (Zip Code)Registrant’s telephone number, including area code: (617) 274-4000Securities registered pursuant to Section 12(b) of the Act: Tile of Each Class Name of Exchange on Which RegisteredCommon Stock, $0.0001 par value The NASDAQ Stock Market LLC(The NASDAQ Global Select Market)Securities registered pursuant to Section 12(g) of the Act:None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes o No xIndicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes o No xIndicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during thepreceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90days. Yes x No oIndicate by check mark whether the registrant has submitted electronically and posted on its corporate Website, if any, every Interactive Data File required to be submittedand posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submitand post such files). Yes x No oIndicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§ 229.405 of this chapter) is not contained herein, and will not becontained, to the best of the registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to thisForm 10-K. xIndicate 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 filerxAccelerated filero Non-accelerated filero (Do not check if a smaller reporting company)Smaller reporting companyoIndicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes o No xThe aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant as of June 30, 2015 was approximately $1,263,325,580.The number of outstanding shares of the registrant’s common stock as of the close of business on February 19, 2016 was 45,666,357. DOCUMENTS INCORPORATED BY REFERENCEThe registrant has incorporated by reference into Part III of this Annual Report on Form 10-K, portions of its definitive Proxy Statement for its 2016 annual meeting to befiled with the Commission no later than 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K. Sarepta Therapeutics, Inc.FORM 10-K INDEX PagePART I 4Item 1. Business 4Item 1A. Risk Factors 20Item 1B. Unresolved Staff Comments 35Item 2. Properties 35Item 3. Legal Proceedings 36Item 4. Mine Safety Disclosures 37PART II 38Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 38Item 6. Selected Financial Data 39Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 40Item 7A. Quantitative and Qualitative Disclosures About Market Risk 53Item 8. Financial Statements and Supplementary Data 54Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure 54Item 9A. Controls and Procedures 54Item 9B. Other Information 57PART III 58Item 10. Directors, Executive Officers and Corporate Governance 58Item 11. Executive Compensation 58Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 58Item 13. Certain Relationships and Related Transactions, and Director Independence 58Item 14. Principal Accounting Fees and Services 58PART IV 59Item 15. Exhibits, Financial Statement Schedules 59 -i-Forward-Looking InformationThis Annual Report on Form 10-K, including the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sectionin Item 7, and other materials accompanying this Annual Report on Form 10-K contain forward-looking statements or incorporate by reference forward-looking statements. The statements contained in this Annual Report on Form 10-K that are not purely historical are forward-looking statements within themeaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-lookingstatements are often identified by words such as “believe,” “anticipate,” “expect,” “intend,” “plan,” “will,” “may,” “estimate,” “could,” “continue,”“ongoing,” “predict,” “potential,” “likely,” “seek” and other similar expressions, as well as variations or negatives of these words. You should read thesestatements carefully because they discuss future expectations, contain projections of future results of operations or financial condition, or state other“forward-looking” information. These statements relate to our future plans, objectives, expectations, intentions and financial performance and theassumptions that underlie these statements. These forward-looking statements include, but are not limited to: ·our expectations regarding the timing of research, development, preclinical and clinical trial results, data and analyses relating to the safetyprofile and potential clinical benefits of our product candidates, including eteplirsen, our phosphorodiamidate morpholino oligomer(“PMO”) chemistries, our other PMO-based chemistries and our other RNA-targeted technologies; ·our expectations regarding the Food and Drug Administration’s (“FDA”) interpretation of our data and information on our productcandidates, PMO and PMO-based chemistries and RNA-targeted technologies and the impact of the FDA’s interpretations on our FDAsubmissions (including our investigational new drug applications (“INDs”) and new drug applications (“NDAs”)), filing decisions by theFDA, potential advisory committee meeting dates and advisory committee recommendations, and FDA product approval decisions and relatedtimelines; ·our estimates regarding how long our currently available cash, cash equivalents and investments will be sufficient to finance our operationsand business plans and statements about our future capital needs; ·our current and planned investment in and activities in preparation for a potential commercial launch of eteplirsen, including continuing tonegotiate and enter into commercial and supply contracts, scaling up manufacturing and hiring commercial positions and the impact ofwinding down or terminating these commitments if the FDA does not approve our eteplirsen NDA; ·our ability to raise additional funds to support our business plans and the impact of our credit and security agreement with MidCapFinancial on our financial condition and future operations; ·our expectations regarding our ability to become a leading developer and marketer of PMO-based and RNA-targeted therapeutics andcommercial viability of our product candidates, chemistries and technologies; ·the potential safety, efficacy, potency and utility of our product candidates, chemistries and technologies in the treatment of Duchennemuscular dystrophy (“DMD”) and in rare, infectious and other diseases; ·our expectations regarding the timing, completion and receipt of results from our ongoing development programs for our pipeline of productcandidates including their potential consistency with prior results; ·our ability to effectively manage the clinical trial process for our product candidates on a timely basis, including our ability to conduct aplacebo-controlled confirmatory study for eteplirsen in the U.S. using an exon 53-skipping product candidate; ·our expectations regarding our ability to engage a number of manufacturers with sufficient capability and capacity to meet ourmanufacturing needs, including with respect to the manufacture of subunits, drug substance (“APIs”) and drug product, within the timeframes and quantities needed to provide our product candidates, including eteplirsen, to patients in larger scale clinical trials or in potentialcommercial quantities, and meet regulatory and Company quality control requirements; ·the impact of regulations as well as regulatory decisions by the FDA and other regulatory agencies on our business, including with respect toour eteplirsen NDA submission as well as the development of our product candidates and our financial and contractual obligations; ·our expectations regarding the potential markets for our product candidates; ·our expectations regarding our manufacturing and scale-up techniques and our ability to synthesize and purify our product candidates toadequately support clinical development and potential commercialization; ·the potential acceptance of our product candidates, if introduced, in the marketplace; ·the possible impact of competing products on our product candidates and our ability to compete against such products;-1- ·the impact of potential difficulties in product development, manufacturing, or the commercialization of our product candidates, includingdifficulties in establishing the commercial infrastructure necessary for the commercialization of eteplirsen; ·our expectations regarding partnering opportunities and other strategic transactions; ·the extent of protection that our patents provide and our pending patent applications may provide, if patents issue from such applications, toour technologies and programs; ·our plans and ability to file and progress to issue additional patent applications to enhance and protect our new and existing technologiesand programs; ·our ability to invalidate some or all of the claims of patents issued to competitors and pending patent applications if issued to competitors,and the potential impact of those claims on the potential commercialization of our product candidates; ·our ability to successfully challenge the patent positions of our competitors and successfully defend our patent positions in the actions thatthe United States Patent and Trademark Office (“USPTO”) may take or has taken with respect to our patent claims or those of third parties,including with respect to interferences that have been declared between our patents and patent applications held by BioMarinPharmaceuticals, Inc., relating to eteplirsen and SRP-4053 and our expectations regarding the impact of these interferences on our businessplans, including our current commercialization plans for eteplirsen and SRP-4053; ·our ability to operate our business without infringing the intellectual property rights of others; ·our ability to enter into contracts, including collaborations or licensing agreements, with respect to our technology and product candidates,with third parties, including government entities; ·our estimates regarding future revenues, research and development expenses, other expenses, capital requirements and payments to thirdparties; ·the timing and outcomes of ongoing interference proceedings and related appeals; ·the impact of litigation on us, including actions brought by stockholders; ·our ability to attract and retain key employees needed to execute our business plans and strategies and our expectations regarding our abilityto manage the impact of any loss of key employees; ·our ability to comply with applicable environmental laws and regulations; ·our expectations relating to potential funding from government and other sources for the development of some of our product candidates; ·the impact of the potential achievement of performance conditions and milestones relating to our restricted stock awards; ·our beliefs and expectations regarding milestone, royalty or other payments that could be due to third parties under existing agreements; and ·our succession plan, including the search for a permanent full-time CEO and the effect that the changes in management could have on theCompany, its business plans and its regulatory and clinical discussions and relationships.All forward-looking statements are based on information available to us on the date of this Annual Report on Form 10-K and we will not update anyof the forward-looking statements after the date of this Annual Report on Form 10-K, except as required by law or the rules and regulations of the U.S.Securities and Exchange Commission.(“SEC”). We caution readers not to place undue reliance on forward-looking statements. Our actual results coulddiffer materially from those discussed in this Annual Report on Form 10-K. The forward-looking statements contained in this Annual Report on Form 10-K,and other written and oral forward-looking statements made by us from time to time, are subject to certain risks and uncertainties that could cause actualresults to differ materially from those anticipated in the forward-looking statements. Applicable risks and uncertainties include, among others, the fact that:the FDA may further delay our PDUF date or may not approve eteplirsen as a DMD therapeutic; we may be delayed or may not be able to comply with theFDA’s requests for additional information in connection with our eteplirsen NDA; the additional information and data we collect for eteplirsen may not beconsistent with prior data or results or may not support a positive advisory committee vote or recommendation relating to our eteplirsen NDA, if any, orapproval of eteplirsen by the FDA; we may be delayed in and may not be able to successfully conduct or obtain positive results in our current and plannedclinical trials for eteplirsen and other product candidates in our pipeline; we may not have sufficient funds to execute on our business plans and strategy;we may not be able to obtain regulatory approvals for our product candidates in a timely manner nor achieve commercial viability; we may not be able toincorporate our PMO and other technology into therapeutic commercial products; we may not be able to successfully navigate the uncertainties related toregulatory processes; we may not be able to demonstrate acceptable levels of safety, efficacy and-2-quality in our product candidates through our preclinical and clinical trials; compliance with environmental laws could have a negative impact on ourbusiness if we are not able to effectively manage our real estate, manufacturing and other Company operations that may deal with hazardous materials; werely on third parties to provide service, including the manufacturing of our product candidates, in connection with our preclinical and clinicaldevelopment programs and commercialization plan and we may not be able to secure the service or quality of service we need from third parties; thepharmaceutical industry is subject to greater government scrutiny and regulation, and we may not be able to respond to changing laws and regulationsaffecting our industry, including any reforms to the regulatory approval process administered by the FDA or changing enforcement practices relatedthereto; we may not be able to obtain and maintain patent protection for our product candidates, preserve our trade secrets or prevent third parties frominfringing on our proprietary rights; we may not be able to capitalize on our executive team’s relationships and expertise to meet our expected timelines forregulatory submissions, clinical development plans and bringing our product candidates to market; we may not be able to hire and retain key personnel orattract qualified personnel, including a permanent full-time CEO; we may not be able to establish and maintain arrangements with third parties who areable to meet manufacturing needs for large-scale clinical trials or potential commercial needs within sufficient timelines or at acceptable costs; competitiveproducts and pricing may have a negative impact on our business; there are uncertainties associated with our future capital needs; we may not be able toraise additional funds to execute our business plans; we may not be able to attract sufficient capital or to enter into strategic relationships; the outcome ofour patent interferences, investigations and litigation and associated damages and expenses is uncertain; and those risks and uncertainties discussed inPart I, Item 1 “Business” and Item 1A “Risk Factors” of this Annual Report on Form 10-K. -3-PART I Item 1. Business.OverviewWe are a biopharmaceutical company focused on the discovery and development of unique RNA-targeted therapeutics for the treatment of rare,infectious and other diseases. Applying our proprietary, highly-differentiated and innovative platform technologies, we are able to target a broad range ofdiseases and disorders through distinct RNA-targeted mechanisms of action. We are primarily focused on rapidly advancing the development of ourpotentially disease-modifying DMD drug candidates, including our lead DMD product candidate, eteplirsen, designed to skip exon 51. On August 25, 2015,we announced the FDA filing of our NDA for eteplirsen for the treatment of DMD amenable to exon 51 skipping. The FDA postponed the AdvisoryCommittee meeting for the review of the eteplirsen NDA previously scheduled for January 22, 2016 due to severe weather. On February 8, 2016, weannounced that the FDA notified us that the Prescription Drug User Fee Act (“PDUFA”) action date for eteplirsen has been extended to May 26, 2016 due toour submission of four-year clinical effectiveness data on January 8, 2016 to the FDA, which the FDA designated as a major amendments to the eteplirsenNDA. We are also developing therapeutics using our technology for the treatment of drug resistant bacteria and infectious, rare and other human diseases.Objectives and Business StrategyWe believe that our highly-differentiated and proprietary RNA-targeted technology platforms can be used to develop novel pharmaceutical productsto treat a broad range of diseases and address key unmet medical needs. We intend to leverage our RNA-targeted technology platforms, organizationalcapabilities and resources to become a leading developer and marketer of RNA-targeted therapeutics, including for the treatment of rare, infectious and otherdiseases, with a diversified portfolio of product candidates. In pursuit of this objective, we intend to engage in the following activities: ·advancing the development of eteplirsen and our other drug candidates for the treatment of DMD to realize the product opportunities of suchcandidates and potentially provide significant clinical benefits; ·further explore funding, collaboration and other opportunities to support continued development of our rare, infectious and other research anddevelopment programs; and ·leveraging our RNA-targeted technology platforms to identify product candidates in additional therapeutic areas and explore various strategicopportunities, including potential partnering, licensing or collaboration arrangements with industry partners.Development ProgramsDMD. Our lead program, with a pipeline of ten product candidates, focuses on the development of disease-modifying therapeutic candidates for DMD,a rare genetic muscle-wasting disease caused by the absence of dystrophin, a protein necessary for muscle function. Currently, there are no approved disease-modifying therapies for DMD in the U.S. If we are successful in our development efforts, eteplirsen, our lead DMD product candidate, and our follow-onexon-skipping DMD candidates would address an unmet medical need. We are in the process of conducting several studies with eteplirsen and our follow-onDMD candidates including:Eteplirsen ·Study 4658-US-202 (“Study 202”) – an ongoing U.S. open label extension of our initial Phase IIb clinical trial which was completed in2012, with over four and a half years of data collected as of February 2016 (inclusive of the primary study); ·Study 4658-301/PROMOVI (“Study 301”) – a confirmatory U.S. study, started in 2014, with a treated arm evaluating the safety and efficacy ofeteplirsen in ambulatory DMD patients amenable to exon-51-skipping and an untreated concurrent control arm with patients that are notamenable to exon-51-skipping; ·Study 4658-204 (“Study 204”) – a U.S. study, started in 2014, evaluating the safety and tolerability of eteplirsen in patients with advancedstage DMD; and ·Study 4658-203 (“Study 203”) – a U.S. study, started in 2015, evaluating the safety and tolerability of eteplirsen in patients with early stageDMD. Follow-on Exons ·Study 4053-101 (“SKIP-NMD”) – a European Union (“E.U.”) study we are conducting in collaboration with a consortium of scientific, clinicaland industrial partners in the E.U. Part I of the study, started in 2014, is a dose titration,-4- placebo-controlled study, evaluating the safety, tolerability and pharmacokinetics of SRP-4053. Part II of the study, started in 2015, evaluatesthe safety and efficacy of SRP-4053 in patients with DMD amenable to exon 53 skipping; ·Study 4045-101 – a randomized, double‑blind, placebo‑controlled, dose‑titration study in the U.S., started in 2015, evaluating the safety,tolerability and pharmacokinetics of SRP‑4045 in advanced‑stage patients with DMD amenable to exon 45 skipping, followed by anopen‑label safety and efficacy evaluation.In addition, we are currently working towards starting a second confirmatory study to support eteplirsen approval in 2016, which will evaluate thesafety and efficacy of our product candidates designed to skip exons 45 and 53. We have satisfactorily responded to the FDA’s inquiries on preclinical datafor this study relating our exon-53 product candidate.Infectious Diseases.Anti-virals. The antisense technology platform has been applied to the development of potential therapeutics for Ebola and Marburg hemorrhagicfever and pandemic H1N1 influenza viral infections. Though our original discovery and development contracts from the Department of Defense (“DoD”) areno longer active, we remain active partners with the National Institutes of Health (“NIH”) and the National Institute of Allergy and Infectious Diseases(“NIAID”) for continued development of our influenza product candidate. Following encouraging preclinical results, in February 2012, we announced PhaseI results for the Ebola, Marburg and influenza product candidates which appeared to be well tolerated and showed no drug-associated safety findings in thehuman study subjects. All three product candidates use our PMOplus® technology. We are open to partnership possibilities and other avenues to supportfurther development of these Ebola, Marburg and influenza product candidates; however, if we do not succeed in these efforts, we will likely curtail theirfurther development.Discovery and Research ProgramsOur discovery and research programs include collaborations with various parties and focus on developing therapeutics in rare, genetic, anti-bacterial,neuromuscular and central nervous system diseases. We are exploring the application of our proprietary PMO platform technology in various diseases.Proprietary Manufacturing TechniquesWe believe we have developed proprietary state-of-the-art manufacturing and scale-up techniques that allow synthesis and purification of our productcandidates to support clinical development as well as potential commercialization. We have entered into certain manufacturing and supply arrangementswith third parties which will in part utilize these techniques to support production of certain of our product candidates and their components. We currently donot have any of our own internal mid-to-large scale manufacturing capabilities to support a clinical or commercial supply of our product candidates.General Corporate InformationWe were originally incorporated in the State of Oregon on July 22, 1980 and on June 6, 2013, we reincorporated in the State of Delaware. Ourprincipal executive offices are located at 215 First Street, Suite 415, Cambridge, MA 02142 and our telephone number is (617) 274-4000. On July 12, 2012,our common stock began trading under the symbol “SRPT” on the NASDAQ Global Market on a split-adjusted basis following a one-for-six reverse stocksplit that was effective on July 11, 2012. Our common stock is quoted on the NASDAQ Global Select Market under the same symbol.We have not generated any revenue from product sales to date and there can be no assurance that revenue from product sales will be achieved. Even ifwe do achieve revenue from product sales, we are likely to continue to incur operating losses in the near term. For more information about our revenues andoperating losses, see Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations.As of December 31, 2015, we had approximately $204.0 million of cash, cash equivalents and investments, consisting of $80.3 million of cash andcash equivalents, $112.2 million of short-term investments and $11.5 million of restricted cash and investments. We believe that our balance of cash, cashequivalents and investments is sufficient to fund our current operational plan for at least the next twelve months. In addition to pursuing additional cashresources through public or private financings, we may also seek to enter into contracts, including collaborations or licensing agreements with respect to ourtechnology, with third parties, including government entities.-5-Where You Can Find Additional InformationWe make available free of charge through our corporate website, www.sarepta.com, our annual reports, quarterly reports, current reports, proxystatements and all amendments to those reports as soon as reasonably practicable after such material is electronically filed or furnished with the U.S.Securities and Exchange Commission (“SEC”). These reports may also be obtained without charge by submitting a written request via mail to InvestorRelations, Sarepta Therapeutics, Inc., 215 First Street, Suite 415, Cambridge, MA 02142 or by e-mail to investorrelations@sarepta.com. Our internet websiteand the information contained therein or incorporated therein are not intended to be incorporated into this Annual Report on Form 10-K. In addition, thepublic may read and copy any materials we file or furnish with the SEC, at the SEC’s Public Reference Room at 100 F Street, N.E., Washington, D.C. 20549 ormay obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. Moreover, the SEC maintains an Internet sitethat contains reports, proxy and information statements, and other information regarding reports that we file or furnish electronically with the SEC atwww.sec.gov.We have adopted a Code of Business Conduct and Ethics and written charters for our Audit Committee, Compensation Committee and Nominatingand Corporate Governance Committee. Each of the foregoing is available on our website at www.sarepta.com under “For Investors—CorporateGovernance.” In accordance with SEC rules, we intend to disclose any amendment (other than any technical, administrative, or other non-substantiveamendment) to the above code, or any waiver of any provision thereof with respect to any of the executive officers, on our website within four business daysfollowing such amendment or waiver. In addition, we may use our website as a means of disclosing material non-public information and for complying withour disclosure obligations under Regulation Fair Disclosure promulgated by the SEC. These disclosures will be included on our website under the “ForInvestors” section.Lead Development Program: Pipeline of Exon-Skipping PMO Product Candidates for Duchenne Muscular DystrophyDMD BackgroundDMD is one of the most common fatal genetic disorders affecting children (primarily boys) around the world. DMD is a devastating and incurablemuscle-wasting disease associated with specific mutations in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiberfunction. The absence of dystrophin in muscle cells leads to significant cell damage and ultimately causes muscle cell death and fibrotic replacement.Females are rarely affected by the disorder. In the absence of dystrophin protein, affected individuals generally experience: ·muscle damage characterized by inflammation, fibrosis and loss of myofibers beginning at an early age; ·muscle weakness and progressive loss of muscle function beginning in the first few years of life; ·decline of ambulation and respiratory function after the age of seven; ·total loss of ambulation in the pre-teenage or early teenage years; ·progressive loss of upper extremity function during mid- to late-teens; and ·respiratory and/or cardiac failure in their 20s to which they typically succumb.There is currently no approved disease modifying treatment or cure for DMD in the U.S. The yearly cost of care for individuals with DMD is high andincreases with disease progression. Although DMD is a rare disease, we believe it represents a substantial product opportunity due to the severity andinexorable progression of the symptoms.-6-Exon-Skipping PipelineThe table below summarizes our DMD studies including the confirmatory trials we initiated in 2015 and our planned clinical trials: Exon TargetTreatment Study Duration(weeks) U.S./E.U. Number ofPatients Status DMD PopulationExon 51 AVI-4658-33 Single Dose EU 7 Completed 10-17 yrs, non-amb(b)Exon 51 AVI-4658-28 12 EU 19 Completed 5-15 yrs, ambExon 51 4658-US-201 28 US 12 Completed 7-13 yrs, ambExon 51 4658-US-202 (a) 268 US 12 Dosing/Enrollment closed(Data through 236 weeks) 7-13 yrs, ambExon 51 4658-301 96 US 160 Dosing 7-16 yrs, ambExon 51 4658-204 96 US 24 Dosing/Enrollment closed 7-21 yrs, non-ambExon 51 4658-203 96 US 40 Dosing 4-6 yrs, ambExon 51 4658-102 48 EU/US 12 Planned 6 mos - 4 yrsExon 45 4045-101 120 US 12 Dosing/Enrollment closed 7-21 yrs, non-ambExon 53 4053-101 144 EU 48 Dosing 6-15 yrs, ambExon 45/53 4045-301 48 EU/US 99 Planned 7-16 yrs, amb (a)Weeks presented are inclusive of 28 completed weeks in study 4658-us-201. (b)Amb denotes ambulatoryEteplirsen. Eteplirsen, our lead DMD product candidate, is an antisense PMO therapeutic in Phase III clinical development for the treatment ofindividuals with DMD who have an error in the gene coding for dystrophin that is amenable to skipping exon 51. Eteplirsen targets the most frequent seriesof mutations that cause DMD. Eteplirsen has been granted orphan drug designation in the U.S. and E.U. In 2007, the FDA granted eteplirsen fast track statusand we are continuing to discuss with the FDA the possibility of expedited regulatory programs for eteplirsen.For approximately four years, we have been collecting data on the safety and efficacy of eteplirsen through a Phase llb open label extension study,Study 202. In this study, biopsies were taken from patients at 48 weeks and, using different physicochemical methods on the tissue samples collected, wemeasured increases in novel dystrophin production. In July 2014, we announced that at 144 weeks (i) patients evaluable (n=10) on the 6-minute walk test(“6MWT”) showed a decline in walking ability at a rate slower than would be expected based on available DMD natural history data and (ii) a continuedstabilization of respiratory muscle function was observed, as assessed by pulmonary function tests. In January 2015, we announced that at 168 weeks(i) continued ambulation across all patients evaluable on the 6MWT was observed, however, all patients showed a decline in distance walked on this measuresince the week 144 time point, (ii) stability of respiratory muscle function was observed, as assessed by pulmonary function tests and (iii) good tolerabilityand no clinically significant treatment-related adverse events or serious adverse events were reported. In October 2015, we announced additional clinicalefficacy and safety data that demonstrated that (i) eteplirsen provided a statistically significant advantage of 151 meters in the ability of study participants towalk at three years versus an external DMD control, (ii) eteplirsen-treated patients (n=12) experienced a slower rate of decline through week 192 than externalDMD controls and (iii) the eteplirsen safety profile remained consistent with prior results. After approximately four years of treatment with eteplirsen, resultsof the 6MWT at 216 weeks showed continued ambulation of the 10 evaluable patients. In January 2016, we announced more than four years of data for 11 ofthe 13 external control patients that demonstrated 10 of the 11 patients lost ambulation, a statistically significant difference. Please read Item 7,Management’s Discussion and Analysis of Financial Condition and Results of Operations — Summary and Timeline of Eteplirsen Data Disclosure includedelsewhere in this Annual Report on Form 10-K for more information.On August 25, 2015, we announced the FDA’s filing of our NDA for eteplirsen for the treatment of DMD amenable to exon 51 skipping. Eteplirsen isunder priority review with a current PDUFA action date of May 26, 2016. Please read Overview and Government Regulation for additional information. Additional DMD Product Candidates. In addition to our lead product candidate, eteplirsen, we are pursuing development of additional exon-skippingdrugs, to support our broad-based development program for the treatment of DMD. Our additional nine product candidates target skipping of exons 8, 35, 43,44, 45, 50, 52, 53 and 55 and are at various stages of development.Exon 53. To support certain clinical proof of concept studies and investigational new drug (“IND”) -enabling activities for an exon 53-skippingtherapeutic, we announced in November 2012 that we are collaborating in the SKIP-NMD Consortium with University College London’s scientist, ProfessorFrancesco Muntoni, M.D., the Dubowitz Neuromuscular Centre, the Institute of Child Health and other scientists from the E.U. and the U.S. In connectionwith this collaboration, the Consortium received an E.U. Health Innovation-1 2012 collaborative research grant (grant agreement No. 305370) to supportdevelopment of an exon 53-skipping therapeutic, based on our PMO chemistry. Targeting exon 53 with this technology will potentially address one of themost prevalent-7-sets of mutations in DMD that are amenable to exon-skipping (eg. deletions of exons such as 42-52, 45-52, 47-52, 48-52, 49-52, 50-52, 52 or 54-58). Wecompleted Part I and are currently conducting Part II of a Phase I/IIa clinical trial for an exon 53-skipping product candidate in the E.U.Exon 45. In collaboration with Children’s National Medical Center (“CNMC”) in Washington, D.C. and the Carolinas Medical Center (“CMC”) inCharlotte, N.C., we have developed an exon 45-skipping product candidate. This collaboration is funded primarily through two grants, one from DoD’sCongressionally Directed Medical Research Program to CNMC and the other from the National Institute of Neurological Disorders and Stroke to the CMC.This funding is intended to pursue the most promising treatments for DMD. The collaboration has supported a series of Good Laboratory Practice (“GLP”)toxicology studies for an exon 45-skipping drug candidate based on our PMO chemistry. We have initiated and completed enrollment of a dose-rangingstudy for our exon 45-skipping product candidate in the U.S. (Study 4045-101).Additionally, we are also planning to initiate a placebo-controlled confirmatory study with product candidates designed to skip exons 45 and 53(Study 4045-301).Exons 8, 35, 43, 44, 50, 52 and 55. Selection of lead sequences for product candidates designed to skip each of these exons are underway. Althoughwe were previously collaborating with the NIH for the development of an exon 50 product candidate, we mutually agreed to terminate our CollaborativeResearch and Development Agreement in February 2013 and we are now developing an exon 50 skipping candidate utilizing our own research anddevelopment capabilities.Our DMD program is part of our larger pan-exon strategy for the development of drug candidates to address the most prevalent exon deletions in theDMD population. Because the majority of DMD patients have exon deletions that cluster together, a small number of exon-skipping therapies willpotentially be disease-modifying for a relatively large percentage of DMD patients. Approximately 75-80% of the total DMD population is potentiallytreatable with exon-skipping therapeutics. Development Programs: Infectious DiseasesOur infectious diseases therapeutic programs continue to evolve, and remain based on our translation inhibition through steric hindrance technology.The applications to date have included our proprietary PMOplus® chemistry for post-exposure and therapeutic medical countermeasures to hemorrhagicfever virus infections (including Ebola and Marburg viruses), and for pandemic and seasonal influenza A infection. The contracts funding the hemorrhagicfever virus programs have ended, and while we are no longer actively developing those products, we may consider a collaborative relationship in thefuture. We have an active partnership with the NIAID, an institute within the NIH, for ongoing clinical development of our influenza therapeutic candidate. As previously reported, the Phase I human safety, tolerability and pharmacokinetics single ascending dose trials of the drug candidates for Ebola,Marburg and pandemic influenza A, and the multiple ascending dose trial of the Marburg drug candidate have been completed. The Phase I single ascendingand multiple ascending dose clinical trial of the pandemic influenza drug candidate has now also been completed, and data are being analyzed. These programs were vital to informing us in all aspects of the clinical applications, chemistry and materials development of the proprietaryPMOs. The funding received to support the research and development of these antiviral candidates from the U.S. government represented substantially all ofour revenues during those funding periods. As of December 31, 2014, we had completed all development activities of our contracts with the U.S.government. In 2015, key animal efficacy and human safety and pharmacokinetic data were published in the New England Journal of Medicine,Antimicrobial Agents and Chemotherapy, mBio, Antiviral Research and by the American Society of Microbiology Journals, as well as presented at a numberof national and international scientific and industry conferences.Discovery and Research ProgramsRare Diseases. We are researching the application of our proprietary peptide-conjugated PMO (“PPMO”) technology to regulate progerin protein inprogeria patients and in other diseases.Anti-Bacterials. The rapid emergence of broad antibiotic resistance has underscored the urgent need for new paradigms in antimicrobial development.Our anti-bacterial program is focused on drug-resistant bacteria identified by the Centers for Disease Control and Prevention (“CDC”) as urgent or seriousthreats to the U.S. healthcare system. Early research findings demonstrate that targeted PPMOs can successfully inhibit translation of essential structuralgenes such as acyl carrier protein (“acpP”), resistance proteins such as the NDM-1 metallo-b-lactamase, or those responsible for biofilm formation, which iscritical for Burkholderia cepacia complex to evade host immune responses or systemic antibiotics such as cysteine protease cepI., which is responsible forbiofilm expression. Additionally, though acpP alone can be bactericidal at clinically achievable concentration, data demonstrates that-8-co-administration of the PPMOs targeting NDM-1 can restore antibiotic activity of drugs like meropenem or imipenem to clinically achievable levels inhigh-level multidrug resistant Acinetobacter, E. coli, Klebsiella, and Burkholderia spp in both bench top and mouse models. Finally, we have also seen thatPPMOs targeting structural genes such as acpP or quorum sensing genes such as cepI (responsible for biofilm expression) can penetrate and disruptestablished biofilm; furthermore, the PPMOs targeting acpP can successfully kill the established bacterial colonies in Burkholderia cepacia models. Webelieve the results of this early research could have broad commercial applicability. We are exploring IND enabling studies now, and are open to partnershipopportunities in the development of our anti-bacterial program.Proprietary Platform TechnologyPMO. The original PMO structure and variations of this structure that are so-called PMO-based are central to our proprietary chemistry platform. PMOand PMO-based therapeutics have been safely dosed in over 400 patients. PMO and PMO-based compounds are synthetic compounds that bind tocomplementary sequences of RNA by standard Watson-Crick nucleobase pairing. When targeted to mRNA, PMO and PMO-based compounds downregulateprotein translation by steric blockade. The two key structural differences between PMO/PMO-based compounds and naturally occurring RNA are that thePMO nucleobases are bound to synthetic morpholino rings instead of ribose rings, and the morpholino rings are linked by phosphorodiamidate groupsinstead of phosphodiester groups. Replacement of the negatively charged phosphodiester in RNA with the uncharged phosphorodiamidate group in PMOeliminates linkage ionization at physiological pH. Because of these modifications, PMO and PMO-based compounds are resistant to degradation by plasmaand intracellular enzymes. Unlike the RNA-targeted technologies of siRNAs and DNA gapmers, PMO and PMO-based compounds operate by steric blockaderather than by cellular enzymatic degradation to achieve their biological effects. PMOs thus use a fundamentally different mechanism from these other RNA-targeted technologies.PMO technologies can be used to selectively up-regulate or down-regulate the production of a target protein through pre-mRNA splice alteration. Thismechanism can be used to correct disease-causing genetic errors by inducing the targeted expression of novel proteins. Thus PMO and PMO-basedcompounds can be designed to create more, less, or none of certain proteins, or produce analogues of endogenous proteins.The safety of therapeutic agents is paramount. We believe that our PMO and PMO-based compounds significantly reduce potential for off-targeteffects specifically because of their demonstrated inactivity with key molecular mechanisms that are known to be toxicologically active when stimulated.Additionally, consistent with our research and development to date, we believe that PMO and PMO-based compounds do not exhibit coagulation andimmune stimulatory effects, do not stimulate toll-like receptors (“TLRs”) or receptors of the RIG-I-like receptor family, and do not sequester metal ions awayfrom the catalytic centers of polymerases.In addition to our original PMO technology, we have also developed three new PMO-based chemistry platforms. We believe that the novelcharacteristics intrinsic to these new platforms will allow for the development of drug candidates with excellent safety and efficacy.PPMO. The first of these novel chemistries is based on cell-penetrating PPMOs. Cellular uptake, potency, efficacy, and specificity of tissue targetingmay be significantly enhanced.PMOplus®. The second of these chemistries, PMOplus®, features the selective introduction positive charges to the phosphorodiamidate backbone. Webelieve that PMOplus® has potentially broad therapeutic applications, especially for anti-viral therapeutics.PMO-X®. The third of these chemistries, PMO-X®, incorporates novel and proprietary chemical modifications to the PMO internucleoside linkages.We believe PMO-X® may provide enhanced in vivo potency and efficacy, as well as greater flexibility in the modulation of selective tissue targeting andcellular delivery.We believe that our PMO and PMO-based technology platforms can be used to develop novel pharmaceutical products to treat a broad range ofdiseases and address key unmet medical needs. We intend to leverage our PMO and PMO-based technology platforms, organizational capabilities, andresources to become a leading developer and marketer of a diversified portfolio of PMO and PMO-based therapeutics, especially for the treatment of rare andinfectious diseases.Material AgreementsWe believe that our RNA-targeted technology could be broadly applicable for the potential development of pharmaceutical products in manytherapeutic areas. To further exploit our core technologies, we have and may continue to enter into research, development or commercialization allianceswith universities, hospitals, independent research centers, non-profit organizations, pharmaceutical and biotechnology companies and other entities forspecific molecular targets or selected disease indications. We may-9-also selectively pursue opportunities to access certain intellectual property rights that complement our internal portfolio through license agreements or otherarrangements.University of Western AustraliaIn November 2008, we entered into an exclusive license agreement with the University of Western Australia (“UWA”), for certain patents andtechnical information relating to the use of certain antisense sequences for the treatment of DMD and in April 2013, we entered into an agreement with UWAunder which this license agreement was amended and restated (“the Amended and Restated UWA License Agreement”). The Amended and Restated UWALicense Agreement grants us specific rights to the treatment of DMD by inducing the skipping of certain exons. Our lead clinical candidate, eteplirsen, fallsunder the scope of the license granted under the Amended and Restated UWA License Agreement. Any future drug candidates developed for the treatment ofDMD by exon skipping may or may not fall under the scope of the Amended and Restated UWA License Agreement.Under the Amended and Restated UWA License Agreement, we are required to meet certain performance diligence obligations related to developmentand commercialization of products developed under the license. We believe we are currently in compliance with these obligations. In 2013, we made aninitial up-front payment to UWA of $1.1 million upon execution of the Amended and Restated UWA License Agreement. We may be required to makeadditional payments to UWA of up to $6.0 million in aggregate based on successful achievement of certain development and regulatory milestones relatingto eteplirsen and up to five additional product candidates and may also be required to pay a low-single-digit percentage royalty on net sales of productscovered by issued patents licensed from UWA during the term of the Amended and Restated UWA License Agreement. As of December 31, 2015, we were notunder any current obligation to make royalty payments to UWA until achievement of the first commercial sale.Additionally, the agreement offers us the option of purchasing royalties upfront. Under this option, we may be required to make to UWA an up-frontpayment of $30.0 million as well as $20.0 million in aggregate contingency payments upon the successful achievement of certain commercial milestones.The terms of the Amended and Restated UWA License Agreement will expire on a country-by-country basis on the expiration date of the last to expirevalid claim or patent within the patents licensed to us under this agreement or upon the earliest to occur of the following: ·failure by us or UWA to cure a breach or default of any material obligation we each have under the agreement after notice from the non-breaching party within the specified time periods; ·a mutual agreement to terminate the agreement; ·by UWA in the event a party passes a resolution to wind-up or if a receiver, administrator, trustee or person performing similar functions isappointed by a court or liquidator over any of our assets; or ·upon our notice to UWA that we no longer desire to commercialize products covered under the agreement.Currently, the latest date on which an issued patent covered by our agreement with UWA expires is November 2030 (not accounting for any patentterm extension, supplemental protection certificate or pediatric extensions that may be available), however, patents granting from pending patentapplications could result in a later expiration date.Strategic AlliancesCharley’s Fund AgreementIn October 2007, Charley’s Fund, Inc. (“Charley’s Fund”), a nonprofit organization that funds drug development and discovery initiatives specific toDMD, awarded us a research grant of approximately $2.5 million and, in May 2009, the grant authorization was increased to a total of $5.0 million. Pursuantto the related sponsored research agreement, the grant was provided to support the development of product candidates related to exon 50 skipping using ourproprietary exon-skipping technologies. As of December 31, 2015, Charley’s Fund had made payments of approximately $3.4 million to us. Revenueassociated with this research and development arrangement is recognized based on the proportional performance method. To date, we have recognizedapproximately $0.1 million as revenue. We have deferred $3.3 million of previous receipts which are anticipated to be recognized as revenue upon resolutionof outstanding performance obligations.Under the terms of the sponsored research agreement, as amended, if we and any of our strategic partners elect to discontinue the development andcommercialization of any product containing any molecular candidate arising or derived from the research sponsored by Charley’s Fund for reasons otherthan safety or efficacy, we must grant to Charley’s Fund an exclusive, royalty-bearing, fully-paid, worldwide license, with right of sublicense, to any suchproduct. Depending on whether and when Charley’s Fund obtains-10-a license to any such product, percentage royalty payments on net sales required to be made by Charley’s Fund to us under the terms of the sponsoredresearch agreement, as amended, would be in the mid-single-digits. Under the terms of the sponsored research agreement, as amended, if we are able tosuccessfully commercialize any molecular candidate arising or derived from the research sponsored by Charley’s Fund either through sales of products orthrough licensing or partnership arrangements with a third party that include rights for such third party to sell, distribute, promote or market such products orthe underlying intellectual property, we are obligated to repay the research funds paid to us by Charley’s Fund, up to an amount equal to the total amount offunds provided by Charley’s Fund to us. In connection with this repayment obligation, we agreed that we would pay a mid-single-digit percentage royalty onnet sales of products containing any molecular candidate arising or derived from the research sponsored by Charley’s Fund and a mid-teens amount of anyup-front cash and/or milestone payments received from a licensing or partnership arrangement with a third party with respect to such products (in each case,up to an amount equal to the total amount of funds provided by Charley’s Fund to us). This agreement will be terminated by its own terms at the completionof the research being sponsored by Charley’s Fund. Our technology upon which the agreement is based is covered by certain patents, the last of which expiresfollowing the termination of the agreement.Previously, we noted unexpected toxicology findings in the kidney as part of our series of preclinical studies for AVI-5038, our PMO-based candidatedesigned for the treatment of individuals with DMD who have an error in the gene coding for dystrophin that can be treated by skipping exon 50. We haveconducted additional preclinical studies and have not alleviated the toxicity problem. Pursuant to the terms of our agreement with Charley’s Fund, thereceipt of additional funds is tied to the satisfaction of certain clinical milestones. Because of the toxicity issues with AVI-5038, satisfaction of the additionalmilestones under the agreement is unlikely and we do not expect to receive any additional funds from Charley’s Fund.ManufacturingWe believe we have developed proprietary state-of-the-art manufacturing and scale-up techniques that allow synthesis and purification of our productcandidates to support clinical development as well as potential commercialization. We have entered into certain manufacturing and supply arrangementswith third-party suppliers which will in part utilize these techniques to support production of certain of our product candidates and their components. Wecurrently do not have any of our own internal mid-to-large scale manufacturing capabilities to support our product candidates.For our current development programs we have entered into supply agreements with certain large pharmaceutical manufacturing firms for theproduction of the custom raw materials required for PMO production and the APIs, for our product candidates.For our DMD program, we are working with our existing manufacturers to increase our active pharmaceutical ingredient (“API”) production capacityfrom mid-scale to large-scale. During 2016, we will also evaluate whether to increase our API production capacity to a commercial scale. This decision willdepend in significant part on our discussions with the FDA in 2016 as well as our expectations regarding clinical trial needs and the potential feasibility andtiming of the commercialization of eteplirsen.There are a limited number of companies that can produce raw materials and APIs in the quantities and with the quality and purity that we require forour DMD development efforts. Due to their technical expertise, experience in manufacturing our product candidates and sophistication of theirmanufacturing facilities and quality systems, we are considering our existing manufacturers, as well as other manufacturers with relevant expertise, for thefurther scale-up of the production of raw materials and APIs for our DMD program. Establishing a relationship with alternative suppliers can be a lengthyprocess and might cause delays in our development efforts. If we are required to seek alternative supply arrangements, the resulting delays and potentialinability to find a suitable replacement could materially and adversely impact our business.Manufacturers and suppliers of product candidates are subject to the FDA’s current Good Manufacturing Practices (“cGMP”), requirements, and otherrules and regulations prescribed by foreign regulatory authorities. We depend on our third-party suppliers and manufacturers for continued compliance withcGMP requirements and applicable foreign standards.Sales and Marketing StrategyWe have not obtained regulatory approval for any of our product candidates. Due to the rare nature of DMD and the lack of disease-modifyingtreatments, patients suffering from DMD, together with their physicians, often have a high degree of organization and are well informed, which may simplifythe identification of a target population for eteplirsen, our lead product candidate, if it is approved. We believe that, if approved for commercial sale, it willbe possible to commercialize eteplirsen with a relatively small specialty sales force that calls on the physicians, foundations and other patient-advocacygroups focused on DMD. Our current expectation is to commercialize eteplirsen ourselves in the U.S. and we continue to take steps to establish the necessarycommercial infrastructure we believe is needed for a potential marketing approval of eteplirsen. We will continue to evaluate whether to market our DMDproduct candidates outside of the U.S. ourselves or enter into arrangements with other pharmaceutical or biotechnology companies for the marketing and saleof our products outside the U.S. either globally or on a country-by-country basis.-11-Patents and Proprietary RightsOur success depends in part upon our ability to protect our core technologies and intellectual property. To accomplish this, we rely on a combinationof intellectual property rights, including patents, trade secrets, copyrights and trademarks, as well as regulatory exclusivity and contractual protections.Our patents and patent applications are directed to our product candidates as well as to our PMO and PMO-based technology platforms. We seekpatent protection for certain of our product candidates and proprietary technologies by filing patent applications in the U.S. and other countries. As ofFebruary 9, 2016, we owned or controlled approximately 380 U.S. and corresponding foreign patents and 349 U.S. and corresponding foreign patentapplications. We intend to protect our proprietary technology with additional filings as appropriate.Our product candidates and our technology are primarily protected by composition of matter and use patents and patent applications. Currently, ourclinical product candidates include eteplirsen for DMD. We have exclusively licensed patents from the UWA that provide primary patent protection foreteplirsen as follows:Patent NumberCountry/RegionPatent TypeExpiration Date*U.S. 7,807,816**United StatesComposition of MatterFebruary 23, 2026U.S. 7,960,541**United StatesComposition of MatterJune 28, 2025U.S. 8,486,907***United StatesMethods of UseJune 28, 2025U.S. 9,018,368United StatesComposition of MatterJune 28, 2025EP 1 766 010 B1EuropeComposition of Matter & Methods of UseJune 28, 2025* Stated expiration dates do not account for any patent term extension, supplemental protection certificate or pediatric extensions that may be available.** Involved in U.S. Patent Interference No. 106,008.***Involved in U.S. Patent Interference No. 106,013. Judgment dated September 29, 2015 ordered cancellation of U.S. 8,486,907. Decision dated December29, 2015 denied our Request for Rehearing and is open to appeal.In addition to the foregoing patents that protect eteplirsen, we either solely own or exclusively license from UWA patents and patent applications inthe U.S. and in major foreign markets that provide additional protection for eteplirsen as well as our DMD follow-on exon-skipping candidates (e.g., SRP-4045 and SRP-4053), which cover the composition of matter, preparation and/or uses of these drug candidates. These patents, and patent applications, ifgranted, expire between 2025 and 2034, such expiration dates not accounting for any patent term extension, supplemental protection certificate or pediatricextensions that may be available.We separately own patents and patent applications in the U.S. and in major foreign markets that cover our proprietary PMO and PMO-basedtechnologies (e.g., PPMO, PMOplus®, PMO-X®). These patents, and patent applications, if granted, expire between 2024 and 2032, such expiration datesnot accounting for any patent term extension, supplemental protection certificate or pediatric extensions that may be available. We are the owner of multiplefederal trademark registrations in the United States including, but not limited to, Sarepta®, Sarepta Therapeutics®, PMOplus®, PMO-X® and the SareptaTherapeutics logo. In addition, we have multiple pending trademark applications in the United States.Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection for our product candidates, andsuccessfully defending these patents against third-party challenges. Our ability to protect our product candidates from unauthorized making, using, selling,offering to sell or importing by third parties is dependent on the extent to which we have rights under valid and enforceable patents that cover theseactivities.We do not have patents or patent applications in every jurisdiction where there is a potential commercial market for our product candidates. For eachof our programs, our decision to seek patent protection in specific foreign markets, in addition to the U.S. is based on many factors, including: ·our available resources; ·the number and types of patents already filed or pending; ·the likelihood of success of the product candidate; ·the size of the commercial market; ·the presence of a potential competitor in the market; and ·whether the legal authorities in the market effectively enforce patent rights.-12-We continually evaluate our patent portfolio and patent strategy and believe our owned and licensed patents and patent applications provide us witha competitive advantage; however, if markets where we do not have patents or patent applications become commercially important, our business may beadversely affected.The patent positions of pharmaceutical, biotechnology and other life sciences companies can be highly uncertain and involve complex legal andfactual questions for which important legal principles remain unresolved. No consistent policy regarding the breadth of claims allowed in biotechnologypatents has emerged to date in the U.S. and tests used for determining the patentability of patent claims in all technologies are in flux. In addition, there is noassurance as to the degree and range of protections any of our patents, if issued, may afford us or whether patents will be issued. Patents which may be issuedto us may be subjected to further governmental review that may ultimately result in the reduction of their scope of protection, and pending patentapplications may have their requested breadth of protection significantly limited before being issued, if issued at all. For example, we are aware of certainclaims that our competitor BioMarin has rights to in the United States that, if granted, may provide the basis for BioMarin or other parties that have rights tothese claims to assert that our drug candidates, eteplirsen and/or SRP-4053, infringe on such claims. In 2014, the Patent Trial and Appeal Board (“PTAB”) ofthe USPTO declared various patent interferences between certain patents held by Sarepta under a license from the UWA and patent applications held byBioMarin under license from Academisch Ziekenhuis Leiden (“AZL”) related to exon 51 and exon 53 skipping therapies designed to treat DMD. Patents heldor licensed to Sarepta and included in these interference proceedings are presumed valid by statute for the duration of these proceedings and any appeals.These interferences have not changed our plans to submit an NDA for eteplirsen, continue with our clinical development plans for eteplirsen and SRP-4053or our ability to launch eteplirsen commercially if it is approved by the FDA under an accelerated approval pathway, however, if final resolution of theseinterferences and related appeals, if any, are not in our favor, our current business, development and commercialization plans for eteplirsen and SRP-4053may be negatively impacted. For details on and risks related to the interferences that PTAB has declared involving our patents, please read Risk Factors—Risks Relating to Our Business—Our success, competitive position and future revenue, if any, depend in part on our ability and the abilities of ourlicensors to obtain and maintain patent protection for our product candidates, to preserve our trade secrets, to prevent third parties from infringing on ourproprietary rights and to operate without infringing on the proprietary rights of third parties.The pharmaceutical, biotechnology and other life sciences patent situation outside the U.S. can be even more uncertain. For example, BioMarin hasrights to European Patent No. EP 1619249. We opposed this patent in the Opposition Division of the European Patent Office (“Opposition Division”), and inNovember 2011, we announced that, although we succeeded in invalidating some of the patent’s claims, the Opposition Division maintained in amendedform certain claims of this patent relating to the treatment of DMD by skipping dystrophin exons 51 and 46. We and BioMarin both appealed this decision inJune 2013; however, pending final resolution of this matter, the patent at issue may provide the basis for BioMarin or other parties that have rights to suchpatent in the relevant European country to assert that our drug candidate, eteplirsen, infringes on such patent upon launching eteplirsen in such relevantEuropean country. The outcome of the appeal cannot be predicted or determined as of the date of this report. If as part of any appeal before the EuropeanPatent Office we are unsuccessful in invalidating BioMarin’s claims that were maintained by the Opposition Division or if claims previously invalidated bythe Opposition Division are restored on appeal, our ability to commercialize both eteplirsen and other therapeutic candidates, such as SRP-4045 and SRP-4053 could be materially impaired. Moreover, our ability to commercialize eteplirsen in a European country where BioMarin has a patent related to EP1619249 while the appeal process remains ongoing before the European Patent Office Board of Appeals could be materially impaired. In addition, we areaware of various divisional applications relating to EP 1619249 that are being pursued by BioMarin, which are pending and in some cases are proceeding togrant. Should any patents grant from these applications, our ability to commercialize eteplirsen or our other therapeutic candidates, such as SRP-4045 andSRP-4053, could be materially impaired.In addition to government, court and regulatory patent decisions, changes in either the patent laws or in interpretations of patent laws in the U.S. andother countries may diminish the value of our intellectual property. Accordingly, we cannot predict the breadth of claims that may be allowed or enforced inthe patents that we own or have licensed or in third-party patents. Further, since publication of discoveries in scientific or patent literature often lags behindactual discoveries, there is no assurance that we were the first creator of inventions covered by our pending patent applications, or that we were the first to filepatent applications for these inventions.Government RegulationThe testing, manufacturing, labeling, advertising, promotion, distribution, exportation and marketing of our products are subject to extensiveregulation by governmental authorities in the U.S. and in other countries. In the U.S., the FDA, under the Federal Food, Drug and Cosmetic Act and itsimplementing regulations, regulates pharmaceutical products. Failure to comply with applicable U.S. requirements may subject us to administrative orjudicial sanctions, such as FDA refusal to approve pending NDAs, withdrawal of approval of approved products, warning letters, untitled letters, productrecalls, product seizures, total or partial suspension of production or distribution, injunctions, civil penalties and/or criminal prosecution.-13-Drug Approval ProcessTo obtain FDA approval of a product candidate, we must, first and foremost, submit clinical data providing substantial evidence of safety and efficacyof the product for its intended use, as well as detailed information on product composition, its manufacture and controls and proposed labeling. The testingand collection of data and the preparation of necessary applications are expensive and time-consuming. The FDA may not act quickly or favorably inreviewing these applications, and we may encounter significant difficulties or costs in our efforts to obtain FDA approvals that could delay or preclude usfrom marketing our products.The steps required before a drug may be approved for marketing in the U.S. generally include the following: ·preclinical laboratory tests and animal toxicity testing; ·submission of an IND application for conducting human clinical testing to the FDA, which must become effective before human clinical trialscommence; ·adequate and well-controlled human clinical trials to establish the safety and efficacy of the drug product for each indication, includingplacebo-controlled studies or comparison of treated group from clinical trials to data from natural history data or studies; ·satisfactory completion of an FDA inspection of the commercial manufacturing facilities at which the drug substance and drug product aremade to assess compliance with cGMP; ·satisfactory FDA audit of the clinical trial site(s) that generated the pivotal safety and efficacy data included in the NDA and also potentiallythe nonclinical manufacturing site(s) in the form of pre-approval inspections; and ·FDA review and approval of the NDA.Preclinical studies may include laboratory evaluations of the product chemistry, pharmacology, toxicity and formulation, as well as animal studies toassess the pharmacokinetics, metabolism, bio-distribution, elimination and toxicity of the product candidate. The conduct of the preclinical tests andformulation of the compounds for testing must comply with federal regulations and requirements. The results of the preclinical studies, manufacturinginformation, analytical data and a proposed first in human clinical trial protocol are submitted to the FDA as part of the IND, which must become effectivebefore clinical trials may be initiated. The IND will become effective approximately 30 days after receipt by the FDA, unless the FDA raises concerns orquestions about the supportive data, or the design, particularly regarding potential safety issues of conducting the clinical trial as described in the protocol.In this situation, the trials are placed on clinical hold and the IND sponsor must resolve any outstanding FDA concerns before clinical trials can proceed.Clinical trials involve the administration of the product candidate to healthy volunteers or patient participants under the supervision of a qualifiedprincipal investigator. Clinical trials are conducted under protocols detailing the objectives of the study, the administration of the investigational product,study procedures, parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as asubmission to the IND. Clinical trials must be conducted in accordance with the FDA’s Good Clinical Practice (“GCP”) requirements and federal and statelaws and regulations protecting study subjects. Further, each clinical trial must be reviewed and approved by the Institutional Review Board (“IRB”) at orservicing each institution in which the clinical trial will be conducted. The IRB will consider, among other things, rationale for conducting the trial, clinicaltrial design, participant informed consent, ethical factors, the safety and rights of human subjects and the possible liability of the institution. The FDA cantemporarily or permanently halt a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial is not being conducted in accordancewith FDA requirements or presents an unacceptable risk to the clinical trial subjects. The IRB may also require the clinical trial at a particular site be halted,either temporarily or permanently, for failure to comply with GCP or the IRB’s requirements, or may impose other conditions.Clinical trials typically are conducted in three sequential drug development phases (Phases I, II and III) prior to approval, a portion of these phasesmay overlap. A fourth post-approval phase (Phase IV) may include additional clinical studies. A general description of clinical trials conducted in each phaseof development is provided below. However, the number of study subjects involved in each phase of drug development for rare diseases can be significantlyless than typically expected for more common diseases with larger patient populations: ·Phase I. Phase I clinical trials involve the initial introduction of the drug into human subjects. These studies are usually designed to determinethe safety of single and multiple doses of the compound and determine any dose limiting toxicities or intolerance, as well as the metabolismand pharmacokinetics of the drug in humans. Phase I studies usually involve less than 100 subjects and are conducted in healthy adultvolunteers unless the drug is toxic (e.g., cytotoxics) in which case they are tested in patients. ·Phase II. Phase II clinical trials are usually conducted in a limited patient population to evaluate the safety and efficacy of the drug for aspecific indication to determine optimal dosage and to identify possible adverse effects and safety risks.-14- Phase II studies usually involve patients with the disease under investigation and may vary in size from several dozen to several hundred. ·Phase III. If an investigational drug is found to be potentially effective and to have an acceptable safety profile in early phase studies, largerPhase III clinical trials are conducted to confirm clinical efficacy, dosage and safety in the intended patient population, which may involvegeographically dispersed clinical trial sites. Generally, two adequate and well-controlled Phase III clinical trials which establish the safety andefficacy of the drug for a specific indication are required for approval of an NDA. Phase III studies usually include several hundred to severalthousand patients for larger, non-orphan drug indications/diseases. However, for orphan drug indications due to their lower prevalence, clinicaltrials for rare or orphan diseases generally have fewer patients. For these orphan diseases, a company may also try to demonstrate efficacy andsafety by comparing treated patients in clinical trials to untreated populations in placebo-controlled clinical trials or to data from naturalhistory studies. ·Phase IV. Phase IV trials are clinical studies conducted after the FDA has approved a product for marketing. Typically there are two forms ofPhase IV trials: those that are conducted to fulfill mandatory conditions of product approval and those that are voluntarily conducted to gainadditional experience from the treatment of patients in the intended therapeutic indication. The mandatory studies are used to confirm clinicalbenefit in the case of drugs approved under the accelerated approval regulations or to provide additional clinical safety or efficacy data for“full” approvals. Failure to promptly conduct and complete mandatory Phase IV clinical trials could result in withdrawal of approval forproducts approved under accelerated approval regulations.A company seeking marketing approval for a new drug in the U.S. must submit to the FDA the results of the preclinical and clinical trials, togetherwith, among other things, detailed information on the manufacture and composition of the product candidate and proposed labeling, in the form of an NDA,including payment of a user fee unless the submission is for an Orphan Indication. The FDA assesses all NDAs submitted for completeness before it acceptsthem for filing and review. FDA may request additional information before accepting an NDA for filing. Once the submission is accepted for filing, the FDAbegins an in-depth review of the NDA. Under the current NDA review goals mandated under the PDUFA, the FDA has ten months in which to complete itsinitial review of a standard NDA and respond to the applicant, and six months for a priority NDA. The FDA does not always meet its PDUFA goal dates forstandard or priority NDAs. The review process and the PDUFA goal date may be extended by three months if the FDA requests or the NDA sponsor otherwiseprovides additional information or clarification regarding information already provided in the submission within the last three months before the PDUFAgoal date. If the FDA’s evaluations of the NDA and the clinical and manufacturing procedures and facilities are favorable, the FDA may issue an approvalletter. If the FDA finds deficiencies in the NDA, it may issue a complete response letter, which defines the conditions that must be met in order to secure finalapproval of the NDA. If and when those conditions have been met to the FDA’s satisfaction, the FDA will issue an approval letter, authorizing commercialmarketing of the drug. Sponsors that receive a complete response letter may submit to the FDA information that represents a complete response to the issuesidentified by the FDA. Resubmissions by the NDA sponsor in response to a complete response letter trigger new review periods of varying length (typicallytwo to six months) based on the content of the resubmission. If the FDA’s evaluation of the NDA and the commercial manufacturing procedures and facilitiesis not favorable, the FDA may refuse to approve the NDA. The FDA may also refer an application to an advisory committee, typically comprised of a panel ofexpert clinicians and researchers, for review, evaluation and a recommendation as to whether the application should be approved for the proposed indication.The FDA is not bound by, but typically follows, the recommendations of the advisory committee.A sponsor may also seek designation of its drug candidates under programs designed to accelerate the FDA’s review and potential approval of NDAs.For instance, a sponsor may seek FDA designation of a drug candidate as a “fast track product.” Fast track products are those products intended for thetreatment of a serious or life-threatening disease or condition and which demonstrate the potential to address unmet medical needs for such disease orcondition. If fast track designation is obtained, the FDA may initiate early and frequent communication and begin reviewing sections of an NDA before theapplication is complete. This “rolling review” is available if the applicant provides, and the FDA approves, a schedule for the remaining information.Eteplirsen was granted fast track status in 2007 and both AVI-7288 and AVI-7537 were granted fast track status in September 2012.The Food and Drug Administration Safety and Innovation Act (“FDASIA”) enacted and signed into law in 2012 amended the criteria for the fast trackand accelerated approval pathways and, as a result, the pathways now share many common eligibility criteria. FDASIA provides both the sponsor companiesand the FDA with greater flexibility and expedited regulatory mechanisms. The statute clarifies that a fast track product may be approved pursuant to anaccelerated approval (Subpart – H) or under the traditional approval process. In addition, FDASIA codified the accelerated approval pathway as separate andapart from the fast track pathway, meaning that for drugs to be eligible for accelerated approval, they do not need to be designated under the fast trackpathway. FDASIA reinforces the FDA’s authority to grant accelerated approval of a drug that treats a serious condition and generally provides a meaningfuladvantage over available therapies and demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or on a clinicalendpoint that can be measured earlier than irreversible morbidity or mortality (“IMM”) that is reasonably likely to predict an effect on IMM or other clinicalbenefit (i.e., an intermediate clinical endpoint). Approvals of this kind typically include requirements for appropriate post-approval Phase IV clinical trials toconfirm clinical benefit. FDASIA retains this-15-requirement and further requires those studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit.Additionally, FDASIA established a new, expedited regulatory mechanism referred to as breakthrough therapy designation. Breakthrough therapydesignation, fast track, and accelerated approval are not mutually exclusive and are meant to serve different purposes. The breakthrough therapy designationis focused on expediting the development and review process and by itself does not create an alternate ground for product approval. A sponsor may seek FDAdesignation of a drug candidate as a breakthrough therapy if the drug is intended, alone or in combination with one or more other drugs, to treat a serious orlife-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existingtherapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The FDA issuedguidance entitled “Expedited Programs for Serious Conditions––Drugs and Biologics” in May 2014.Finally, if a drug candidate demonstrates a significant benefit over existing therapy, it may be eligible for priority review, which means it will bereviewed within a six-month timeframe from the date a complete NDA is accepted for filing.While FDASIA provides certain authorities and direction to the FDA, it is unclear how the FDA will interpret and implement FDASIA provisions, inparticular, in considering what the appropriate regulatory approval pathway is for eteplirsen. We cannot be sure that any of our drug candidates will qualifyfor any of these expedited development, review and approval programs, or that, if a drug does qualify, that the product candidates will be approved, will beaccepted as part of any such program or that the review time will be shorter than a standard review.We had multiple meetings with the FDA during 2013 and 2014 to discuss the most appropriate regulatory pathway for early registration/approval ofeteplirsen based on the Phase IIb data. In addition, we also had discussions with the FDA to finalize the confirmatory study designs for a potential acceleratedapproval for eteplirsen. Based on the data requirements and accelerated approval pathways defined by FDA, the eteplirsen NDA was prepared and submittedin June 2015. The eteplirsen NDA was filed by the FDA and granted priority review status in August 2015. Currently, review of the eteplirsen NDA isongoing. The FDA postponed a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to discuss the NDA for eteplirsenpreviously scheduled for January 22, 2016 and notified us of the a new PDUFA date of May 26, 2016.Holders of an approved NDA are required to: ·report serious adverse drug reactions to the FDA; ·submit annual and periodic reports summarizing product information and safety data; ·comply with requirements concerning advertising and promotional labeling; and ·continue to have quality control and manufacturing procedures conform to cGMP after approval.The FDA periodically inspects the sponsor’s records related to safety reporting and/or manufacturing; this latter effort includes assessment ofcompliance with cGMP. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control tomaintain cGMP compliance. Discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of anapproved NDA, including withdrawal of the product from the market.Many other countries and jurisdictions have similar drug development and regulatory review processes. We have conducted clinical trials in theUnited Kingdom and intend to submit for marketing approval in countries other than the U.S. Therefore, we will have to comply with the legal and regulatoryrequirements in the countries where we conduct trials and submit for marketing approval. We will continue to evaluate, with input from the FDA and otherregulatory authorities, which expedited programs are appropriate to incorporate in our regulatory approach for eteplirsen and our other DMD productcandidates.Orphan Drug Designation and ExclusivityIn the U.S., the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition that affects fewer than 200,000individuals in the U.S., or more than 200,000 individuals in the U.S. for which there is no reasonable expectation that the cost of developing and makingavailable in the U.S. a drug for this type of disease or condition will be recovered from sales in the U.S. for that drug. In the U.S., orphan drug designationmust be requested before submitting an application for marketing approval. An orphan drug designation does not shorten the duration of the regulatoryreview and approval process. The approval of an orphan designation request does not alter the regulatory requirements and process for obtaining marketingapproval. Safety and efficacy of a compound must be established through adequate and well-controlled studies. If a product which has an orphan drugdesignation subsequently receives FDA approval for the indication for which it has such designation, the product is generally entitled to an orphan drugexclusivity period, which means the FDA may not grant approval to any other application to market the same chemical entity for-16-the same indication for a period of seven years, except in limited circumstances, such as where an alternative product demonstrates clinical superiority to theproduct with orphan exclusivity. In addition, holders of exclusivity for orphan drugs are expected to assure the availability of sufficient quantities of theirorphan drugs to meet the needs of patients. Failure to do so could result in the withdrawal of orphan exclusivity for the drug.Distinct from orphan drug exclusivity, the FDA may provide six months of pediatric exclusivity to a sponsor of an NDA, if the sponsor conducted apediatric study or studies of such product. This process is applied to products developed for adult use and is initiated by the FDA as a written request forpediatric studies that applies to a sponsor’s product. If the sponsor conducts qualifying studies and the studies are accepted by the FDA, then an additionalsix months of pediatric exclusivity will be added to previously granted exclusivity, such as orphan drug exclusivity and new chemical entity exclusivity.Competitors may receive approval of different drugs or biologics for the indications for which a prior approved orphan drug has exclusivity. We have beengranted orphan drug designation for eteplirsen, AVI-7288, AVI-7537 and AVI-5038 in the U.S.In Europe, Orphan Medicinal Product designation is considered by the European Medicines Agency (“EMA”) for drugs intended to diagnose, preventor treat a life-threatening or very serious condition afflicting five or fewer out of 10,000 people in the E.U., including compounds for serious and chronicconditions that would likely not be marketed without incentives due to low market return on the sponsor’s development investment. The medicinal productconsidered should be of significant benefit to those affected by the condition as compared to previously approved products for the same indication. Benefitsof being granted orphan designation are significant, including up to ten years of market exclusivity. During this ten-year period, the EMA may not accept anew marketing application for a similar drug for the same therapeutic indication as the orphan drug. Distinct from orphan drug exclusivity, the EMA mayprovide a sponsor having an approved Pediatric Investigation Plan (“PIP”) or pediatric exclusivity waiver, which may lead to a two-year extension of marketexclusivity beyond the original ten-year period of orphan drug exclusivity. We have been granted orphan drug designation for eteplirsen and AVI-5038 inthe E.U.Ex-U.S. Regulatory RequirementsIn addition to regulation by the FDA and certain state regulatory agencies, we are also subject to a variety of foreign regulations governing clinicaltrials and the marketing of other medicinal products. Outside of the U.S., our ability to market a product depends upon receiving a marketing authorizationfrom the appropriate regulatory authorities. The requirements governing the conduct of clinical trials, applications for marketing authorization, pricing andreimbursement vary widely from country to country. In any country, however, we will only be permitted to commercialize our products if the appropriateregulatory authority is satisfied that we have presented adequate evidence of safety, quality and efficacy. Whether or not FDA approval has been obtained,approval of a product by the comparable regulatory authorities of foreign countries must be obtained prior to the commencement of marketing of the productin those countries. The time needed to secure approval may be longer or shorter than that required for FDA approval. The regulatory approval and oversightprocess in other countries includes all of the risks associated with regulation by the FDA and certain state regulatory agencies as described above.Other Regulatory RequirementsIn addition to regulations enforced by the FDA and foreign authorities relating to the clinical development and marketing of products, we are or maybecome subject to regulation under the Occupational Safety and Health Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Actand other present and potential future foreign, federal, state and local laws and regulations. Although we believe that we are in material compliance withapplicable environmental laws that apply to us, we cannot predict whether new regulatory restrictions will be imposed by state or federal regulators andagencies or whether existing laws and regulations will adversely affect us in the future.Pharmaceutical Pricing and ReimbursementIn both U.S. and foreign markets, our ability to commercialize our products successfully and to attract commercialization partners for our products,depends in significant part on the availability of adequate financial coverage and reimbursement from third-party payers, including, in the U.S.,governmental payers such as the Medicare and Medicaid programs, managed care organizations and private health insurers. Third-party payers areincreasingly challenging the prices charged for medicines and examining their cost effectiveness, in addition to their safety and efficacy. We may need toconduct expensive pharmacoeconomic studies in order to demonstrate the cost effectiveness of our products. Even with the availability of such studies, ourproducts may be considered less safe, less effective or less cost-effective than alternative products, and third-party payers may not provide coverage andreimbursement for our product candidates, in whole or in part.Political, economic and regulatory influences are subjecting the healthcare industry in the U.S. to fundamental changes. There have been, and weexpect there will continue to be, legislative and regulatory proposals to change the healthcare system in ways that could significantly affect our business,including the Patient Protection and Affordable Care Act of 2010. We anticipate that the U.S.-17-Congress, state legislatures and the private sector will continue to consider and may adopt healthcare policies intended to curb rising healthcare costs. Thesecost containment measures include: ·controls on government funded reimbursement for drugs; ·mandatory discounts under certain government sponsored programs; ·controls on healthcare providers; ·challenges to the pricing of drugs or limits or prohibitions on reimbursement for specific products through other means; ·reform of drug importation laws; and ·expansion of use of managed care systems in which healthcare providers contract to provide comprehensive healthcare for a fixed cost perperson.We are unable to predict what additional legislation, regulations or policies, if any, relating to the healthcare industry or third party coverage andreimbursement may be enacted in the future or what effect such legislation, regulations or policies would have on our business. Any cost containmentmeasures, including those listed above, or other healthcare system reforms that are adopted could have a material adverse effect on our business prospects.CompetitionThe pharmaceutical and biotechnology industries are intensely competitive, and any product candidate developed by us would likely compete withexisting drugs and therapies. There are many pharmaceutical companies, biotechnology companies, public and private universities, government agencies andresearch organizations that compete with us in developing various approaches to the treatment of rare and infectious diseases. Many of these organizationshave substantially greater financial, technical, manufacturing and marketing resources than we have. Several of them have developed or are developingtherapies that could be used for treatment of the same diseases that we are targeting. In addition, many of these competitors have significantly greatercommercial infrastructures than we have. Our ability to compete successfully will depend largely on: ·our ability to complete clinical development and obtain regulatory approvals for our product candidates; ·the efficacy, safety and reliability of our product candidates; ·the timing and scope of regulatory approvals; ·product acceptance by physicians and other health-care providers; ·protection of our proprietary rights and the level of generic competition; ·the speed at which we develop product candidates; ·our ability to supply commercial quantities of a product to the market; ·obtaining reimbursement for product use in approved indications; ·our ability to recruit and retain skilled employees; and ·the availability of substantial capital resources to fund development and commercialization activities, including the availability of fundingfrom the U.S. government.DMD Program Competition. Currently, no disease-modifying product has been granted full approval for the treatment of DMD and no product iscommercially available outside the European Economic Area (“EEA”). Companies including, but not limited to, BioMarin Pharmaceuticals, Inc.(“BioMarin”) and PTC Therapeutics, Inc., (“PTC”), have product candidates in development for the treatment of DMD. Nippon Shinyaku has reported earlyclinical development data for an exon 53 skipping candidate, and it is unknown if further clinical development of this or other exon-skipping compounds isplanned. PTC has a small molecule candidate, ataluren, which targets nonsense mutations in development. The European Commission granted conditionalmarketing authorization for ataluren for the treatment of a subset of DMD patients in August 2014. In January 2016, PTC announced the completion of itsrolling submission of an NDA for ataluren to the FDA and submission of its Phase III Ataluren Confirmatory Trial (“ACT”) DMD clinical trial result to theEMA. Ataluren uses a distinct scientific approach that addresses a different genotype of DMD patients compared to eteplirsen. Therefore, we do not believeataluren is appropriate for the treatment of DMD patients that are amenable to exon-skipping therapy. Additionally companies such as Santhera, Summit,Pfizer and Tivorsan have unique product candidates in different stages of development or approval in DMD which we believe could be seen ascomplementary to exon skipping and not a direct replacement of our clinical candidates at this time.-18-BioMarin has an exon 51-skipping product candidate, drisapersen. An NDA for drisapersen was filed by the FDA and a marketing authorizationapplication was submitted to the EMA in June 2015. In January 2016, the FDA issued a complete response letter and declined the approval for drisapersen forthe treatment of DMD. Drisapersen was previously owned by Prosensa. The Prosensa program commenced treatment in December 2010 in a Phase III clinicalstudy in ambulant individuals with DMD who have a dystrophin gene mutation amenable to treatment by skipping exon 51. This randomized, placebo-controlled study was fully enrolled, with approximately 180 participants who were being dosed for 48 weeks. The primary efficacy endpoint for Prosensa’sstudy was a measure of muscle function using the 6MWT. In September 2013, GSK and Prosensa announced that the Phase III clinical study of drisapersendid not meet the primary endpoint of a statistical significant improvement in the 6MWT compared to placebo. In September 2010, the Prosensa / GSKprogram commenced a Phase II double-blind, placebo-controlled study. This study is designed to assess the efficacy of two different dosing regimens ofGSK2402968 administered over 24 weeks in DMD patients, and then to continue observing the patients over a second 24-week interval for a total study timeframe of 48 weeks. This study completed enrollment with 54 DMD patients in October 2011 and has since concluded. Another study using GSK2402968 innon-ambulatory DMD patients has been initiated using a 6 mg/kg dose and is anticipated to enroll 20 patients. Like BioMarin, other companies continue topursue approval of products for the treatment of DMD and their products may or may not prove to be safer and/or more efficacious than, or obtain marketingapproval before, eteplirsen.Additionally, several companies have recently entered into collaborations or other agreements for the development of product candidates, includingmRNA, gene (CRISPR, AAV, etc.) or small molecule therapies that are potential competitors for therapies being developed in the muscular dystrophy,neuromuscular and rare disease space, including but not limited to Biogen Inc., Ionis, Alexion Pharmaceuticals, Inc., Sanofi, Eli Lilly, AlnylamPharmaceuticals, Inc., Moderna Therapeutics, Inc., Summit plc, Akashi, Catabasis and Oxford University.Hemorrhagic Fever Virus Program Competition. No specific treatment has been proven effective, and no approved vaccine currently exists fortreatment or prophylaxis of either Ebola virus or Marburg virus. These agents must be tested extensively in animals and meet strict government regulations.Investigational compounds can only be tested for efficacy in humans during outbreak situations such as the recent Ebola outbreak in West Africa that beganin early 2014. The exigency and scale of the 2014 Ebola virus outbreak in West Africa has accelerated the development of both treatments and vaccines forEbola. Several vaccine candidates have reached the clinical development stage and are actively being tested for population safety and potentially efficaciousimmunoprotective effect as a prophylactic agent. These include vaccine candidates sponsored by the biotechnology industry and also candidates indevelopment by U.S. government agencies (e.g., the NIAID and the DoD). The U.S. government is also supporting early stage research on therapeutics againsthemorrhagic fever viruses, including broad-spectrum therapeutics. Among the most advanced therapeutic candidates that might have utility in combatingEbola virus, are candidates being developed by the Tekmira Pharmaceutical Corp., Toyama Chemical Co. LTD, BioCryst Pharmaceuticals Inc., and MappBiopharmaceutical Inc. with the support of the U.S. government. Additionally, investigation of the use of convalescent plasma containing Ebola virusantibodies as a treatment modality, as well as for the potentially efficacious repurposing of drugs not intended to treat Ebola virus, remain an ongoing pursuitby the biopharmaceutical industry and several national government agencies.Influenza Program Competition. Currently, there are three therapeutic products for influenza that have received market approval from the FDA and arerecommended for use in the U.S. These are: (1) oseltamivir (Tamiflu), a Roche Holding and Gilead product; (2) zanamivir (Relenza), a GSK product; and(3) peramivir (Rapivab), a BioCryst Pharmaceuticals Inc. product. In addition to these products, Biota Pharmaceuticals and Daiichi Sankyo’s laninamivir waslaunched in 2010 in Japan. Currently, funding from the United States Department of Health and Human Services (“DHHS”) Biomedical Advanced Researchand Development Authority is helping support clinical trials of, Romark Laboratories’ nitazoxanide. In addition, other companies have influenza therapeuticcompounds against viral and host targets in various stages of development, including Vertex Pharmaceutical and Janssen Pharmaceutical’s VX-787, BiotaPharmaceutical’s laninamivir, Autoimmune Technologies flufirvitide-3, Ansun BioPharma’s fludase, and Toyama Chemical’s favipiravir which is in a PhaseII clinical trial in the United States, under a DoD contract with MediVector, Inc., and has completed a Phase III trial in Japan. Several additional companies,including Crucell Inc., Celltrion Inc., Visterra Inc. and Genentech Inc. are also currently developing monoclonal antibodies for use against various influenzastrains to confer passive or active immunotherapeutic response. DHHS is currently seeking additional antiviral therapeutics for the treatment of influenzainfections.In addition to therapeutic products, other companies are focusing development efforts on universal influenza vaccines, including BiondVaxPharmaceuticals Ltd. and Immune Targeting Systems which are in Phase II and Dynavax in Phase I clinical trials. Successful development of a universalinfluenza vaccine could lead to a reduction in the number of influenza cases and, therefore, the market size.Platform Technology Competition. We believe that other biotechnology and pharmaceutical companies share a focus on RNA-targeted drug discoveryand development. Competitors with respect to our RNA-targeted technologies include, but are not limited to, Alnylam, Tekmira Pharmaceuticals Corp., Ionis,BioMarin, Sanofi, Synthena AG and Santaris Pharma A/S. -19-EmployeesAs of December 31, 2015, we had 270 employees, 114 of whom hold advanced degrees. Of these employees, 161 are engaged directly in research anddevelopment activities and 109 are in general and administration including 33 in the sales force. None of our employees are covered by collective bargainingagreements and we consider relations with our employees to be good. Item 1A. Risk Factors.Factors That Could Affect Future ResultsSet forth below and elsewhere in this report and in other documents we file with the SEC are descriptions of risks and uncertainties that could causeactual results to differ materially from the results contemplated by the forward-looking statements contained in this report. Because of the following factors,as well as other variables affecting our operating results, past financial performance should not be considered a reliable indicator of future performanceand investors should not use historical trends to anticipate results or trends in future periods. The risks and uncertainties described below are not the onlyones facing us. Other events that we do not currently anticipate or that we currently deem immaterial also affect our results of operations and financialcondition.Risks Related to Our BusinessMost of our product candidates are at an early stage of development and may never receive regulatory approval.Our most advanced product candidate is eteplirsen for which the FDA is reviewing a new drug application (“NDA”) with a Prescription Drug User FeeAct (“PDUFA”) action date of May 26, 2016. Eteplirsen is still being evaluated in several clinical studies, including a confirmatory clinical trial. The exon53-skipping product candidate, which we are working on with the SKIP-NMD consortium, is currently in the clinic and we have completed Part I and havestarted Part II of a Phase I/IIa clinical trial in the E.U. We are also in the process of conducting a placebo-controlled dose titration study for our exon 45-skipping product candidate. Additionally, we are working towards initiating a clinical trial in the U.S. and the E.U. for exon 45- and 53-skipping productcandidates and have satisfactorily responded to the FDA’s inquiries on pre-clinical data for this study relating to our exon-53 product candidate. Theremainder of our product candidates are in early stages of development. These product candidates will require significant further development, financialresources and personnel to develop into commercially viable products and obtain regulatory approval, if at all. Currently, eteplirsen, our exon 45-skippingproduct candidate, the exon 53-skipping product candidate we are developing with the SKIP-NMD consortium, each for DMD, and AVI-7100 in influenza arein active clinical development. AVI-7537 in Ebola and AVI-7288 in Marburg were being developed through a program with the U.S. Department of Defense(the “DoD”) and further development is conditioned in part on obtaining additional funding, collaborations or emergency use. Our other product candidates,including our anti-bacterials, are in preclinical development or inactive. We expect that much of our effort and many of our expenditures over the nextseveral years will be devoted to clinical development and regulatory activities associated with eteplirsen and other exon-skipping candidates as part of ourlarger pan-exon strategy in DMD, our infectious disease candidates, our proprietary chemistry, and other potential therapeutic areas that provide long-termmarket opportunities. We may be delayed, restricted, or unable to further develop our active and other product candidates or successfully obtain approvalsneeded to market them.Our RNA-targeted antisense technology has not been incorporated into a therapeutic commercial product and is still at an early stage of development.Our RNA-targeted platforms, utilizing proprietary PMO-based technology, have not been incorporated into a therapeutic commercial product and arestill at an early stage of development. This technology is used in all of our product candidates, including eteplirsen. Although we have conducted and are inthe process of conducting clinical studies with eteplirsen, an exon 45-skipping product candidate and an exon 53-skipping product candidate and preclinicalstudies with our other product candidates that use our PMO-based antisense technology, additional studies may be needed to determine the safety andefficacy of our PMO-based antisense technology. In addition, nonclinical models used to evaluate the activity and toxicity of product candidate compoundsare not necessarily predictive of toxicity or efficacy of these compounds in the treatment of human disease. As such, there may be substantially differentresults observed in clinical trials from those observed in preclinical studies. Any failures or setbacks in developing or utilizing our PMO-based technology,including adverse effects in humans, could have a detrimental impact on our product candidate pipeline and our ability to maintain and/or enter into newcorporate collaborations regarding these technologies, which would negatively affect our business and financial condition.-20-We have been granted orphan drug designations in the U.S. and in the E.U. for certain of our product candidates, however, there can be no guarantee thatwe will maintain orphan status for these product candidates nor that we will receive orphan drug approval and hence prevent third parties fromdeveloping and commercializing products that are competitive to these product candidates in the absence of other barriers to entry.To date we have been granted orphan drug designation under the Orphan Drug Act by the FDA for two of our product candidates in DMD (includingeteplirsen), AVI-7537 for the treatment of Ebola virus and AVI-7288 for the treatment of the Marburg virus. Upon approval from the FDA of an NDA, productsgranted orphan drug status are generally provided with seven years of marketing exclusivity in the U.S., meaning the FDA generally will not approveapplications for other product candidates for the same orphan indication that contain the same active ingredient. Even if we are the first to obtain approval ofan orphan product and are granted exclusivity in the United States, there are limited circumstances under which a later competitor product may be approvedfor the same indication during the seven-year period of marketing exclusivity, such as if the later product is shown to be clinically superior to our product ordue to an inability to assure a sufficient quantity of the orphan drug.We also have been granted orphan medicinal product designations in the E.U. for two of our product candidates in DMD (including eteplirsen).Product candidates granted orphan status in Europe can be provided with up to 10 years of marketing exclusivity, meaning that another application formarketing authorization of a later similar medicinal product for the same therapeutic indication will generally not be approved in Europe during that timeperiod. Although we may have product candidates that may obtain orphan drug exclusivity in Europe, the orphan status and associated exclusivity periodmay be modified for several reasons, including a significant change to the orphan medicinal product designations or status criteria after market authorizationof the orphan product (e.g., product profitability exceeds the criteria for orphan drug designation), problems with the production or supply of the orphandrug, or a competitor drug, although similar, is safer, more effective or otherwise clinically superior than the initial orphan drug.We are not guaranteed to receive or maintain orphan status for our current or future product candidates, and if our product candidates that are grantedorphan status were to lose their status as orphan drugs or the marketing exclusivity provided for them in the United States or the E.U., our business and resultsof operations could be materially adversely affected. While orphan status for any of our products, if granted or maintained, would provide market exclusivityin the United States and the E.U. for the time periods specified above, we would not be able to exclude other companies from manufacturing and/or sellingproducts using the same active ingredient for the same indication beyond the exclusivity period applicable to our product on the basis of orphan drug status.In addition, we cannot guarantee that another company will not receive approval to market a product candidate that is granted orphan drug status in theUnited States or the E.U. for a product candidate that has the same active ingredient or is a similar medicinal product for the same indication as any of ourproduct candidates for which we plan to file an NDA or marketing authorization application (“MAA”). If that were to happen, any pending NDA or MAA forour product candidate for that indication may not be approved until the competing company’s period of exclusivity has expired in the United States or theE.U., as applicable. Further, application of the orphan drug regulations in the United States and Europe is uncertain, and we cannot predict how the respectiveregulatory bodies will interpret and apply the regulations to our or our competitors’ product candidates.Even if we receive regulatory approvals for any of our product candidates, it is possible that they may not become commercially viable products.Even if a product candidate receives regulatory approval, the product may not gain market acceptance among physicians, patients, healthcare or third-party payers or the medical community which could limit commercialization of the product. Assuming that any of our product candidates receives therequired regulatory approvals, commercial success will depend on a number of factors, including but not limited to the following: ·demonstration and/or confirmation of clinical efficacy and safety and acceptance of the same by the medical community; ·cost-effectiveness of the product; ·the availability of adequate reimbursement by third parties, including government payers such as the Medicare and Medicaid programs,managed care organizations and private health insurers; ·the product’s potential advantage over alternative or competitive treatment methods; ·whether the product can be manufactured in commercial quantities and at acceptable costs; ·marketing and distribution support for the product; ·any exclusivities or patent rights applicable to the product; ·the market-size for the product which may be different than expected; and-21- ·our ability to achieve and sustain profitability, which may not occur if we are unable to develop and commercialize any of our productcandidates, development is delayed or sales revenue from any product candidate that receives marketing approval is insufficient.If there are significant delays in obtaining or we are unable to obtain or maintain required regulatory approvals, we will not be able to commercialize ourproduct candidates in a timely manner or at all, which would materially impair our ability to generate revenue and have a successful business.The research, testing, manufacturing, labeling, approval, commercialization, marketing, selling and distribution of drug products are subject toextensive regulation by applicable local, regional and national regulatory authorities and regulations may differ from jurisdiction to jurisdiction. In theUnited States, approvals and oversight from federal (e.g., FDA), state and other regulatory authorities are required for these activities. Sale and marketing ofour product candidates in the United States or other countries is not permitted until we obtain the required approvals from the applicable regulatoryauthorities. Our ability to obtain the government or regulatory approvals required to commercialize any of our product candidates, including eteplirsen, onan accelerated approval (e.g., under the Food and Drug Administration Safety and Innovation Act of 2012 (“FDASIA”)) or any other basis, in any jurisdiction,including in the United States, cannot be assured, may be significantly delayed or may never be achieved for various reasons including the following: ·Our preclinical, clinical, Chemistry, Manufacturing and Controls (“CMC”) and other data and analyses from past, current and future studies forany of our product candidates may not be sufficient to meet regulatory requirements for submissions, advisory committee panels, filings orapprovals. The FDA could disagree with our beliefs, interpretations and conclusions regarding data we submit in connection with an NDAsubmission, including the eteplirsen NDA, or other product candidates, and may delay, reject or refuse to file or approve any NDA submissionwe make or provide a complete response letter until we meet their additional requirements, if ever. In addition, an advisory committee coulddetermine our data are insufficient to provide a positive recommendation for approval of any NDA we submit to the FDA. Even if we meet FDArequirements and an advisory committee votes to recommend approval of an NDA submission, the FDA could still deny approval of ourproduct candidates based on their review of the data or other factors. Each of these risks all apply to our eteplirsen NDA which is the only NDAwe have submitted to the FDA for review to date. ·The regulatory approval process for product candidates targeting orphan diseases, such as DMD, that use new technologies and processes, suchas antisense oligonucleotide therapies, and novel endpoints, such as natural history data and dystrophin measures, is uncertain due to, amongother factors, evolving interpretations of a new therapeutic class, the broad discretion of regulatory authorities, lack of precedent, varyinglevels of applicable expertise of regulators or their advisory committees, scientific developments, changes in the competitor landscape, shiftingpolitical priorities and changes in applicable laws, rules or regulations and interpretations of the same. We cannot be sure that any of ourproduct candidates, including eteplirsen, will qualify for accelerated approval under FDASIA or any other expedited development, review andapproval programs, or that, if a drug does qualify, that the product candidates will be approved, will be accepted as part of any such program orthat the review time will be shorter than a standard review. As a result of uncertainty in the approval process, we may not be able to anticipate,prepare for or satisfy requests or requirements from regulatory authorities, including completing and submitting planned INDs and NDAs forour product candidates, in a timely manner, or at all. Examples of such requests or requirements could include, but are not limited to,conducting additional or redesigned trials and procedures (e.g., additional patient muscle biopsies and dystrophin analyses), repeating orcompleting additional analysis of our data, or providing additional supportive data. In addition, an advisory committee or regulators maydisagree with our data analysis, interpretations and conclusions at any point in the approval process, which could negatively impact the reviewof our NDA or result in a decision by the Company not to proceed with development of a product candidate or an NDA submission for aproduct candidate based on feedback from regulators. For example, in reviewing the dystrophin data and analysis that we submitted foreteplirsen, the FDA previously expressed concerns with dystrophin as a surrogate endpoint and requested an independent assessment ofdystrophin positive fibers measured in our eteplirsen Phase IIb study, which we provided. The FDA has also requested natural history data tobetter evaluate the ongoing clinical results of our eteplirsen 201/202 study, which we have also provided. Any material inconsistenciesbetween our existing data and analysis and any new analyses and additional data we provide to the FDA, including the independent assessmentof dystrophin positive fibers, safety data, natural history and data from a fourth biopsy that we have provided, could negatively impact thereview of our eteplirsen NDA submission. While our studies demonstrate statistical significance, the FDA may not consider our six-minute walktest (“6MWT”) results, including our comparison of our 6MWT results to matched external natural history data, or, to the extent the FDAconsiders dystrophin a relevant biomarker, the dystrophin production observed in our studies, as demonstration of, or reasonably likely topredict a clinical benefit. Additionally, the FDA may determine, after evaluating the totality of our data and analysis package for a productcandidate, or receiving the vote of an advisory committee, that such package does not support an NDA approval.-22- ·We may not have the resources required to meet regulatory requirements and successfully navigate what is generally a lengthy, expensive andextensive approval process for commercialization of drug product candidates. Any failure on our part to respond to these requests in a timelyand satisfactory manner could significantly delay or negatively impact our placebo-controlled confirmatory study timelines and/or thedevelopment plans we have for the exon 53- and exon 45-skipping product candidates. Responding to requests from regulators and meetingrequirements for clinical studies, submissions, filings, advisory committees and approvals may require substantial personnel, financial or otherresources, which, as a small pre-commercial biopharmaceutical company, we may not be able to obtain in a timely manner or at all. In addition,our ability to respond to requests from regulatory authorities that involve our agents, third-party vendors and associates may be complicated byour own limitations and those of the parties we work with. For example, changes to CMC processes for the production of eteplirsen may requirecoordination with our third-party manufacturers, which may or may not be limited in their abilities to execute such regulatory requests. It maybe difficult or impossible for us to conform to regulatory guidance or successfully execute our product development plans in response toregulatory guidance, including related to clinical trial design and the timing of regulatory decisions with respect to any NDA submissions.Due to the above factors, among others, our product candidates could take a significantly longer time to gain regulatory approval than we expect, ormay never gain regulatory approval, which would delay or eliminate any potential commercialization or product revenue for us. Even if we are able tocomply with all regulatory requests and requirements, the delays resulting from satisfying such requests and requirements, the cost of compliance, or theeffect of regulatory decisions (e.g., limiting labeling and indications requested by us for a product candidate) may no longer make commercialization of aproduct candidate desirable for us from a business perspective, which could lead us to decide not to commercialize a product candidate.Even after approval and commercialization of a product candidate, we would remain subject to ongoing regulatory compliance and oversight tomaintain our approval. Conducting our confirmatory studies could take years to complete, yield negative results or the FDA could determine that they do notprovide the safety and efficacy requirements to maintain regulatory approval. If we are not able to maintain regulatory compliance, we may be subject to civiland criminal penalties or we may not be permitted to continue marketing our products, which could have a material adverse effect on our financial conditionand harm our competitive position in the market place.Our preclinical and clinical trials may fail to demonstrate acceptable levels of safety, efficacy, and quality of our product candidates, which could preventor significantly delay their regulatory approval.To obtain the requisite regulatory approvals to market and sell any of our product candidates, we must demonstrate, through extensive preclinical andclinical studies that the product candidate is safe and effective in humans. Ongoing and future preclinical and clinical trials of our product candidates maynot show sufficient safety, efficacy or adequate quality to obtain or maintain regulatory approvals. Furthermore, success in preclinical and early clinical trialsdoes not ensure that the subsequent trials we plan to conduct will be successful, nor does it predict final results of a confirmatory trial. If our study data do notconsistently or sufficiently demonstrate the safety or efficacy of any of our product candidates, then the regulatory approvals for such product candidatescould be significantly delayed as we work to meet approval requirements, or, if we are not able to meet these requirements, such approvals could be withheld.For example, in 2012, we completed Study 201, a U.S.-based Phase IIb 12-person clinical trial for eteplirsen at 30 mg/kg and 50 mg/kg. Followingcompletion of this study, we initiated Study 202, an ongoing open label extension study with the same participants from Study 201. These trials wereinitiated, in part, to further demonstrate efficacy and safety, including the production of dystrophin, and explore and identify a more consistently effectivedose that may be more appropriate for future clinical trials. While Studies 201 and 202 demonstrated dystrophin production based on the measurements takenat weeks 24 and 48, respectively, and 6MWT results reported for weeks 62, 74, 84, 96 and 120 supported stabilization of disease progression, we cannotprovide assurances that data from the ongoing open label extension study will continue to be positive or consistent through the study periods or that theinterpretation by regulators, such as the FDA, of the data we collect for our product candidates, including for eteplirsen, will be consistent with ourinterpretations. For example, on July 10, 2014, we announced that the 6MWT results for week 144 in Study 202 showed a change in decline from 5%, whichwas observed prior to 144 weeks, to approximately 8.5%. Additionally, on January 12, 2015, we announced results for week 168 in Study 202, which showedcontinued ambulation across all patients evaluable on the test, however patients showed a decline in distance walked on this measure since the week 144time point. Further, on October 1, 2015 we announced additional clinical efficacy and safety data that demonstrated that (i) eteplirsen provided a statisticallysignificant advantage of 151 meters in the ability of study participants to walk at three years versus an untreated external DMD control, (ii) eteplirsen-treatedpatients (n=12) experienced a slower rate of decline through week 192 versus untreated external DMD controls and (iii) the eteplirsen safety profile remainedconsistent with prior results. In January 2016, the FDA made public our eteplirsen Briefing Document Addendum (the “January 2016 Addendum”), whichdisclosed that at four years, 10 out of 12 patients on eteplirsen remained ambulatory while 10 out of 13 untreated patients in the external control had lostambulation (one patient in the external control was still ambulatory at year four, while two patients in the external control were missing data at four years), astatistically significant difference. In addition, the January 2016 Addendum disclosed a statistically significant advantage of 162 meters in the ability ofstudy participants to walk (as measured by the 6MWT) at four years. -23-If we do not obtain the required approvals to initiate the confirmatory trial for eteplirsen using our exon 45- and 53-skipping product candidates, thedata from the confirmatory studies for eteplirsen do not produce the safety and efficacy data required by the FDA for obtaining or maintaining marketingapproval, or the FDA does not accept the results of our eteplirsen confirmatory studies as supporting evidence of efficacy, we may need to continue workingwith the FDA on the design and subsequent execution of any further studies or analysis we plan to conduct or that may be required to obtain and maintainapproval of eteplirsen or our other DMD product candidates. Any significant delays or negative developments in the confirmatory studies for eteplirsen coulddelay or otherwise negatively impact our development plans for our follow-on DMD product candidates. For example, in October 2014, we received meetingminutes from a Type B pre-NDA meeting that took place in September 2014 in which the FDA provided updated guidance regarding the information to beprovided as part of, or at the time of, our NDA submission for eteplirsen. The guidance stated that the FDA was requiring additional data as part of the NDAsubmission, including the results from an independent assessment of dystrophin images, the 168 week clinical data from Study 202, and additional safetydata from new patients exposed to eteplirsen, specifying the minimum number of patients and minimum duration of exposure. Additionally, the guidancealso required patient-level natural history data to be obtained by us from independent academic institutions and requested MRI data from a recent studyconducted by an independent group. Although we continue to work to provide the FDA with the additional data and information requested, it may notsupport or result in a positive recommendation of an advisory committee or the approval of our eteplirsen NDA submission. We currently rely on third parties in the manufacturing process to produce our product candidates and our dependence on these parties, including anyinability on our part to accurately anticipate product demand and timely secure manufacturing capacity to meet actual clinical or commercial productdemand may impair the advancement of our research and development programs and potential commercialization of our product candidates.We currently do not have the internal ability to undertake the manufacturing process for our product candidates in the quantities needed to conductour research and development programs, supply clinical trials or meet commercial demand. Therefore, we rely on and expect to continue relying on for theforeseeable future, a limited number of third parties to manufacture and supply materials (including raw materials and subunits), drug substance (“API”) anddrug product, as well as to perform additional steps in the manufacturing process, such as the filling and labeling of vials and storage of our productcandidates. There are a limited number of third parties with facilities and capabilities suited for the manufacturing process of our product candidates whichcreates a heightened risk that we may not be able to obtain materials and APIs in the quantity and purity that we require. Any interruption of the developmentor operation of those facilities due to, among other reasons, events such as order delays for equipment or materials, equipment malfunction, quality controland quality assurance issues, regulatory delays and possible negative effects of such delays on supply chains and expected timelines for product availability,production yield issues, shortages of qualified personnel, discontinuation of a facility or business or failure or damage to a facility by natural disasters, couldresult in the cancellation of shipments, loss of product in the manufacturing process or a shortfall in available product candidates or materials.If these third parties were to cease providing quality manufacturing and related services to us, and we are not able to engage appropriate replacementsin a timely manner, our ability to have our product candidates manufactured in sufficient quality and quantity required for planned preclinical testing,clinical trials and potential commercial use would be adversely affected.Sarepta, through its third party manufacturers, has produced or is in the process of producing clinical and commercial supply, including for eteplirsen,based on its current understanding of market demands and planned clinical studies. In light of the limited number of third parties with the expertise toproduce our product candidates, the lead time needed to manufacture them, and the availability of underlying materials, we may not be able to, in a timelymanner or at all, establish or maintain sufficient commercial manufacturing arrangements on the commercially reasonable terms necessary to provideadequate supply of our product candidates to meet demands that exceed our clinical or commercial assumptions. Further, we may not be able to obtain thesignificant financial capital that may be required in connection with such arrangements. Even after successfully engaging third parties to execute themanufacturing process for our product candidates, such parties may not comply with the terms and timelines they have agreed to for various reasons, some ofwhich may be out of their or our control, which could impact our ability to execute our business plans on expected or required timelines in connection withthe regulatory approval process and potential commercialization. We may also be required to enter into long-term manufacturing agreements that containexclusivity provisions and/or substantial termination penalties which could have a material adverse effect on our business prior to and aftercommercialization of any of our product candidates.The third parties we use in the manufacturing process for our product candidates may fail to comply with cGMP regulations.Our contract manufacturers are required to produce our materials, APIs and drug products under current Good Manufacturing Practice regulations(“cGMP”). We and our contract manufacturers are subject to periodic unannounced inspections by the FDA and corresponding state and foreign authorities toensure strict compliance with cGMP and other applicable government regulations and corresponding foreign requirements. We do not have control over athird-party manufacturer’s compliance with these regulations and requirements. In addition, changes in cGMP could negatively impact the ability of ourcontract manufacturers to complete the manufacturing process of our product candidates in a compliant manner on the schedule we require for clinical trialsor for potential-24-commercial use. The failure to achieve and maintain high quality compliance, including failure to detect or control anticipated or unanticipatedmanufacturing errors, could result in patient injury or death or product recalls. Any difficulties or delays in our contractors’ manufacturing and supply ofproduct candidates, or any failure of our contractors to maintain compliance with the applicable regulations and requirements could increase our costs, makeus postpone or cancel clinical trials, prevent or delay regulatory approvals by the FDA and corresponding state and foreign authorities, prevent the importand/or export of our products, cause us to lose revenue, result in the termination of the development of a product candidate, or have our product candidatesrecalled or withdrawn from use.We may not be able to successfully scale up manufacturing of our product candidates in sufficient quality and quantity or within sufficient timelines, or beable to secure ownership of intellectual property rights developed in this process, which could delay or prevent us from developing or commercializing ourproduct candidates.As we prepare for larger and later stage clinical trials for our product candidates and the potential commercialization of eteplirsen, we are working toincrease future manufacturing capacity and scale up production of some of the components of our drug products. In 2016, our focus remains on (i) achievinglarger-scale manufacturing capacity for eteplirsen throughout the manufacturing supply chain and (ii) continuing to increase material and API productioncapacity to provide the anticipated amounts of drug product needed for our planned studies for our product candidates. We may not be able to successfullyincrease manufacturing capacity or scale up the production of materials, APIs and drug products, whether in collaboration with third-party manufacturers oron our own, in a manner that is safe, compliant with cGMP conditions or other applicable legal or regulatory requirements or is cost-effective, or in a timeframe required to meet our timelines for clinical trials, potential commercialization and other business plans, or at all. cGMP and other quality issues mayarise during our efforts to increase manufacturing capacity and scale up production with our current or any new contract manufacturers. These issues mayarise in connection with the underlying materials, the inherent properties of a product candidate itself or the product candidate in combination with othercomponents added during the manufacturing and packaging process or during shipping and storage of the APIs or finished drug product. In addition, in orderto release product and demonstrate stability of product candidates for use in late stage clinical trials (and any subsequent drug products for commercial use),our analytical methods must be validated in accordance with regulatory guidelines. We may not be able to successfully validate, or maintain validation of,our analytical methods or demonstrate adequate purity, stability or comparability of the product candidates in a timely or cost-effective manner, or at all. Ifwe are unable to successfully validate our analytical methods or to demonstrate adequate purity, stability or comparability, the development of our productcandidates and regulatory approval or commercial launch for any resulting drug products may be delayed, which could significantly harm our business.During work with our third-party manufacturers to increase manufacturing capacity and scale up production, it is possible that they could makeimprovements in the manufacturing and scale-up processes for our product candidates. We may not own or be able to secure ownership of such improvementsor may have to share the intellectual property rights to those improvements. Additionally, it is possible that we will need additional processes, technologiesand validation studies, which could be costly and which we may not be able to develop or acquire from third parties. Any failure to secure the intellectualrights required for the manufacturing process needed for large-scale clinical trials or commercialization of our product candidates could cause significantdelays in our business plans or prevent commercialization of our product candidates.We are winding down our expired U.S. government contract, and further development of our Ebola and Marburg product candidates may be limited byour ability to obtain additional funding for these programs and by the intellectual property and other rights retained by the U.S. government.We have historically relied on U.S. government contracts and awards to fund and support certain development programs, including our Ebola andMarburg programs. The July 2010 DoD contract providing funds for our Marburg program expired in July 2014, and the Ebola portion of the contract waspreviously terminated by the DoD in 2012 for convenience of the DoD. We are currently involved in contract wind-down activities and may be subject toadditional government audits prior to collecting final cost reimbursements and fees owed by the government. If we are not able to complete such audits orother government requirements successfully, then the government may withhold some or all of the currently outstanding amounts owed to us. We mayexplore and evaluate options to continue advancing the development of our Ebola and Marburg product candidates, which may or may not include fundingthrough U.S. government programs. As a result of government budgetary cuts, appropriations and sequestration, among other reasons, the viability of thegovernment and its agencies as a partner for further development of our Ebola and Marburg programs, or other programs, is uncertain. The options for us tofurther develop product candidates that were previously developed under contracts with the U.S. government with third parties may be limited or difficult incertain respects given that, after termination or expiration of a U.S. government contract, the government has broad license rights in intellectual propertydeveloped under such contract. Therefore, the U.S. government may have the right to develop all or some parts of product candidates we have developedunder a U.S. government contract after such contract has terminated or expired.-25-We may not be able to successfully conduct clinical trials due to various process-related factors which could negatively impact our business plans.The successful start and completion of any of our clinical trials within time frames consistent with our business plans is dependent on various factors,which include, but are not limited to, our ability to: ·recruit and retain employees, consultants or contractors with the required level of expertise; ·recruit and retain sufficient patients needed to conduct a clinical trial; oparticipant enrollment and retention is a function of many factors, including the size of the relevant population, the proximity ofparticipants to clinical sites, activities of patient advocacy groups, the eligibility criteria for the trial, the existence of competingclinical trials, the availability of alternative or new treatments, side effects from the therapy, lack of efficacy, personal issues andease of participation; ·timely and effectively contract with (under reasonable terms), manage and work with investigators, institutions, hospitals and the contractresearch organizations (“CROs”) involved in the clinical trial; ·negotiate contracts and other related documents with clinical trial parties and IRBs, such as informed consents, CRO agreements and siteagreements, which can be subject to extensive negotiations that could cause significant delays in the clinical trial process. In addition, termsmay vary significantly among different trial sites and CROs and may subject the Company to various risks; ·ensure adherence to trial designs and protocols agreed upon and approved by regulatory authorities and applicable legal and regulatoryguidelines; ·manage or resolve unforeseen adverse side effects during a clinical trial; ·conduct the clinical trials in a cost effective manner, including managing foreign currency risk in clinical trials conducted in foreignjurisdictions and cost increases due to unforeseen or unexpected complications such as enrollment delays, or needing to outsource certainCompany functions during the clinical trial; and ·execute clinical trial designs and protocols approved by regulatory authorities without deficiencies.If we are not able to manage the clinical trial process successfully, our business plans could be delayed or be rendered unfeasible for us to executewithin our planned or required time frames, or at all.We have incurred operating losses since our inception and we may not achieve or sustain profitability.We incurred an operating loss of $220.2 million for the year ended December 31, 2015. Our accumulated deficit was $899.1 million as of December31, 2015. Substantially all of our revenue to date has been derived from research and development contracts with the DoD, the last of which expired in July2014. We have not yet generated any revenue from product sales and have generally incurred expenses related to research and development of ourtechnology and product candidates, from general and administrative expenses that we have incurred while building our business infrastructure. We anticipatethat our expenses will increase substantially if and as we: ·continue our research, preclinical and clinical development of our product candidates; ·respond to and satisfy requests and requirements from regulatory authorities in connection with development and potential approval of ourproduct candidates; ·initiate additional clinical trials for our product candidates; ·seek marketing approvals for our product candidates that successfully complete clinical trials; ·acquire or in-license other product candidates; ·establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; ·maintain, expand and protect our intellectual property portfolio; ·increase manufacturing capabilities including capital expenditures related to our real estate facilities and entering into manufacturingagreements; ·hire additional clinical, quality control and scientific personnel; and-26- ·add operational, financial and management information systems and personnel, including personnel to support our product development andplanned future commercialization efforts.Our ability to achieve and maintain profitability depends on various factors including our ability to raise additional capital, partner with third partiesfor one or more of our programs, complete development of our product candidates, obtain regulatory approvals and market our approved products, if any. It isuncertain when, if ever, we will become profitable and if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly orannual basis. Our failure to become and remain profitable would decrease the value of the Company and could impair our ability to raise capital, maintain ourresearch and development efforts, expand our business or continue our operations.If the FDA does not approve our eteplirsen NDA by the currently planned PDUFA date, or at all, our business may be negatively impacted and we maysuffer financial losses in connection with winding down and terminating contracts, manufacturing commitments and employees hired in connection withour current and planned activities in preparation for a potential commercial launch.Given the potential commercialization timelines, we have commenced certain pre-launch and commercialization investments and activities including,but not limited to, negotiating and entering into supply and other commercial agreements, scaling up manufacturing and hiring certain positions needed forpre-launch and commercial activities and operations. If the FDA delays or does not provide approval for our eteplirsen NDA by the currently planned PDUFAdate of May 26, 2016, or at all, or we need to delay or discontinue our development and commercialization plans for eteplirsen for other reasons, our businessand the development of our follow-on DMD product candidates may be negatively impacted and we may incur financial losses in connection with delaying,winding down or terminating the investments, contracts and commitments we enter into for the purpose of positioning ourselves for a commercial launch ofeteplirsen.We will need additional funds to conduct our planned research, development and manufacturing efforts. If we fail to attract significant capital onacceptable terms or fail to enter into strategic relationships, we may be unable to continue to develop our product candidates.We will likely require additional capital from time to time in the future in order to continue the development of product candidates in our pipeline andto expand our product portfolio. The actual amount of funds that we may need will be determined by many factors, some of which are beyond our control.These factors include the success of our research and development efforts, the status of our preclinical and clinical testing, costs and timing relating tosecuring regulatory approvals and obtaining patent rights, regulatory changes, competitive and technological developments in the market and anycommercialization expenses related to any product sales, marketing, manufacturing and distribution. An unforeseen change in these factors, or others, mightincrease our need for additional capital.We would expect to seek additional financing from the sale and issuance of equity or equity-linked or debt securities, and we cannot predict thatfinancing will be available when and as we need financing or that, if available, the financing terms will be commercially reasonable. In addition, if the FDAdelays or ultimately denies approval of our eteplirsen NDA, raising additional funds may be difficult. If we are unable to obtain additional financing whenand if we require it or on commercially reasonable terms, this would have a material adverse effect on our business and results of operations. If we are able to consummate such financings, the trading price of our common stock could be adversely affected and/or the terms of such financingsmay adversely affect the interests of our existing stockholders. To the extent we issue additional equity securities or convertible securities, our existingstockholders could experience substantial dilution in their economic and voting rights. For example, on October 9, 2015, we sold 3,250,000 shares of ourcommon stock in an underwritten public offering at a price to the public of $39.00 per share. Additional debt financing, if available, may involve agreementsthat include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaringdividends.Further, we may also enter into relationships with pharmaceutical or biotechnology companies to perform research and development with respect toour technologies, research programs, conduct clinical trials or market our product candidates. Other than preclinical collaborations with academic or researchinstitutions and government entities for the development of additional exon-skipping product candidates for the treatment of DMD and clinicalcollaboration for a product candidate for the treatment of influenza, we currently do not have a strategic relationship with a third party to perform research ordevelopment using our technologies or assist us in funding the continued development and commercialization of any of our programs or product candidates.If we were to have such a strategic relationship, such third party may require us to issue equity to such third party, relinquish valuable rights to ourtechnologies, future revenue streams, research programs or product candidates, or to grant licenses on terms that may not be favorable to us.-27-Our indebtedness resulting from our credit and security agreement with MidCap Financial could adversely affect our financial condition or restrict ourfuture operations.On June 26, 2015, the Company entered into a credit and security agreement with MidCap Financial that provides a senior secured term loan of $20.0million, which may be increased by an additional $20.0 million upon the acceptance by the FDA of the NDA for eteplirsen. This indebtedness could haveimportant consequences, including: ·requiring the Company to maintain pledged cash in favor of MidCap Financial equal to not less than the lesser of the outstanding term loans or(a) $15.0 million prior to the increase in the term loan by an additional $20.0 million and (b) $30.0 million thereafter; ·limiting our flexibility in planning for, or reacting to, changes in our business and our industry; ·placing us at a competitive disadvantage compared to our competitors who have less debt or competitors with comparable debt at morefavorable interest rates; ·limiting our ability to borrow additional amounts for working capital, capital expenditures, research and development efforts, acquisitions,debt service requirements, execution of our business strategy and other purposes; and ·resulting in an acceleration of the maturity of such term loans upon the occurrence of a material adverse change or another default under thecredit and security agreement.Any of these factors could materially and adversely affect our business, financial condition and results of operations. In addition, if we incuradditional indebtedness, the risks related to our business and our ability to service our indebtedness would increase.The estimates and judgments we make, or the assumptions on which we rely, in preparing our consolidated financial statements could prove inaccurate.Our consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States. Thepreparation of these consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of our assets, liabilities,revenues and expenses, the amounts of charges accrued by us and related disclosure of contingent assets and liabilities. Such estimates and judgmentsinclude those related to revenue recognition, accrued expenses, assumptions in the valuation of stock-based compensation and accounting for and valuationof liability classified warrants. We base our estimates on historical experience, facts and circumstances known to us and on various other assumptions that webelieve to be reasonable under the circumstances. We cannot provide assurances, however, that our estimates, or the assumptions underlying them, will notchange over time or otherwise prove inaccurate. If this is the case, we may be required to restate our consolidated financial statements, which could in turnsubject us to securities class action litigation. Defending against such potential litigation relating to a restatement of our consolidated financial statementswould be expensive and would require significant attention and resources of our management. Moreover, our insurance to cover our obligations with respectto the ultimate resolution of any such litigation may be inadequate. As a result of these factors, any such potential litigation could have a material adverseeffect on our financial results and cause our stock price to decline, which could in turn subject us to securities class action litigation.Our ability to use net operating loss carryforwards and other tax attributes to offset future taxable income may be limited as a result of future transactionsinvolving our common stock.In general, under Section 382 of the Internal Revenue Code of 1986, as amended, a corporation that undergoes an ‘‘ownership change’’ is subject tolimitations on its ability to utilize its pre-change net operating losses and certain other tax assets to offset future taxable income. In general, an ownershipchange occurs if the aggregate stock ownership of certain stockholders increases by more than 50 percentage points over such stockholders’ lowestpercentage ownership during the testing period, which is generally three years. An ownership change could limit our ability to utilize our net operating lossand tax credit carryforwards for taxable years including or following such “ownership change.” Limitations imposed on the ability to use net operating lossesand tax credits to offset future taxable income could require us to pay U.S. federal income taxes earlier than we estimated than would have otherwise beenrequired if such limitations were not in effect and could cause such net operating losses and tax credits to expire unused, in each case reducing or eliminatingthe benefit of such net operating losses and tax credits and potentially adversely affecting our financial position. Similar rules and limitations may apply forstate income tax purposes.We rely on third parties to provide services in connection with our preclinical and clinical development programs. The inadequate performance by or lossof any of these service providers could affect our product candidate development.Several third parties provide services in connection with our preclinical and clinical development programs, including in vitro and in vivo studies,assay and reagent development, immunohistochemistry, toxicology, pharmacokinetics, clinical assessments, data-28-monitoring and management, statistical analysis and other outsourced activities. If these service providers do not adequately perform the services for whichwe have contracted or cease to continue operations and we are not able to quickly find a replacement provider or we lose information or items associated withour product candidates, our development programs may be delayed.If we fail to retain our key personnel or are unable to attract and retain additional qualified personnel, our future growth and our ability to compete wouldsuffer.We are highly dependent on the efforts and abilities of the principal members of our senior management. Additionally, we have scientific personnelwith significant and unique expertise in RNA-targeted therapeutics and related technologies. The loss of the services of any one of the principal members ofour managerial team or staff may prevent us from achieving our business objectives.Our former CEO and President resigned on March 31, 2015 and we have appointed an interim CEO. No assurance can be made about the impact thatthis change in management will have on the Company and its business plans (including our regulatory and clinical plans and relationships) nor as to whenwe will hire a permanent CEO. The existing management team is actively managing the business in accordance with a business strategy approved by theboard of directors.The competition for qualified personnel in the biotechnology field is intense, and our future success depends upon our ability to attract, retain andmotivate such personnel. In order to develop and commercialize our products successfully, we will be required to retain key management and scientificemployees. In certain instances, we may also need to expand or replace our workforce and our management ranks. In addition, we rely on certain consultantsand advisors, including scientific and clinical advisors, to assist us in the formulation and advancement of our research and development programs. Ourconsultants and advisors may be employed by other entities or have commitments under consulting or advisory contracts with third parties that limit theiravailability to us, or both. If we are unable to attract, assimilate or retain such key personnel, our ability to advance our programs would be adversely affected.If we are unable to effectively manage our growth, execute our business strategy and implement compliance controls and systems, the trading price of ourcommon stock could decline. Any failure to establish and maintain effective internal control over financial reporting could adversely affect investorconfidence in our reported financial information.We anticipate continued growth in our business operations due, in part, to advancing our product candidates. This future growth could create a strainon our organizational, administrative and operational infrastructure. Our ability to manage our growth properly and maintain compliance with all applicablerules and regulations will require us to continue to improve our operational, legal, financial and management controls, as well as our reporting systems andprocedures. We may not be able to build the management and human resources and infrastructure necessary to support the growth of our business. The timeand resources required to implement systems and infrastructure that may be needed to support our growth is uncertain, and failure to completeimplementation in a timely and efficient manner could adversely affect our operations.We may engage in future acquisitions or collaborations with other entities that increase our capital requirements, dilute our stockholders, cause us toincur debt or assume contingent liabilities and subject us to other risks.We actively evaluate various strategic transactions on an ongoing basis, including licensing or acquiring complementary products, technologies orbusinesses. Potential acquisitions or collaborations with other entities may entail numerous risks, including increased operating expenses and cashrequirements, assimilation of operations and products, retention of key employees, diversion of our management’s attention and uncertainties in our abilityto maintain key business relationships of the acquired entities. In addition, if we undertake acquisitions, we may issue dilutive securities, assume or incurdebt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense.Our success, competitive position and future revenue, if any, depend in part on our ability and the abilities of our licensors to obtain and maintain patentprotection for our technologies and product candidates, to preserve our trade secrets, to prevent third parties from infringing on our proprietary rights andto operate without infringing on the proprietary rights of third parties.We currently hold various issued patents and exclusive rights to issued patents and own and have licenses to various patent applications, in each casein the United States as well as other countries. We anticipate filing additional patent applications both in the United States and in other countries. The patentprocess, however, is subject to numerous risks and uncertainties, and we can provide no assurance that we will be successful in obtaining and defendingpatents or in avoiding infringement of the rights of others. Even when our patent claims are allowed, the claims may not issue, or in the event of issuance,may not be sufficient to protect the technology owned by or licensed to us or our collaborators. Even if our patents and patent applications do provide ourproduct candidates and platform technology with a basis for exclusivity, we and our collaborators may not be able to develop or commercialize such productcandidates or platform technology due to patent positions held by one or more third parties.-29-We may not be able to obtain and maintain patent protection for our product candidates necessary to prevent competitors from commercializingcompeting product candidates. Our patent rights might be challenged, invalidated, circumvented or otherwise not provide any competitive advantage, andwe might not be successful in challenging the patent rights of our competitors through litigation or administrative proceedings. For example, in July 2014,the Patent Trial and Appeal Board (the “PTAB”) of the USPTO declared patent interferences between certain patents held by Sarepta (under license from theUniversity of Western Australia, “UWA”) and patent applications held by BioMarin (under license from Academisch Ziekenhuis Leiden, “AZL”) related toexon 51 and exon 53 skipping therapies designed to treat DMD. In particular, the PTAB declared Interference No. 106,008, which identifies Sarepta’s/UWA’sU.S. Patent Nos. 7,807,816 and 7,960,541, both covering eteplirsen, as interfering with BioMarin’s/AZL’s U.S. Application No. 13/550,210. The PTAB alsodeclared Interference No. 106,007, which identifies Sarepta’s/UWA’s U.S. Patent No. 8,455,636, covering SRP-4053, as interfering with BioMarin’s/AZL’sU.S. Application No. 11/233,495. In September 2014, the PTAB declared a third patent interference relating to certain methods concerning the exon 51skipping therapies that are the subject of Interference No. 106,008. In particular, the PTAB declared Interference No. 106,013, which identifiesSarepta’s/UWA’s U.S. Patent No. 8,486,907, which covers certain methods of using eteplirsen, as interfering with BioMarin’s/AZL’s U.S. ApplicationNo. 14/198,992. In addition, in a September 2014 Order in Interference No. 106,007, the PTAB authorized us to file a motion with the PTAB, which we filedin November 2014, requesting the declaration of a fourth interference relating to certain methods concerning the exon 53 skipping therapies that are thesubject of Interference No. 106,007, including SRP-4053, and between Sarepta’s/UWA’s U.S. Patent No. 8,455,636 and BioMarin’s/AZL’s U.S. ApplicationNo. 14/248,279. On September 29, 2015, we received notice that the PTAB had issued a decision in Interference No. 106,013 that resulted in a judgmentagainst Sarepta and an order for the cancellation of Sarepta’s/UWA’s U.S. Patent No. 8,486,907 that covers certain methods of using eteplirsen therebyleaving open the possibility of BioMarin’s/AZL’s competing U.S. Application No. 14/198,992 to issue and, if so, potentially provide a basis for BioMarin toallege that our product candidate, eteplirsen, infringes a patent granting from this application. We filed a Request for Rehearing that requests the PTAB tocontinue this interference, and the PTAB denied our Request on December 29, 2015. We intend to appeal this decision to an appropriate appeals court. Wecannot make any assurances about the outcome of the two remaining proceedings (Interference No. 106,007 and Interference No. 106,008) or appeals of anyof these three interferences. Any additional adverse rulings, which, in the case of Interference No. 106,007 and Interference No. 106,008 could come at anytime and, if negative, could adversely affect our business and result in a decline in our stock price. If final resolution of the interferences and related appealsare not in our favor, then the Sarepta/UWA patents involved in these interferences and any other Sarepta/UWA patents or applications also found to beinterfering may be invalidated, and as a result, we may not have any patent-based exclusivity available for our product candidates, which may have a materialnegative impact on our business plans. In addition, if final resolution of the interferences or related appeals are not in our favor, the USPTO may issue theBioMarin/AZL patent applications resulting in the grant of one or more patents that may provide a basis for BioMarin to allege that our product candidates,eteplirsen and/or SRP-4053, infringe such patents. In addition, these interferences, appeals and any subsequent litigation may require significant financialresources that we may have planned to spend on other Company objectives, resulting in delays or other negative impacts on such other objectives. Inaddition, BioMarin may continue to evaluate other opportunities to challenge our intellectual property rights or seek to broaden their patent positions in anattempt to cover our product candidates in the United States and in other jurisdictions. We are also aware of certain pending and granted claims that are heldby BioMarin in Japan, Europe and certain other countries that may provide the basis for BioMarin or other parties to assert that eteplirsen infringes on suchclaims. Because we have not yet initiated an invalidation proceeding in these countries, the outcome and timing of any such proceeding cannot be predictedor determined as of the date of this report.As a matter of public policy, there might be significant pressure on governmental bodies to limit the scope of patent protection or impose compulsorylicenses for disease treatments that prove successful. Additionally, jurisdictions other than the United States might have less restrictive patent laws than theUnited States, giving foreign competitors the ability to exploit these laws to create, develop and market competing products. The USPTO and patent officesin other jurisdictions have often required that patent applications concerning pharmaceutical and/or biotechnology-related inventions be limited or narrowedsubstantially to cover only the specific innovations exemplified in the patent application, thereby limiting the scope of protection against competitivechallenges. Accordingly, even if we or our licensors are able to obtain patents, the patents might be substantially narrower than anticipated.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 numberof significant changes to U.S. patent law, including provisions that affect the way patent applications will be prosecuted, and may also affect patentlitigation. The USPTO has issued regulations and procedures to govern administration of the Leahy-Smith Act, but many of the substantive changes to patentlaw associated with the Leahy-Smith Act have only recently become effective. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will haveon the operation of our business. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding theprosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our businessand financial condition. For instance, a third party may petition the PTAB seeking to challenge the validity of some or all of the claims in any of our patentsthrough an Inter Partes Review (“IPR”) or other post-grant proceeding. Should the PTAB institute an IPR (or other) proceeding and decide that some or all ofthe claims in the challenged patent are invalid, such a decision, if upheld on appeal, could have a material adverse effect on our business and financialcondition.The full impact of several recent U.S. Supreme Court decisions relating to patent law is not yet known. For example, on March 20, 2012, in MayoCollaborative Services, DBA Mayo Medical Laboratories, et al. v. Prometheus Laboratories, Inc., the Court-30-held that several claims drawn to measuring drug metabolite levels from patient samples and correlating them to drug doses were not patentable subjectmatter. The decision appears to impact diagnostics patents that merely apply a law of nature via a series of routine steps and it has created uncertainty aroundthe ability to patent certain biomarker-related method claims. Additionally, on June 13, 2013, in Association for Molecular Pathology v. Myriad Genetics,Inc., the Court held that claims to isolated genomic DNA are not patentable, but claims to complementary DNA molecules were held to be valid. The effect ofthe decision on patents for other isolated natural products is uncertain and, as with the Leahy-Smith Act, these decisions could increase the uncertainties andcosts surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverseeffect on our business and financial condition.Our business prospects will be impaired if third parties successfully assert that our product candidates or technologies infringe proprietary rights of suchthird parties.Our competitors may make significant investments in competing technologies, and might have or obtain patents that limit, interfere with or eliminateour ability to make, use and sell our product candidates in important commercial markets.If our product candidates or technologies infringe enforceable proprietary rights of others, we could incur substantial costs and may have to: ·obtain rights or licenses from others, which might not be available on commercially reasonable terms or at all; ·abandon development of an infringing product candidate; ·redesign product candidates or processes to avoid infringement; ·pay damages; and/or ·defend litigation or administrative proceedings which might be costly whether we win or lose, and which could result in a substantial diversionof financial and management resources.Any of these events could substantially harm our potential earnings, financial condition and operations. BioMarin, which is developing competitivepipeline products, has rights to patent claims that, absent a license, may preclude us from commercializing eteplirsen in several jurisdictions. BioMarin hasrights to European Patent No. EP 1619249, for example. We opposed this patent in the Opposition Division of the European Patent Office (“EPO”), and theOpposition Division maintained certain claims of this patent relating to the treatment of DMD by skipping dystrophin exons 51 and 46, which may provide abasis to maintain that commercialization of eteplirsen in a European country where BioMarin has a patent corresponding to EP 1619249 would infringe onsuch patent. Both we and BioMarin have appealed the Opposition Division decision, submitted briefs in support of our respective positions and have alsosubmitted responses to each other’s briefs. BioMarin filed arguments with the EPO in response to Sarepta’s previously filed briefs. The Opposition Divisiondecision, if maintained at the appeals level, could have a substantial negative effect on our business and leaves open the possibility that BioMarin or otherparties that have rights to such patent could assert that our product candidate, eteplirsen, infringes on such patent in a relevant European country. The timingand outcome of the appeal cannot be predicted or determined as of the date of this report. If as part of any appeal before the European Patent Office we areunsuccessful in invalidating BioMarin’s claims that were maintained by the Opposition Division or if claims previously invalidated by the OppositionDivision are restored on appeal, our ability to commercialize both eteplirsen and other therapeutic candidates could be materially impaired. Moreover, ourability to commercialize eteplirsen in a European country where BioMarin has a patent related to EP 1619249 while the appeal process remains ongoingbefore the European Patent Office Board of Appeals could be materially impaired. In addition, we are aware of various divisional applications relating to EP1619249 that are being pursued by BioMarin, which are pending and in some cases are proceeding to grant. Should any patents grant from theseapplications, our ability to commercialize eteplirsen or our other therapeutic candidates, such as SRP-4045 and SRP-4053, could be materially impaired.We are also aware of existing patent claims BioMarin is pursuing in the United States, including those involved in the interferences declared by theUSPTO in July 2014 and September 2014 and discussed in these risk factors, and others that it has or is pursuing in other countries, that where granted mayprovide the basis for BioMarin or other parties to assert that commercialization of eteplirsen and certain other of our product candidates would infringe onsuch claims.The DMD patent landscape is continually evolving and multiple parties, including both commercial entities and academic institutions, may haverights to claims or may be pursuing additional claims that could provide these parties a basis to assert that our product candidates infringe on the intellectualproperty rights of such parties. Similarly, we may be able to assert that certain activities engaged in by these parties infringe on our current or future patentrights. There has been, and we believe that there will continue to be, significant litigation in the biopharmaceutical and pharmaceutical industries regardingpatent and other intellectual property rights. We also cannot be certain that other third parties will not assert patent infringement in the future with respect toany of our development programs.-31-We face intense competition and rapid technological change, which may result in other companies discovering, developing or commercializingcompetitive products.The biotechnology and pharmaceutical industries are highly competitive and subject to significant and rapid technological change. We are aware ofmany pharmaceutical and biotechnology companies that are actively engaged in research and development in areas related to antisense technology and otherRNA technologies, or that are developing alternative approaches to or therapeutics for the disease indications on which we are focused. Some of thesecompetitors are developing or testing product candidates that now, or may in the future, compete directly with our product candidates. For example, webelieve that companies including Alnylam Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc. (formerly Isis Pharmaceuticals, Inc.), Roche Innovation CenterCopenhagen (formerly Santaris Pharma A/S) and Nippon Shinyaku Co. Ltd. share a focus on RNA-targeted drug discovery and development. Competitorswith respect to our exon-skipping DMD program, or eteplirsen, include BioMarin (which acquired Prosensa), Nippon Shinyaku, Daiichi Sankyo and Shireplc; and other companies such as PTC Therapeutics and Summit plc have also been working on DMD programs. Additionally, several companies haveentered into collaborations or other agreements for the development of product candidates, including mRNA, gene (CRIPSR and AAV, among others) andsmall molecule therapies that are potential competitors for therapies being developed in the muscular dystrophy, neuromuscular and rare disease space,including, but not limited to, Pfizer, Inc., Bristol-Myers Squibb, Biogen Idec, Inc., Ionis Pharmaceuticals, Inc., Alexion Pharmaceuticals, Inc., Sanofi, EliLilly, Alnylam, Moderna Therapeutics, Inc., Summit plc, Akashi, Catabasis, and Oxford University. Although BioMarin received a complete response letterfor KyndrisaTM (drisapersen) for the treatment of DMD amenable to exon 51 skipping on January 14, 2016, BioMarin continues to be a competitor for us onthe development of DMD exon-skipping product candidates. BioMarin announced that its ongoing Kyndrisa extension studies will continue, as will theongoing clinical trials for other exon-skipping oligonucleotides, BMN 044, BMN 045 and BMN 053, while BioMarin is exploring next steps for thisapplication. If BioMarin is successful in obtaining regulatory approval for any of its exon-skipping product candidates, it may limit our ability to gain orkeep market share in the DMD space or other diseases targeted by our exon-skipping platform and product candidate pipeline.It is possible that our competitors will succeed in developing technologies that limit the market size for our product candidates, impact the regulatoryapproval process for our product candidates that are more effective than our product candidates or that would render our technology obsolete ornoncompetitive. Our competitors, including BioMarin, may, among other things: ·develop safer or more effective products; ·implement more effective approaches to sales and marketing; ·develop less costly products; ·obtain regulatory approval more quickly; ·have access to more manufacturing capacity; ·develop products that are more convenient and easier to administer; ·form more advantageous strategic alliances; or ·establish superior intellectual property positions.We may be subject to product liability claims and our insurance may not be adequate to cover damages.We currently have no products that have been approved for commercial sale; however, the current and future use of our product candidates by us andour collaborators in clinical trials, expanded access programs, the sale of any products in the future, or the use of our products under emergency use vehiclesmay expose us to liability claims inherent to the manufacture, clinical testing, marketing and sale of medical products. These claims might be made directlyby consumers or healthcare providers or indirectly by pharmaceutical companies, our collaborators or others selling such products. Regardless of merit oreventual outcome, we may experience financial losses in the future due to such product liability claims. We have obtained limited general commercialliability insurance coverage for our clinical trials. We intend to expand our insurance coverage to include the sale of commercial products if we obtainmarketing approval for any of our product candidates. However, we may not be able to maintain insurance coverage at a reasonable cost or in sufficientamounts to protect us against all losses. If a successful product liability claim or series of claims is brought against us for uninsured liabilities or in excess ofinsured liabilities, our assets may not be sufficient to cover such claims and our business operations could be impaired.Our operations involve the use of hazardous materials, and we must comply with environmental laws, which can be expensive, and may affect our businessand operating results.Our research and development activities involve the use of hazardous materials, including organic and inorganic solvents and reagents. Accordingly,we are subject to federal, state and local laws and regulations governing the use, storage, handling, manufacturing, exposure to and disposal of thesehazardous materials. In addition, we are subject to environmental, health and-32-workplace safety laws and regulations, including those governing laboratory procedures, exposure to blood-borne pathogens and the handling of bio-hazardous materials. Although we believe that our activities conform in all material respects with such environmental laws, there can be no assurance thatviolations of these laws will not occur in the future as a result of human error, accident, equipment failure or other causes. Liability under environmental,health and safety laws can be joint and several and without regard to fault or negligence. The failure to comply with past, present or future laws could resultin the imposition of substantial fines and penalties, remediation costs, property damage and personal injury claims, loss of permits or a cessation ofoperations, and any of these events could harm our business and financial condition. We expect that our operations will be affected by other newenvironmental, health and workplace safety laws on an ongoing basis, and although we cannot predict the ultimate impact of any such new laws, they mayimpose greater compliance costs or result in increased risks or penalties, which could harm our business.We rely significantly on information technology and any failure, inadequacy, interruption or security lapse of that technology, including any cybersecurity incidents, could harm our ability to operate our business effectively.Despite the implementation of security measures, our internal computer systems and those of third parties with which we contract are vulnerable todamage from cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. Systemfailures, accidents or security breaches could cause interruptions in our operations, and could result in a material disruption of our clinical activities andbusiness operations, in addition to possibly requiring substantial expenditures of resources to remedy. The loss of clinical trial data could result in delays inour regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach wereto result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur a liabilityand our research and development programs and the development of our product candidates could be delayed.We may incur substantial costs in connection with litigation and other disputes.In the ordinary course of business we may, and in some cases have, become involved in lawsuits and other disputes such as securities claims,intellectual property challenges, including interferences declared by the USPTO, and employee matters. It is possible that we may not prevail in claims madeagainst us in such disputes even after expending significant amounts of money and company resources in defending our positions in such lawsuits anddisputes. The outcome of such lawsuits and disputes is inherently uncertain and may have a negative impact on our business, financial condition and resultsof operations.Risks Related to Our Common StockOur stock price is volatile and may fluctuate due to factors beyond our control.The market prices for and trading volumes of securities of biotechnology companies, including our securities, has historically been volatile. Our stockhas had significant swings in trading prices, in particular in connection with our public communications regarding feedback received from regulatoryauthorities. For example, over the last twelve months, our stock has increased as much as 60% in a single day or decreased as much as 55% in a single day.We expect that our stock could have a material swing in its trading price in connection with competitor developments, any advisory committeemeeting/recommendation or FDA decision relating to our eteplirsen NDA, including a decline in trading price if research analysts, investors or others whofollow us view the results of any developments related to these events as negative for Sarepta. The market has from time to time experienced significant priceand volume fluctuations unrelated to the operating performance of particular companies. The market price of our common stock may fluctuate significantlydue to a variety of factors, including but not limited to: ·discussions at, the outcome of and other matters related to the advisory committee meeting for eteplirsen; ·the timing of our submissions to regulatory authorities and regulatory decisions and developments including any decision by the FDAregarding our NDA for eteplirsen; ·positive or negative clinical trial results or regulatory interpretations of data collected in clinical trials conducted by us, our strategic partners,our competitors or other companies with investigational drugs targeting the same, similar or related diseases to those targeted by our productcandidates; ·delays in beginning and completing preclinical and clinical studies for potential product candidates; ·delays in entering or failing to enter into strategic relationships with respect to development and/or commercialization of our productcandidates or entry into strategic relationships on terms that are not deemed to be favorable to our Company; ·technological innovations, product development or commercial product introductions by ourselves or competitors; ·changes in applicable government regulations or regulatory requirements in the approval process;-33- ·developments concerning proprietary rights, including patents and patent litigation matters, such as developments in the interferences declaredby the USPTO, including in the near term any outcomes of ongoing interference proceedings and over the longer term the outcomes from anyrelated appeals; ·public concern relating to the commercial value, efficacy or safety of any of our products; ·our ability to obtain funds, through the issuance of equity or equity linked securities or incurrence of debt, or other corporate transactions; ·comments by securities analysts; ·developments in litigation such as the stockholder lawsuits against us; ·changes in senior management such as the resignation of our former CEO and appointment of an interim CEO in 2015; or ·general market conditions in our industry or in the economy as a whole.Broad market and industry factors may seriously affect the market price of a company’s stock, including ours, regardless of actual operatingperformance. In addition, in the past, following periods of volatility in the overall market and the market price of a particular company’s securities, securitiesclass action litigation has often been instituted against these companies. Such litigation could result in substantial costs and a diversion of our management’sattention and resources.Provisions of our certificate of incorporation, bylaws and Delaware law might deter acquisition bids for us that might be considered favorable and preventor frustrate any attempt to replace or remove the then-current management and board of directors.Certain provisions of our certificate of incorporation and bylaws may make it more difficult for a third party to acquire control of us or effect a changein our board of directors and management. These provisions include: ·when the board is comprised of six or more directors, classification of our board of directors into two classes, with one class elected each year; ·directors may only be removed for cause by the affirmative vote of majority of the voting power of all the then-outstanding shares of votingstock; ·prohibition of cumulative voting of shares in the election of directors; ·right of the board of directors to elect directors to fill a vacancy created by the expansion of the board of directors or the resignation, death,disqualification or removal of a director; ·express authorization of the board of directors to make, alter or repeal our bylaws; ·prohibition on stockholder action by written consent; ·advance notice requirements for nominations for election to our board or for proposing matters that can be acted upon by stockholders atstockholder meetings; ·the ability of our board of directors to authorize the issuance of undesignated preferred stock, the terms and rights of which may be establishedand shares of which may be issued without stockholder approval, including rights superior to the rights of the holders of common stock; and ·a super-majority (66 2/3%) of the voting power of all of the then-outstanding shares of capital stock are required to amend, rescind, alter orrepeal our bylaws and certain provisions of our certificate of incorporation.In addition, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which may prohibit certain businesscombinations with stockholders owning 15% or more of our outstanding voting stock. These and other provisions in our certificate of incorporation and ourbylaws and in the Delaware General Corporation Law could make it more difficult for stockholders or potential acquirers to obtain control of our board ofdirectors or initiate actions that are opposed by the then-current board of directors.We expect our operating results to fluctuate in future periods, which may adversely affect our stock price.Our quarterly operating results have fluctuated in the past, and we believe they will continue to do so in the future. Our operating results may fluctuatedue to the variable nature of our revenue and research and development expenses. Likewise, our research and development expenses may experiencefluctuations as a result of the timing and magnitude of expenditures incurred in-34-support of our DMD and other proprietary drug development programs. In one or more future periods, our results of operations may fall below theexpectations of securities analysts and investors. In that event, the market price of our common stock could decline.A significant number of shares of our common stock are issuable pursuant to outstanding stock awards, and we expect to issue additional stock awardsand shares of common stock in the future. Exercise of these awards and sales of shares will dilute the interests of existing security holders and may depressthe price of our common stock.As of December 31, 2015, there were approximately 45.6 million shares of common stock outstanding and outstanding awards to purchase 6.8 millionshares of common stock under various incentive stock plans. Additionally, as of December 31, 2015, there were 1.8 million shares of common stock availablefor future issuance under our Amended and Restated 2011 Equity Incentive Plan, 0.1 million shares of common stock available for issuance under our 2013Employee Stock Purchase Plan and 1.0 million shares of common stock available for issuance under our 2014 Employment Commencement Incentive Plan.We may issue additional common stock and warrants from time to time to finance our operations. We may also issue additional shares to fund potentialacquisitions or in connection with additional stock options or other equity awards granted to our employees, officers, directors and consultants under ourAmended and Restated 2011 Equity Incentive Plan, our 2013 Employee Stock Purchase Plan or our 2014 Employment Commencement Incentive Plan. Theissuance of additional shares of common stock or warrants to purchase common stock and the perception that such issuances may occur or exercise ofoutstanding warrants or options may have a dilutive impact on other stockholders and could have a material negative effect on the market price of ourcommon stock. Item 1B. Unresolved Staff Comments.None. Item 2. Properties.A description of the facilities we own and/or occupy is included in the following table. We believe that our current facilities in Cambridge,Massachusetts, Andover, Massachusetts and Corvallis, Oregon are suitable and will provide sufficient capacity to meet the projected needs of our business forthe next 12 months. Except as noted below, all of our properties are currently being used in the operation of our business. Location of Property SquareFootage LeaseExpirationDate Purpose OtherInformation215 First Street, Cambridge, MA 02142 88,329 January – February2021 Laboratory and office space Corporate headquarters100 Federal Street, Andover, MA 60,000 N/A – facility is owned Manufacturing and office space Primarily manufacturingspace**4575 SW Research Way, Suite 200,Corvallis, OR 97333 53,000 December 2020 Laboratory and office space Primarily lab space1749 SW Airport Avenue, Corvallis, OR97333 36,150 N/A – facility isowned; land leaseexpires February 2042 Acquired with intention ofproviding future expansion spacefor the manufacture of potentialproducts and components Approximately 25,000square feet leased and theremaining spaceunoccupied* *In November 2011, the tenant, Perpetua Power Source Technologies, Inc. (“Perpetua”), agreed to lease approximately 25,000 square feet of thebuilding until March 2017. Perpetua has the option to extend the lease for an additional year if notice is provided no less than 12 months prior to theexpiration date. Perpetua also has a right of first refusal relating to the lease of the remaining space at the building and was granted an option topurchase the building during the term of the lease, provided there is no uncured default by Perpetua at the time of exercise. If the purchase option isexercised, the price for the building was $2.0 million until February 2015 and $2.1 million from March 2015 until February 2016, and will be$2.2 million from March 2016 through the remainder of the initial lease term. If Perpetua exercises its extension option, the purchase price will be$2.3 million during the term of the extension.**Currently, this facility is not ready for use. -35-Item 3. Legal Proceedings. In the normal course of business, the Company may from time to time be named as a party to various legal claims, actions and complaints,including matters involving securities, employment, intellectual property, effects from the use of therapeutics utilizing its technology, or others. For example,purported class action complaints were filed against the Company and certain of its officers in the U.S. District Court for the District of Massachusetts onJanuary 27, 2014 and January 29, 2014. The complaints were consolidated into a single action (Corban v. Sarepta, et. al., No. 14-cv-10201) by order of thecourt on June 23, 2014, and plaintiffs were afforded 28 days to file a consolidated amended complaint. The plaintiffs’ consolidated amended complaint, filedon July 21, 2014, sought to bring claims on behalf of themselves and persons or entities that purchased or acquired securities of the Company between July10, 2013 and November 11, 2013. The consolidated amended complaint alleged that Sarepta and certain of its officers violated the federal securities laws inconnection with disclosures related to eteplirsen, the Company’s lead therapeutic candidate for DMD, and seeks damages in an unspecified amount. Pursuantto the court’s June 23, 2014 order, Sarepta filed a motion to dismiss the consolidated amended complaint on August 18, 2014, and argument on the motionwas held on March 12, 2015. On March 31, 2015, the Court dismissed plaintiffs’ amended complaint. On April 30, 2015, plaintiffs in the Corban suit filed amotion for leave seeking to file a further amended complaint, which the Company opposed. Following a hearing on August 12, 2015, the Court denied thismotion, and on September 22, 2015, the Court dismissed the case. The plaintiffs filed a Notice of Appeal in the Court of Appeals for the First Circuit onSeptember 29, 2015. On January 27, 2016, the plaintiffs filed a motion to vacate the District Court’s order denying leave to amend and dismissing thecase. Defendants filed their opposition with the District Court on February 11, 2016, and oral argument on the plaintiffs’ motion was held on February 25,2016. The plaintiffs’ appellate brief is due to the First Circuit on March 22, 2016. Another complaint was filed in the U.S. District Court for the District of Massachusetts on December 3, 2014 by William Kader, Individually andon Behalf of All Others Similarly Situated v. Sarepta Therapeutics Inc., Christopher Garabedian, and Sandesh Mahatme (Kader v. Sarepta et.al 1:14-cv-14318), asserting violations of Section 10(b) of the Exchange Act and Securities and Exchange Commission Rule 10b-5 against the Company, ChristopherGarabedian and Sandesh Mahatme. Plaintiffs’ amended complaint, filed on March 20, 2015, alleges that the defendants made material misrepresentations oromissions during the putative class period of April 21, 2014 through October 27, 2014, regarding the sufficiency of the Company’s data for submission of anew drug application (“NDA”) for eteplirsen and the likelihood of the Food and Drug Administration (“FDA”) accepting the NDA based on that data.Plaintiffs seek compensatory damages and fees. The Company received service of the complaint on January 5, 2015. Sarepta filed a motion to dismiss thecomplaint on May 11, 2015, pursuant to the scheduling order entered on February 20, 2015, which plaintiffs have opposed. Oral argument on the motion hasbeen scheduled for March 2, 2016. In addition, two derivative suits were filed based upon the Company’s disclosures related to eteplirsen. On February 5, 2015, a derivative suit wasfiled against the Company’s Board of Directors in the 215th Judicial District of Harris County, Texas (David Smith, derivatively on behalf of SareptaTherapeutics, Inc., v. Christopher Garabedian et. al, Case No. 2015-06645). The claims allege that Sarepta’s directors caused Sarepta to disseminate materiallyfalse and/or misleading statements in connection with disclosures concerning the Company’s submission of the NDA for eteplirsen. Plaintiff seeksunspecified compensatory damages, actions to reform and improve corporate governance and internal procedures, disgorgement of profits, benefits and othercompensation obtained by the directors, and attorneys’ fees. On March 24, 2015, the parties agreed to abate the case pending the resolution of both suitspending in federal court in the District of Massachusetts, Corban and Kader. Additionally, on February 24, 2015, a derivative suit was filed against theCompany’s Board of Directors with the Court of Chancery of the State of Delaware (Ira Gaines, and the Ira J. Gaines Revocable Trust U/A, on behalf ofnominal defendant Sarepta Therapeutics, Inc., vs. Goolsbee et. al., No. 10713). The claims allege that the defendants participated in making materialmisrepresentations or omissions during the period of April 21, 2014 through October 27, 2014, regarding the sufficiency of the Company’s data forsubmission of the NDA for eteplirsen and the likelihood of the FDA accepting the NDA based on that data. Plaintiffs seek unspecified compensatorydamages, punitive damages, actions to reform and improve corporate governance and internal procedures, and attorneys’ fees. On March 26, 2015, the partiesagreed to stay the case pending the resolution of Kader, pending in federal court in the District of Massachusetts. Additionally, on September 23, 2014, a derivative suit was filed against the Company’s Board of Directors with the Court of Chancery of the Stateof Delaware (Terry McDonald, derivatively on behalf of Sarepta Therapeutics, Inc., et. al vs. Goolsbee et. al., No. 10157). The claims allege, among otherthings, that (i) the Company’s non-employee directors paid themselves excessive compensation fees for 2013, (ii) that the compensation for the Company’sformer CEO, Christopher Garabedian, was also excessive and such fees were the basis for Mr. Garabedian’s not objecting to or stopping the excessive fees forthe non-employee directors and (iii) that the disclosure in the 2013 proxy statement was deficient. The relief sought, among others, includes disgorgementand rescindment of allegedly excessive or unfair payments and equity grants to Mr. Garabedian and the directors, unspecified damages plus interest, adeclaration that the Company’s Amended and Restated 2011 Equity Plan at the 2013 annual meeting was ineffective and a revote for approved amendments,correction of misleading disclosures and plaintiff’s attorney fees. We have reached an agreement in principle with the parties in the McDonald suit and do notbelieve that disposition of the McDonald suit should have a material financial impact on the Company. -36-Item 4. Mine Safety Disclosures.Not applicable. -37-PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.Market InformationOur Common Stock is quoted on The NASDAQ Global Select Market under the symbol “SRPT.” Prior to January 2, 2014, our Common Stock wasquoted on The NASDAQ Global Market. The following table sets forth the high and low intraday sales prices as reported by The NASDAQ Global SelectMarket for each quarterly period in the two most recent years: High Low Year Ended December 31, 2015 First Quarter $15.74 $11.33 Second Quarter $33.16 $12.01 Third Quarter $41.47 $28.19 Fourth Quarter $41.97 $23.09 Year Ended December 31, 2014 First Quarter $31.28 $17.50 Second Quarter $40.00 $20.89 Third Quarter $31.35 $18.59 Fourth Quarter $24.95 $12.58 HoldersAs of February 19, 2016, we had 240 stockholders of record of our common stock.DividendsWe did not declare or pay cash dividends on our common stock in 2015, 2014 or 2013. We currently expect to retain future earnings, if any, to financethe operation and expansion of our business, and we do not anticipate paying any cash dividends in the foreseeable future. Any future determination relatedto our dividend policy will be made at the discretion of our board of directors.Performance GraphThe following graph compares the performance of our Common Stock for the periods indicated with the performance of the NASDAQ CompositeIndex, NASDAQ Biotechnology Index and the NYSE ARCA Biotechnology Index. This graph assumes an investment of $100 on December 31, 2010 in eachof our common stock, the NASDAQ Composite Index, NASDAQ Biotechnology Index and the NYSE ARCA Biotechnology Index, and assumes reinvestmentof dividends, if any. The stock price performance shown on the graph below is not necessarily indicative of future stock price performance. This graph is not“soliciting material,” is not deemed “filed” with the U.S. Securities and Exchange Commission and is not to be incorporated by reference into any of ourfilings under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the date hereof andirrespective of any general incorporation language in any such filing.-38-Recent Sales of Unregistered Securities.None.Purchases of Equity Securities by the Issuer and Affiliated Purchasers.None. Item 6. Selected Financial Data.The following selected financial data are derived from our consolidated financial statements and should be read in conjunction with, and is qualifiedin its entirety by, Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations, and Item 8, Financial Statements andSupplementary Data. For the Year Ended December 31, 2015 2014 2013 2012 2011 (in thousands, except per share amounts) Operations data: Revenue $1,253 $9,757 $14,219 $37,329 $46,990 Research and development 146,394 94,231 72,909 52,402 66,862 General and administrative 75,043 49,315 31,594 14,630 16,055 Operating loss (220,184) (133,789) (90,284) (29,703) (35,927)Interest income and other, net 154 779 326 354 587 (Loss) gain on change in warrant valuation — (2,779) (22,027) (91,938) 33,022 Net loss $(220,030) $(135,789) $(111,985) $(121,287) $(2,318)Net loss per share—basic and diluted $(5.20) $(3.39) $(3.31) $(5.14) $(0.11)Balance sheet data: Cash and cash equivalents $80,304 $73,551 $256,965 $187,661 $39,904 Working capital 162,249 210,929 234,840 115,022 24,583 Total assets 273,782 295,033 291,569 204,993 54,368 Stockholders’ equity 190,347 247,653 247,192 123,679 31,017 -39-Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our consolidatedfinancial statements and related notes included elsewhere in this Annual Report on Form 10-K. This discussion contains forward-looking statements thatinvolve risks and uncertainties. Please review our legend titled “Forward-Looking Information” at the beginning of this Annual Report on Form 10-Kwhich is incorporated herein by reference. Our actual results could differ materially from those discussed below. Factors that could cause or contribute tosuch differences include, but are not limited to, those identified below, and those discussed in the section titled “Risk Factors” included elsewhere in thisAnnual Report on Form 10-K. Throughout this discussion, unless the context specifies or implies otherwise, the terms “Sarepta”, “we”, “us” and “our” referto Sarepta Therapeutics, Inc. and its subsidiaries.OverviewWe are a biopharmaceutical company focused on the discovery and development of unique RNA-targeted therapeutics for the treatment of rare,infectious and other diseases. Applying our proprietary, highly-differentiated and innovative platform technologies, we are able to target a broad range ofdiseases and disorders through distinct RNA-targeted mechanisms of action. We are primarily focused on rapidly advancing the development of ourpotentially disease-modifying Duchenne muscular dystrophy (“DMD”) drug candidates, including our lead DMD product candidate, eteplirsen, designed toskip exon 51. We are also developing therapeutics using our technology for the treatment of drug resistant bacteria and infectious, rare and other humandiseases.Our RNA-targeted technologies work at the most fundamental level of biology and potentially could have a meaningful impact across a broad rangeof human diseases and disorders. Our lead program focuses on the development of disease-modifying therapeutic candidates for DMD, a rare genetic muscle-wasting disease caused by the absence of dystrophin, a protein necessary for muscle function. Currently, there are no approved disease-modifying therapiesfor DMD in the U.S. Eteplirsen is our lead therapeutic candidate for DMD. If we are successful in our development efforts, eteplirsen will address an unmetmedical need. We are in the process of conducting or starting several studies for product candidates designed to skip exons 45, 51 and 53 in the U.S. and inEurope. These are comprised of (i) studies to further evaluate eteplirsen that include an open label extension of our Phase IIb study, a confirmatory trial inambulatory patients, a study on participants with advanced stage DMD and a study with participants with early stage DMD, (ii) a dose-ranging study for ourproduct candidate designed to skip exon 45, (iii) a two-part randomized, double-blind, placebo-controlled, dose titration safety, tolerability andpharmacokinetics study (Part I) followed by an open label efficacy and safety study (Part II) with a product candidate designed to skip exon 53 and (iv) aplacebo-controlled confirmatory study with product candidates designed to skip exons 45 and 53 for which we have satisfactorily addressed FDA inquirieson preclinical data relating to the exon 53-skipping product candidate. On August 25, 2015, we announced the filing by the Food and Drug Administration(“FDA”) of our new drug application (“NDA”) for eteplirsen and it is under priority review with a current Prescription Drug User Fee Act (“PDUFA”) actiondate of May 26, 2016.We have also leveraged the capabilities of our RNA-targeted technology platforms to develop therapeutic candidates for the treatment of infectiousdiseases such as influenza, Marburg and Ebola under prior contracts with the Department of Defense (“DoD”), however, further development of these productcandidates would be conditioned, in part, on obtaining additional funding, collaborations or emergency use. Our discovery and research programs includecollaborations with various third parties and focus on developing therapeutics in rare, genetic, anti-bacterial, neuromuscular and central nervous systemdiseases amongst other diseases. We are exploring the application of our proprietary phosphorodiamidate morpholino oligomer (“PMO”) platformtechnology in various diseases.We believe we have developed proprietary state-of-the-art manufacturing and scale-up techniques that allow synthesis and purification of our productcandidates to support clinical development as well as potential commercialization. We have entered into certain manufacturing and supply arrangementswith third-party suppliers which will in part utilize these techniques to support production of certain of our product candidates and their components. Wecurrently do not have any of our own internal mid-to-large scale manufacturing capabilities to support our product candidates.The basis of our novel RNA-targeted therapeutics is the PMO. Our next generation PMO-based chemistries include PMO-X®, PMOplus® and PPMO.PMO and PMO-based compounds are highly resistant to degradation by enzymes, potentially enabling robust and sustained biological activity. In contrast toother RNA-targeted therapeutics, which are usually designed to down-regulate protein expression, our technologies are designed to selectively up-regulate ordown-regulate protein expression, and more importantly, create novel proteins. PMO and PMO-based compounds have demonstrated inhibition of messengerRNA (“mRNA”) translation and alteration of pre-mRNA splicing. PMO and PMO-based compounds have the potential to reduce off-target effects, such as theimmune stimulation often observed with ribose-based RNA technologies. We believe that our highly differentiated, novel, proprietary and innovative RNA-targeted PMO-based platforms may represent a significant improvement over other RNA-targeted technologies. In addition, PMO and PMO-basedcompounds are highly adaptable molecules: with minor structural modifications, they can potentially-40-be rapidly designed to target specific tissues, genetic sequences, or pathogens, and therefore, we believe they could potentially be applied to treat a broadspectrum of diseases.We have not generated any revenue from product sales to date and there can be no assurance that revenue from product sales will be achieved. Even ifwe do achieve revenue from product sales, we are likely to continue to incur operating losses in the near term.As of December 31, 2015, we had approximately $204.0 million of cash, cash equivalents and investments, consisting of $80.3 million of cash andcash equivalents, $112.2 million of short-term investments and $11.5 million of restricted cash and investments. We believe that our balance of cash, cashequivalents and investments is sufficient to fund our current operational plan for at least the next twelve months. As of December 31, 2014, we had completedall development activities under the agreements with the DoD. We are currently exploring possibilities for funding, collaboration and other avenues tosupport further development of these Ebola, Marburg and influenza product candidates. Without funding from the U.S. government, we would likely curtailcertain infectious disease research and development efforts, though we may pursue additional cash resources through public or private financings, seekadditional government contracts and establish collaborations with or license our technology to other companies.The likelihood of our long-term success must be considered in light of the expenses, difficulties and delays frequently encountered in thedevelopment and commercialization of new pharmaceutical products, competitive factors in the marketplace, the risks associated with government sponsoredprograms and the complex regulatory environment in which we operate. There can be no assurance that we will ever achieve significant revenue or profitableoperations.Summary and Timeline of Eteplirsen Data DisclosureIn October 2010, we announced results from a clinical trial of eteplirsen (“AVI Study 28”). Data from this study were published in The Lancet in July2011. AVI Study 28 was a Phase Ib/IIa open label, dose-ranging, clinical trial assessing the safety, tolerability, pharmacokinetics and exploratory efficacy ofeteplirsen in ambulatory individuals with DMD. Participants in AVI Study 28 were between the ages of five and 15 with errors in the gene coding fordystrophin, which were amenable to treatment by skipping exon 51. Participants were dosed once per week for 12 weeks. A total of 19 participants wereenrolled and these individuals were assigned to one of six dose cohorts of 0.5, 1.0, 2.0, 4.0, 10.0 or 20.0 mg/kg. Of the 19 participants enrolled, 18 received atleast ten of the 12 doses planned in this trial. After completion of dosing, participants were followed for an additional 14 weeks. Muscle biopsies were takenbefore treatment and 17 participants had a second biopsy at week 14, two weeks after administration of the final dose. The primary objective of the trial wasto assess the safety of eteplirsen at these doses over the 26-week duration of the trial. Secondary trial objectives included assessment of plasmapharmacokinetics, urinary elimination and exploratory endpoints evaluating biological activity and clinical performance. This trial was conducted byinvestigators in the United Kingdom at the University College London Institute of Child Health / Great Ormond Street Hospital in London and at the RoyalVictoria Infirmary in Newcastle-Upon-Tyne. In AVI Study 28, (i) eteplirsen induced exon 51 skipping in all cohorts and new dystrophin protein expression incohort 3; (ii) eteplirsen was well tolerated in all participants with no drug-related serious adverse events or severe adverse events observed, except that oneparticipant exhibited deteriorating cardiac function, which was considered probably disease related; (iii) adverse events were mostly mild or moderate inintensity, not dose-related, and none were considered probably or definitely related to eteplirsen; and (iv) there was no detectable immune response to newlymade dystrophin.Based on the AVI Study 28 results, we initiated a Phase IIb trial for eteplirsen in August 2011, AVI 4658-US-201 (“Study 201”), at NationwideChildren’s Hospital in Columbus, Ohio and we announced the results from this study in April 2012. This was a randomized, double-blind, placebo-controlledstudy to assess the efficacy, safety, tolerability and pharmacokinetics of eteplirsen administered intravenously in two different doses over 24 weeks for thetreatment of ambulant boys with DMD. Exploratory clinical measures of ambulation, muscle function and strength were also captured and evaluated duringthe course of the trial. Study 201 included 12 participants and muscle biopsies of all participants were performed prior to initiation of treatment. The12 participants with a genotypically-confirmed appropriate genetic mutation were randomized into one of three treatment groups with four participants ineach group. The first treatment group received a weekly intravenous administration of eteplirsen at a dose of 50.0 mg/kg. The second treatment groupreceived a weekly intravenous administration of eteplirsen at a dose of 30.0 mg/kg. The third and final treatment group received a weekly administration ofplacebo. Participants receiving the 50.0 mg/kg dose received a second biopsy at 12 weeks after initiation of treatment, and participants receiving the 30.0mg/kg dose received a second biopsy at 24 weeks after initiation of treatment. The results from Study 201 determined that treatment with eteplirsen met theprimary efficacy endpoint in the study. Eteplirsen administered once weekly at 30mg/kg over 24 weeks resulted in a statistically significant (p < 0.002)increase in the measurement taken of novel dystrophin (22.5% dystrophin-positive fibers as a percentage of normal) compared to no increase in the placebogroup. In the study, a shorter duration of eteplirsen treatment, 12 weeks, did not show a significant increase in the measurement taken of novel dystrophin(0.79% dystrophin-positive fibers as a percentage of normal; p-value NS), despite administration of the drug at a higher dose (50mg/kg once weekly). Nosignificant improvements in clinical outcomes in the treated groups were observed compared to placebo.-41-All participants in Study 201 were enrolled in an open-label extension study 4658-US-202 (“Study 202”), following the completion of Study 201 andall participants, including those from the placebo group in Study 201, are receiving either 30.0 mg/kg or 50.0 mg/kg for the duration of Study 202. Thepurpose of Study 202 is to evaluate the ongoing safety, efficacy and tolerability of eteplirsen. The primary efficacy endpoint was the change from baseline atweek 48 in the percentage of dystrophin-positive fibers in muscle biopsy tissue as measured by immunohistochemistry. The primary clinical outcomemeasure was the change from baseline to week 48 on the six-minute walk test (“6MWT”). Study 202 is now in a long-term extension phase in which patientswere followed for safety and clinical outcomes approximately every 12 weeks through week 108 (which includes the original 28 weeks of Study 201).In July 2012, we announced interim results from Study 202 which indicated that treatment with eteplirsen over 36 weeks achieved a significantclinical benefit on the primary clinical outcome measure, the 6MWT, over a placebo/delayed treatment cohort. Eteplirsen administered once weekly at50mg/kg over 36 weeks resulted in a 69.4 meter benefit compared to patients who received placebo for 24 weeks followed by 12 weeks of treatment witheteplirsen. In the predefined prospective analysis of the study’s intent-to-treat (“ITT”) population on the primary clinical outcome measure, the change in6MWT distance from baseline, eteplirsen-treated patients who received 50mg/kg of the drug weekly demonstrated a decline of 8.7 meters in distance walkedfrom baseline (mean=396.0 meters), while patients who received placebo/delayed-eteplirsen treatment for 36 weeks showed a decline of 78.0 meters frombaseline (mean=394.5 meters), for a statistically significant treatment benefit of 69.4 meters over 36 weeks (p < 0.019). There was no statistically significantdifference in the 6MWT between the cohort of patients who received 30mg/kg weekly of eteplirsen and the placebo/delayed treatment cohort. The safetyprofile of eteplirsen was evaluated across all subjects through the 36 weeks eteplirsen was administered and there were no treatment-related adverse events,no serious adverse events and no discontinuations. Furthermore, no treatment-related changes were detected on any safety laboratory parameters, includingseveral biomarkers for renal function.In October 2012, we announced 48-week results from Study 202 which indicated that treatment with eteplirsen met the predefined primary efficacyendpoint, increased in the measurement taken of novel dystrophin, and achieved a significant clinical benefit on the predefined primary clinical outcomemeasure, the 6MWT, over the placebo/delayed treatment cohort. Eteplirsen administered once weekly at either 30 mg/kg or 50 mg/kg for 48 weeks (n=8)resulted in a statistically significant increase (p<0.001) in the measurement taken of dystrophin-positive fibers to 47.0% of normal. The placebo/delayedtreatment cohort, which had received 24 weeks of eteplirsen at either 30 mg/kg or 50 mg/kg following 24 weeks of placebo (n=4), also showed a statisticallysignificant increase in the measurement taken of dystrophin-positive fibers to 38.3% of normal (p<0.009).In the predefined analysis of the study’s ITT population on the primary clinical outcome measure, the change in 6MWT distance from baseline atweek 48, eteplirsen-treated patients who received 50 mg/kg of the drug weekly (n=4) demonstrated an increase of 21.0 meters in distance walked frombaseline (mean=396.0 meters), while patients who received placebo/delayed-eteplirsen treatment (n=4) showed a decline of 68.4 meters from baseline(mean=394.5 meters), for a statistically significant treatment benefit of 89.4 meters over 48 weeks (p=0.016, using analysis of covariance for ranked datausing mixed model repeated measures). There was no statistically significant difference between the cohort of patients who received 30 mg/kg weekly ofeteplirsen and the placebo/delayed treatment cohort. The safety profile of eteplirsen was evaluated across all subjects through 48 weeks and there were notreatment-related adverse events, no serious adverse events, and no discontinuations. Furthermore, no clinically significant treatment-related changes weredetected on any safety laboratory parameters, including several biomarkers for renal function.In December 2012, we announced updated data from Study 202 which showed that patients treated with eteplirsen and evaluable on ambulatorymeasures in a modified intent-to-treat population (“mITT population”) for 62 weeks maintained a statistically significant clinical benefit on the primaryclinical outcome measure, the 6MWT, compared to patients who received placebo for 24 weeks followed by 38 weeks of eteplirsen treatment. In the mITTpopulation, which includes evaluable patients from both the 30mg/kg and 50mg/kg dose cohorts, patients treated with eteplirsen for 62 weeks demonstrateda statistically significant benefit (p < 0.007) of 62 meters over the placebo/delayed-treatment cohort using a mixed-model repeated measure statistical test.The mITT population utilized for the 62 week analysis consisted of 10 of the enrolled 12 patients (four eteplirsen-treated patients receiving 50 mg/kgweekly, 2 eteplirsen-treated patients receiving 30 mg/kg weekly, and 4 placebo/delayed-treatment patients), and excluded two patients who showed signs ofrapid disease progression and lost ambulation by week 24. The eteplirsen treatment cohort (n=6) continued to show disease stabilization with less than a 5%decline in walking distance on the 6MWT from baseline. The placebo/delayed-treatment cohort (n=4) also demonstrated stability in walking distance fromweek 36 through week 62 with a less than 10 meter change over this timeframe, the period in which dystrophin was likely produced, with confirmation ofsignificant dystrophin levels at week 48 through analysis of muscle biopsies in these patients.The safety profile of eteplirsen was evaluated across all patients through week 62 and there were no clinically significant treatment-related adverseevents, no serious adverse events, and no discontinuations. One patient had a laboratory treatment-related adverse event, a transient elevation of urine proteinon a urine dipstick test, however this elevation was not observed on a 24-hour urine protein measurement and resulted in no clinical symptoms orinterruption of treatment. This patient did not show elevations of the specific renal markers of cystatin C or KIM-1. Across both the treatment andplacebo/delayed treatment cohorts there is evidence of continued stabilization on pulmonary function tests, echocardiogram, muscle strength and clinicallaboratory tests over the 62 weeks.-42-Results from the mITT population, which combines the evaluable eteplirsen-treated patients across the 30mg/kg and 50mg/kg cohorts, have beenpreviously reported and will be used as the primary assessment of ambulatory clinical measures for the remainder of Study 202. Given there was nosignificant difference between the 30 mg/kg and 50 mg/kg arms on the production of dystrophin through 48 weeks based on the measurements taken, webelieve this mITT population is the most appropriate to assess dystrophin production and its potential predictive benefits on ambulatory clinical outcomes,such as the 6MWT.In April 2013, we announced that, after 74 weeks, patients in the 30 mg/kg and 50 mg/kg dose cohorts in the mITT population (n=6) showed astatistically significant treatment benefit of 65.2 meters (p <0.004) when compared to the placebo/delayed-treatment cohort (n=4). The eteplirsen-treatedpatients in the mITT population demonstrated less than 13.4 meters, or 5 percent decline from baseline in walking ability. After experiencing a substantialdecline earlier in the study, the placebo/delayed-treatment cohort also demonstrated stabilization in walking ability from week 36 through 74, the period inwhich meaningful levels of dystrophin were likely produced, with a less than 10 meter decline over this timeframe. Through 74 weeks, eteplirsen was welltolerated and there were no clinically significant treatment-related adverse events, serious adverse events, hospitalizations or discontinuations. As previouslyreported at 62 weeks, one patient had a transient elevation of urine protein on a laboratory urine dipstick test, which resolved and resulted in no clinicalsymptoms. The patient continued treatment without interruption and remained free of proteinuria through week 74. Across both the eteplirsen-treated andplacebo/delayed-treatment cohorts, there was evidence of continued stabilization on clinical laboratory tests, echocardiogram, pulmonary function tests andmuscle strength through 74 weeks of participating in Study 202.In June 2013, we announced that after 84 weeks, patients in the 30 mg/kg and 50 mg/kg dose cohorts in the mITT population (n=6) showed astatistically significant treatment benefit of 46.4 meters (p<0.045) when compared to the placebo/delayed-treatment cohort (n=4). The eteplirsen-treatedpatients in the mITT population demonstrated less than a 6 percent decline (20.5 meters) from baseline in walking ability. The placebo/delayed-treatmentcohort also demonstrated stabilization in walking ability from Week 36 through 84, the period from which meaningful levels of dystrophin were likelyproduced, with an increase of 3.3 meters over this timeframe. These analyses were based on the maximum 6MWT score when the test was performed on twoconsecutive days. Through 84 weeks, eteplirsen was well tolerated and there were no clinically significant treatment-related adverse events, no seriousadverse events, hospitalizations or discontinuations. One boy in the placebo/delayed-treatment cohort was not able to perform the 6MWT at the Week 84clinic visit due to a physical injury unrelated to treatment, and therefore had no 6MWT data captured at the Week 84 time point. The boy has recovered fromthe injury, continues to be ambulatory and is expected to be evaluated on the 6MWT at future clinic visits. Across all patients in the eteplirsen andplacebo/delayed-treatment cohorts, there was evidence of continued stabilization on clinical laboratory tests, echocardiograms, pulmonary function tests andmeasures of muscle strength through 84 weeks of participating in Study 202.In September 2013, we announced that after 96 weeks, patients in the 30 mg/kg and 50 mg/kg eteplirsen cohorts in the mITT population (n=6)experienced less than 17.5 meters, or 5% decline from baseline in walking ability. A statistically significant treatment benefit of 70.8 meters (p <0.001) wasobserved for the mITT population compared with the placebo/delayed-treatment cohort (n=4). The placebo/delayed-treatment cohort also demonstratedstabilization in walking ability from Week 36 through 96, the period from which meaningful levels of dystrophin were likely produced, with a decline of18.5 meters over this timeframe. These analyses were based on the maximum 6MWT score when the test was performed on two consecutive days. Aspreviously reported, a boy in the placebo/delayed-treatment cohort was not able to perform the 6MWT at the Week 84 clinic visit due to a broken ankleassessed by the investigator as a treatment-unrelated adverse event. Although this boy received rehabilitation and was able to perform the 6MWT, hiswalking ability at the time of the test had not returned to the level observed prior to the injury, and this lower 6MWT distance contributed to the overalldecline in the placebo/delayed-treatment cohort. The decline in walking distance observed in this cohort from Week 36 improves from a decline of 18.5meters to a decline of 4.7 meters when this patient’s 96-week test score is excluded from the analysis. Through 96 weeks, eteplirsen was well tolerated andthere were no reported clinically significant treatment-related adverse events, no treatment-related serious adverse events, hospitalizations ordiscontinuations. Across patients in the eteplirsen and placebo/delayed-treatment cohorts, there is evidence of continued stabilization on clinical laboratorytests, echocardiograms, pulmonary function tests and measures of muscle strength through 84 weeks of participating in Study 202.In January 2014, we announced that at 120 weeks, patients in the 30 mg/kg and 50 mg/kg eteplirsen cohorts who were able to perform the 6MWT(mITT population; n=6) experienced a decline of 13.9 meters, or less than 5 percent, from baseline in walking ability. A statistically significant treatmentbenefit of 64.9 meters (p <0.006) was observed for the mITT population compared with the placebo/delayed-treatment cohort (n=4). The placebo/delayed-treatment cohort also demonstrated stabilization in walking ability for more than 1.5 years, from Week 36 through 120, the period from which meaningfullevels of dystrophin were likely produced, with a decline of 9.5 meters over this timeframe. These analyses were based on the maximum 6MWT score whenthe test was performed on two consecutive days. In addition, in February 2014, we announced that results through more than two years of treatment showedstable pulmonary function in the ITT study population (n=12). Through 120 weeks, eteplirsen was well tolerated and there were no reported clinicallysignificant treatment-related adverse events and no treatment-related serious adverse events. In addition, there were no treatment-related hospitalizations ordiscontinuations.-43-In July 2014, we announced that at 144 weeks, patients in the 30 mg/kg and 50 mg/kg eteplirsen cohorts who were able to perform the 6MWT (mITTpopulation; n=6) experienced a decline of 33.2 meters, or about 8.5 percent, from baseline in walking ability. A statistically significant treatment benefit of75.1 meters (p <0.004) was observed for the mITT population compared with the placebo/delayed-treatment cohort (n=4), which initiated treatment at Week25 following 24 weeks of placebo. After experiencing a substantial decline of 68.4 meters from baseline to Week 36, the placebo/delayed-treatment cohortdemonstrated a decline of 39.0 meters in walking ability from Week 36 through Week 144, the period from which meaningful levels of dystrophin werelikely produced. These analyses were based on the maximum 6MWT score when the test was performed on two consecutive days. Respiratory musclefunction from baseline through Week 144 in the ITT population (n=12), as measured by maximum inspiratory and expiratory pressure (MIP and MEP),showed a 14.7 percent mean increase in MIP and a 12.8 percent mean increase in MEP. Analyses of MIP percent predicted (MIP adjusted for weight) and MEPpercent predicted (MEP adjusted for age) demonstrated a mean change from 91.7 percent at baseline to 93.9 percent at Week 144 in MIP percent predicted,and a mean change from 79.3 percent at baseline to 75.7 percent at Week 144 in MEP percent predicted. In addition, there was a mean increase in forced vitalcapacity (“FVC”), a measure of lung volume, of 11.0 percent. FVC percent predicted (FVC adjusted for age and height) was maintained above a mean of 90percent at Week 144, with 101.3 percent at baseline and 90.9 percent at Week 144. Through 144 weeks, eteplirsen was well tolerated and there were noreported clinically significant treatment-related adverse events and no treatment-related serious adverse events. In addition, there were no treatment-relatedhospitalizations or discontinuations.In January 2015, we announced that at Week 168, the six patients in the mITT population in the 30 and 50 mg/kg eteplirsen cohorts who were able toperform the 6MWT experienced a decline of 76.7 meters, or about 19.5 percent, from baseline in walking ability. A statistically significant treatment benefitof 65.4 meters (p <0.017) was observed compared with the placebo/delayed-treatment cohort (n=4), which initiated treatment at Week 25 following 24 weeksof placebo. This cohort, after experiencing a substantial decline of 68.4 meters from baseline to Week 36, demonstrated a decline of 73 meters in walkingability from Week 36 through Week 168, the period from which meaningful levels of dystrophin were likely produced. These analyses were based on themaximum 6MWT score when the test was performed on two consecutive days. Respiratory muscle function from baseline through Week 168 in the Intent-to-Treat population (n=12), as measured by maximum inspiratory and expiratory pressure (MIP and MEP), continued to show a 11.1 percent mean increase inMIP and a 14.7 percent mean increase in MEP. Analyses of MIP percent predicted (MIP adjusted for weight) and MEP percent predicted (MEP adjusted forage) demonstrated a mean change from 91.7 percent at baseline to 89.5 percent at Week 168 in MIP percent predicted, and a mean change from 79.3 percentat baseline to 74.3 percent at Week 168 in MEP percent predicted. In addition, there was a mean increase in FVC, a measure of lung volume, of 11.6 percent.FVC percent predicted (FVC adjusted for age and height) was maintained above a mean of 90 percent at Week 168, with 101.3 percent at Baseline and 91.9percent at Week 168. Through 168 weeks, eteplirsen was well tolerated and there were no reported clinically significant treatment-related adverse events andno treatment-related serious adverse events. In addition, there were no treatment-related hospitalizations or discontinuations.In October 2015, we announced additional clinical efficacy and safety data that demonstrated that (i) eteplirsen provided a statistically significantadvantage of 151 meters in the ability of study participants to walk (as measured by the 6MWT) at three years, compared with external controls, (ii) the fourthbiopsy data confirmed the mechanism of action of eteplirsen, demonstrating exon skipping in all patients and dystrophin production in nearly all patientsand (iii) at three years, the safety data remained consistent with prior results. In January 2016, the FDA made public our eteplirsen Briefing DocumentAddendum (the “January 2016 Addendum”) which disclosed that at four years, 10 out of 12 patients on eteplirsen remained ambulatory while 10 out of 13untreated patients in the external control had lost ambulation (one patient in the external control was still ambulatory at year 4, while 2 patients in theexternal control were missing data at 4 years), a statistically significant difference. In addition, the January 2016 Addendum disclosed a statisticallysignificant advantage of 162 meters in the ability of study participants to walk (as measured by the 6MWT) at four years. Key Financial MetricsRevenueGovernment Research Contract and Grant Revenue. In the periods presented in this report, substantially all of our revenues were derived from researchand development contracts with and grants from the U.S. government. We recognize revenue from U.S. government research contracts and grants during theperiod in which the related expenses are incurred and present such revenues and related expenses on a gross basis in the consolidated financial statements.Our government contracts are subject to government audits, which may result in catch-up adjustments. As of December 31, 2014, we had completed alldevelopment activities of our contracts with the U.S. government. The majority of the revenue under our U.S. government contracts was recognized as ofDecember 31, 2015 and only revenue for contract finalization, if any, is expected in the future.If a technology, right, product or service is separate and independent of our performance under other elements of an arrangement, we defer recognitionof non-refundable up-front fees if we have continuing performance obligations when the technology, right, product or service conveyed in conjunction withthe non-refundable fee has no utility to the licensee. In addition, if we have continuing involvement through research and development services that arerequired because of our know-how or because the-44-services can only be performed by us, such up-front fees are deferred and recognized over the period of continuing involvement. As of December 31, 2015, wehad deferred revenue of $3.3 million, which represents up-front fees we may recognize as revenue upon settlement of certain obligations.ExpensesResearch and Development. Research and development expenses consist of costs associated with research activities as well as costs associated withour product development efforts, conducting preclinical studies, clinical trials and manufacturing activities.Direct research and development expenses associated with our programs include clinical trial site costs, clinical manufacturing costs, costs incurred forconsultants and other external services, such as data management and statistical analysis support, and materials and supplies used in support of clinicalprograms. Indirect costs of our clinical programs include salaries, stock-based compensation and allocation of our facility costs.Future research and development expenses may increase as our internal projects, such as those for our DMD product candidates, enter or proceedthrough later stage clinical development. We are currently conducting various clinical trials for eteplirsen, including a confirmatory trial in the U.S. Wecompleted Part I and have started conducting Part II of a Phase I/IIa clinical trial for an exon 53-skipping product candidate in the E.U. We have also initiateda dose-ranging study for our exon 45-skipping product candidate in the U.S. We are also planning to initiate a placebo-controlled confirmatory study withproduct candidates designed to skip exons 45 and 53 in the U.S. and E.U. The remainder of our research and development programs are in various stages ofresearch and pre-clinical development. However, our research and development efforts may not result in any approved products. Product candidates thatappear promising at early stages of development may not reach the market for a variety of reasons. Similarly, any of our product candidates may be found tobe unsafe or ineffective during clinical trials, may have clinical trials that take longer to complete than anticipated, may fail to receive necessary regulatoryapprovals, or may prove impracticable to manufacture in commercial quantities at reasonable cost and with acceptable quality.As a result of these uncertainties and the other risks inherent in the drug development process, we cannot determine the duration or completion costsof current or future clinical stages of any of our product candidates. Similarly, we cannot determine when, if, or to what extent we may generate revenue fromthe commercialization of any product candidate. The time frame for development of any product candidate, associated development costs and the probabilityof regulatory and commercial success vary widely.General and Administrative. General and administrative expenses consist of salaries, benefits, stock-based compensation and related costs forpersonnel in our executive, finance, legal, information technology, business development, human resources, commercial and other general and administrativefunctions. Other general and administrative expenses include an allocation of our facility costs and professional fees for legal, consulting and accountingservices.Interest Income and Other, Net. Interest income and other, net, primarily consists of interest income on our cash, cash equivalents and investments,interest expense and rental income and loss. Our cash equivalents and investments consist of commercial paper, government and government agency debtsecurities, money market investments and certificates of deposit. Interest expense includes interest accrued on our promissory note related to the Andover,Massachusetts facility, our senior secured term loan and our mortgage loan related to our Corvallis, Oregon property, a substantial portion of which has beenleased to a third party since November 2011. Rental income and loss is from leasing excess space in some of our facilities.Loss on Change in Warrant Valuation. Warrants issued in connection with our January and August 2009 financings were classified as liabilities asopposed to equity due to their settlement terms. These warrants were non-cash liabilities and we were not required to expend any cash to settle theseliabilities. The fair value of these warrants was recorded on our consolidated balance sheets at the date of issuance. The warrants were marked to market ateach financial reporting period, with changes in the fair value recorded as “Gain (loss) on change in warrant valuation” in our consolidated statements ofoperations and comprehensive loss. The fair value of the warrants was determined using the Black-Scholes-Merton option-pricing model, which required theuse of significant judgment and estimates related to the inputs used in the model. All warrants issued in January and August 2009 were exercised or expiredduring 2014.Critical Accounting Policies and EstimatesThe discussion and analysis of our financial condition and results of operations are based upon our consolidated financial statements includedelsewhere in this Annual Report on Form 10-K. The preparation of our consolidated financial statements in accordance with accounting principles generallyaccepted in the United States (“U.S. GAAP”) requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues andexpenses and related disclosure of contingent assets and liabilities for the periods presented. Some of these judgments can be subjective and complex, and,consequently, actual results may differ from these estimates. For any given individual estimate or assumption we make, there may also be other estimates or-45-assumptions that are reasonable. We believe that the estimates and judgments upon which we rely are reasonable based upon historical experience andinformation available to us at the time that we make these estimates and judgments. To the extent there are material differences between these estimates andactual results, our consolidated financial statements will be affected. Although we believe that our judgments and estimates are appropriate, actual resultsmay differ from these estimates.The policies that we believe are the most critical to aid the understanding of our financial results include: ·revenue recognition; ·research and development expense; ·stock-based compensation; and ·income tax.Revenue RecognitionWe have historically generated revenue from our U.S. government research contracts and other grants. During the periods presented, substantially allof our revenue was generated from U.S. government research contracts and grants, which are generally cost plus contracts providing for reimbursed costswhich include overhead and general and administrative costs and a target fee. We recognize revenue from U.S. government research contracts during theperiod in which the related expenses are incurred and present such revenues and related expenses on a gross basis in the consolidated financial statements.Our government contracts are subject to government audits, which may result in catch-up adjustments.Research and Development ExpensesAll research and development expenses, including amounts funded through research and development collaborations, are expensed as incurred.Research and development expenses are comprised of costs incurred in performing research and development activities, including salary and benefits, stock-based compensation expense, laboratory supplies and other direct expenses, contractual services including clinical trial and pharmaceutical developmentcosts, expenses associated with the supply investment in our drug candidates and infrastructure costs including facilities costs and depreciation.We defer and capitalize non-refundable advance payments for goods or services that will be used or rendered for future research and developmentactivities pursuant to executory contractual arrangements and recognized as an expense as the related goods are delivered or the related services areperformed. If we do not expect the goods to be delivered or services to be rendered, the advance payment capitalized will be charged as an expense.When third-party service providers’ billing terms do not coincide with our period-end, we are required to make estimates of our obligations to thosethird parties, including clinical trial and pharmaceutical development costs, contractual services costs and costs for supply of our drug candidates, incurred ina given accounting period and record accruals at the end of the period. We base our estimates on our knowledge of the research and development programs,services performed for the period and past history, where applicable.Stock Compensation ExpenseWe use the fair value method to determine stock-based compensation expense. To determine the fair value of stock-based awards on the date of grant,we use the Black-Scholes-Merton option-pricing model. The Black-Scholes-Merton option-pricing model requires the use of subjective and complexassumptions which include the award’s expected term and the price volatility of the underlying stock. We recognize the fair value of the portion of theawards expected to vest as expense over the requisite vesting periods on a straight-line basis for the entire award. Stock awards granted to employees vestover a four-year period and have a ten-year term. Forfeitures are estimated at the time of grant and revised, if necessary, in subsequent periods if actualforfeitures differ from those estimates.The assumptions used in calculating the fair value of stock-based compensation expense represent management’s best estimates, but these estimatesinvolve inherent uncertainties and the application of management judgment. As a result, if factors change and we use different assumptions, our stock-basedcompensation expense could be materially different in the future. Please read Note 11, Stock-Based Compensation to the consolidated financial statementsincluded elsewhere in this Annual Report on Form 10-K for a further discussion of stock-based compensation.-46-Income TaxWe follow the asset and liability method of accounting for income taxes. Deferred tax assets and liabilities are recognized for the future taxconsequences attributable to differences between the consolidated financial statement carrying amounts of existing assets and liabilities and their respectivetax bases and operating loss and tax credit carryforwards. It is our intention to reinvest the earnings of our non-U.S. subsidiaries in those operations and not torepatriate the earnings to the U.S. Accordingly, we do not provide for deferred taxes on the excess of the financial reporting over the tax basis in itsinvestments in foreign subsidiaries as they are considered permanent in duration. To date, we have not had any earnings in our non-U.S. subsidiaries.Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in the years in which those temporarydifferences are expected to be recovered and settled. A valuation allowance is recorded to reduce the net deferred tax asset to zero because it is more likelythan not that the net deferred tax asset will not be realized. We recognize the effect of income tax positions only if those positions are more likely than not tobe sustained upon an examination. Please read Note 13, Income Taxes to the consolidated financial statements included elsewhere in this Annual Report onForm 10-K for a further discussion of income tax.Results of Operations for the years ended December 31, 2015, 2014 and 2013The following table sets forth selected consolidated statements of operations data for each of the periods indicated: For the Year Ended December 31 2015 2014 Change Change (in thousands, except pershare amounts) $ % Revenue from research contracts and other grants$1,253 $9,757 $(8,504) (87)%Operating expenses: Research and development 146,394 94,231 52,163 55%General and administrative 75,043 49,315 25,728 52%Total operating expenses 221,437 143,546 77,891 54%Operating loss (220,184) (133,789) (86,395) 65%Other income (loss): Interest income and other, net 154 779 (625) (80)%Loss on change in warrant valuation — (2,779) 2,779 (100)%Net loss$(220,030) $(135,789) $(84,241) 62% Net loss per share — basic and diluted$(5.20) $(3.39) $(1.81) 53% For the Year Ended December 31 2014 2013 Change Change (in thousands, except pershare amounts) $ % Revenue from research contracts and other grants$9,757 $14,219 $(4,462) (31)%Operating expenses: Research and development 94,231 72,909 21,322 29%General and administrative 49,315 31,594 17,721 56%Total operating expenses 143,546 104,503 39,043 37%Operating loss (133,789) (90,284) (43,505) 48%Other income (loss): Interest income and other, net 779 326 453 139%Loss on change in warrant valuation (2,779) (22,027) 19,248 (87)%Net loss$(135,789) $(111,985) $(23,804) 21% Net loss per share — basic and diluted$(3.39) $(3.31) $(0.08) 2% -47-RevenueRevenue for 2015 decreased by $8.5 million, or 87%, compared to 2014. For the year ended December 31, 2015, we recognized $1.3 million fromcontract finalization of the Ebola portion of the July 2010 DoD contract for the advanced development of our hemorrhagic virus therapeutic candidatesagainst the Ebola and Marburg viruses (the “July 2010 Agreement”), which is expected to be collected from the U.S. government in 2016. For the year endedDecember 31, 2014, we recognized $9.8 million under various U.S. government contracts. The majority of the revenue under our U.S. government contractswas recognized as of December 31, 2015 and only revenue for contract finalization, if any, is expected in the future.Revenue for 2014 decreased by $4.5 million, or 31%, compared to 2013. The decrease was due to a decrease of $2.8 million in the August 2012 DoDcontract to evaluate the feasibility of an intramuscular route of administration using our candidate for treatment of the Marburg virus, which was concludedin the third quarter of 2013, $2.2 million in revenue associated with the Marburg portion of the July 2010 Agreement, which expired in July 2014, and$0.4 million in the June 2010 DoD contract to advance the development of AVI-7100 as a medical countermeasure against the pandemic H1N1 influenzavirus. These decreases were partially offset by an increase of $0.9 million in our collaboration agreement with Carolinas Medical Center and $0.2 million inour agreement for a collaborative research project partially funded by the E.U. Health Innovation.Research and Development ExpensesOur research and development programs span various disease targets. The lengthy process of securing FDA approvals for new drugs requiressubstantial resources. Accordingly, we cannot currently estimate, with any degree of certainty, the amount of time or money that we will be required toexpend in the future on our product candidates prior to their regulatory approval, if such approval is ever granted.Research and development expenses represent a substantial percentage of our total operating expenses, which primarily consist of costs associatedwith research activities as well as costs associated with our product development efforts, conducting preclinical studies, and clinical trials and manufacturingactivities. We do not maintain or evaluate, and therefore do not allocate, internal research and development costs on a project-by-project basis. As a result, asignificant portion of our research and development expenses are not tracked on a project-by-project basis, as the costs may benefit multiple projects.The following table summarizes our research and development expenses by project for each of the periods indicated: For the Year Ended December 31 2015 2014 Change Change (in thousands) $ % Eteplirsen (exon 51)$72,147 $29,395 $42,752 145%Exon 45 6,649 4,343 2,306 53%Exon 53 5,583 8,013 (2,430) (30)%Other projects 2,178 4,196 (2,018) (48)%Internal research and development expenses 59,837 48,284 11,553 24%Total research and development expenses$146,394 $94,231 $52,163 55% For the Year Ended December 31 2014 2013 Change Change (in thousands) $ % Eteplirsen (exon 51)$29,395 $36,461 $(7,066) (19)%Exon 45 4,343 32 4,311 13,472%Exon 53 8,013 2,631 5,382 205%Other projects 4,196 8,191 (3,995) (49)%Internal research and development expenses 48,284 25,594 22,690 89%Total research and development expenses$94,231 $72,909 $21,322 29% -48-The following table summarizes our research and development expenses by category for each of the periods indicated: For the Year Ended December 31 2015 2014 Change Change (in thousands) $ % Clinical and manufacturing expenses$80,977 $39,505 $41,472 105%Compensation and other personnel expenses 25,746 20,234 5,512 27%Stock-based compensation 10,403 8,269 2,134 26%Facility-related expenses 9,919 7,792 2,127 27%Professional services 8,329 7,689 640 8%Preclinical expenses 3,948 2,758 1,190 43%Research and other 7,072 7,984 (912) (11)%Total research and development expenses$146,394 $94,231 $52,163 55% For the Year Ended December 31 2014 2013 Change Change (in thousands) $ % Clinical and manufacturing expenses$39,505 $36,876 $2,629 7%Compensation and other personnel expenses 20,234 13,653 6,581 48%Stock-based compensation 8,269 3,888 4,381 113%Facility-related expenses 7,792 4,859 2,933 60%Professional services 7,689 2,425 5,264 217%Preclinical expenses 2,758 4,752 (1,994) (42)%Research and other 7,984 6,456 1,528 24%Total research and development expenses$94,231 $72,909 $21,322 29% Research and development expenses for 2015 increased by $52.2 million, or 55%, compared to 2014. The increase was primarily due to increases of$41.5 million in clinical and manufacturing expenses, driven by increased enrollment in our ongoing clinical trials and timing of manufacturing activities(including raw material purchases) as well as expense incurred in connection with an amendment to a supply agreement, $5.5 million in compensation andother personnel expenses primarily driven by increases in headcount, $2.1 million in stock-based compensation and $2.1 million from facility-relatedexpenses primarily driven by corporate growth.Research and development expenses for 2014 increased by $21.3 million, or 29%, compared to 2013. The increase was primarily driven by increasesof $6.6 million in compensation and other personnel expenses, $5.3 million in professional services, $4.4 million in stock-based compensation expense, $2.9million in facility-related expenses and $2.6 million in clinical and manufacturing expenses.-49-General and Administrative ExpensesThe following table summarizes our general and administrative expenses by category for each of the periods indicated: For the Year Ended December 31 2015 2014 Change Change (in thousands) $ % Professional services$25,884 $16,363 $9,521 58%Compensation and other personnel expenses 17,513 12,454 5,059 41%Stock-based compensation 12,329 11,921 408 3%Former CEO severance expense 9,182 — 9,182 NA Facility-related expenses 2,838 2,616 222 8%Other 7,297 5,961 1,336 22%Total general and administrative expenses$75,043 $49,315 $25,728 52% For the Year Ended December 31 2014 2013 Change Change (in thousands) $ % Professional services$16,363 $7,934 $8,429 106%Compensation and other personnel expenses 12,454 10,933 1,521 14%Stock-based compensation 11,921 7,190 4,731 66%Facility-related expenses 2,616 854 1,762 206%Other 5,961 4,683 1,278 27%Total general and administrative expenses$49,315 $31,594 $17,721 56% General and administrative expenses for 2015 increased by $25.7 million, or 52%, compared to 2014. The increase was primarily due to $9.5 millionin professional services driven by increased legal fees and preparation for the potential product launch for eteplirsen if market approval is obtained, $9.2million in severance expense, including stock-based compensation, as a result of the resignation of our former CEO, and $5.1 million in compensation andother personnel expenses primarily driven by increases in headcount. General and administrative expenses for 2014 increased by $17.7 million, or 56%, compared to 2013. The increase in general and administrativeexpenses is primarily due to increases of $8.4 million in professional services, $4.7 million in stock-based compensation expenses, facility-related expensesof $1.8 million and $1.5 million in compensation and other personnel expenses, primarily driven by increases in headcount.Interest Income and Other, NetInterest income and other, net for 2015 decreased by $0.6 million compared to 2014. The decrease was primarily driven by an increase in interestexpense incurred in connection with the $20.0 million senior secured term loan.Interest income and other, net for 2014 increased by $0.5 million compared to 2013. The increase was primarily driven by interest income from short-term investments.-50-Liquidity and Capital ResourcesThe following table summarizes our financial condition for each of the periods indicated: As ofDecember 31,2015 As ofDecember 31,2014 Change Change (in thousands) $ % Financial assets: Cash and cash equivalents $80,304 $73,551 $6,753 9%Short-term investments 112,187 136,793 (24,606) (18)%Restricted cash and investments 11,478 782 10,696 1368%Total cash, cash equivalents and investments $203,969 $211,126 $(7,157) (3)% Borrowings: Long-term debt $20,905 $1,574 $19,331 1228%Notes payable 2,493 4,754 (2,261) (48)%Total borrowings $23,398 $6,328 $17,070 270% Working capital Current assets $224,543 $247,796 $(23,253) (9)%Current liabilities 62,294 36,867 25,427 69%Total working capital $162,249 $210,929 $(48,680) (23)% For the year ended December 31, 2015, our principal sources of liquidity were from equity and debt financings. For the year ended December 31,2014, our principal source of liquidity was from an equity financing. Our principal uses of cash are research and development expenses, general andadministrative expenses, capital expenditures and other working capital requirements.Our future expenditures and capital requirements may be substantial and will depend on many factors, including but not limited to the following: ·the timing and costs associated with commercialization of eteplirsen should marketing approval ever be granted; ·the timing and costs of building out our manufacturing capabilities; ·the timing of advanced payments related to our future inventory commitments; ·the timing and costs associated with our clinical trials and preclinical studies; and ·the costs of filing, prosecuting, defending and enforcing patent claims and our other intellectual property rights.Our cash requirements are expected to continue to increase as we advance our research, development and commercialization programs and we expectto seek additional financing primarily from, but not limited to, the sale and issuance of equity, debt securities or the licensing or sale of our technology. Wecannot provide assurances that financing will be available when and as needed or that, if available, the financings will be on favorable or acceptable terms. Ifwe are unable to obtain additional financing when and if we require, this would have a material adverse effect on our business and results of operations. Tothe extent we issue additional equity securities, our existing stockholders could experience substantial dilution.-51-Cash FlowsThe following table summarizes our cash flow activity for each of the periods indicated: For the Year Ended December 31 2015 2014 Change Change (in thousands) $ % Cash provided by (used in) Operating activities $(149,465) $(128,539) $(20,926) 16%Investing activities 8,410 (159,030) 167,440 (105)%Financing activities 147,808 104,155 43,653 42%Increase (decrease) in cash and cash equivalents $6,753 $(183,414) $190,167 (104)% For the Year Ended December 31 2014 2013 Change Change (in thousands) $ % Cash provided by (used in) Operating activities $(128,539) $(64,695) $(63,844) 99%Investing activities (159,030) (11,672) (147,358) 1,262%Financing activities 104,155 145,671 (41,516) (28)%(Decrease) increase in cash and cash equivalents $(183,414) $69,304 $(252,718) (365)%Operating Activities.Cash used in operating activities for 2015 increased by $20.9 million compared to 2014. The increase was primarily due to an increase of $84.2million in net loss driven by increases in research and development and general and administrative expenses partially offset by a favorable change of $54.1million in operating assets and liabilities due to the timing of certain activities and an increase in non-cash adjustments of $9.2 million.Cash used in operating activities for 2014 increased by $63.8 million compared to 2013. The increase was primarily due to an increase of $23.8million in net loss driven by lower revenues from contracts with the U.S. government and increases in research and development and general andadministrative expenses, an unfavorable change of $34.4 million in operating assets and liabilities due to the timing of certain activities and a decrease innon-cash adjustments of $5.6 million.Investing Activities.Cash provided by investing activities was $8.4 million for 2015 while cash used in investing activities was $159.0 million for 2014. The change wasprimarily due to an increase of $51.0 million from the maturity of available-for-sale securities and decreases of $112.4 million from the purchase of available-for-sale securities and $22.0 million from the purchase of property and equipment partially offset by the purchase of restricted investments of $10.7 million.Additionally, for the year ended December 31, 2014, $7.3 million of restricted investments matured.Cash used in investing activities for 2014 increased by $147.4 million compared to 2013. The increase was primarily due to the purchase of available-for-sale securities of $274.4 million and an increase of $23.1 million in the purchase of property and equipment partially due to the acquisition of theAndover, Massachusetts facility. The increase was partially offset by the maturity of available-for-sale securities of $134.9 million and restricted investmentsof $7.3 million that were purchased in 2013.Financing Activities.Cash provided by financing activities in 2015 increased by $43.7 million compared to 2014. In October 2015, we sold approximately 3.3 millionshares of common stock at an offering price of $39.00 per share. After deducting the underwriting discounts and offering related transaction costs, wereceived aggregate net proceeds of approximately $119.9 million, $25.4 million higher than prior year equity financings. Additionally, we received netproceeds of $19.6 million from the senior secured term loan and an incremental $9.0 million from option exercises. The increases were partially offset by a$2.5 million repayment of the promissory note related to our Andover, Massachusetts facility and a decrease of $7.8 million from warrant exercises thatoccurred in 2014.Cash provided by financing activities in 2014 decreased by $41.5 million compared to 2013. In April 2014, we sold approximately 2.7 million sharesof common stock at an offering price of $38.00 per share. After deducting the underwriting discounts and offering related transaction costs, we receivedaggregate net proceeds of approximately $94.5 million, $30.6 million lower than prior year equity financings. Additionally, there were decreases of $10.8million from warrant exercises and $1.7 million from option exercises. These were partially offset by $1.0 million from the employee stock purchase program.-52- Off-Balance Sheet ArrangementsDuring the periods presented, we did not have any relationships with unconsolidated entities or financial partnerships, such as entities often referred toas structured finance or special purpose entities, which would have been established for the purpose of facilitating off-balance sheet arrangements or foranother contractually narrow or limited purpose.Contractual Payment ObligationsIn our continuing operations, we have entered into long-term contractual arrangements from time to time for our facilities, the provision of goods andservices, and acquisition of technology access rights, among others. The following table presents contractual obligations arising from these arrangements asof December 31, 2015: Payment Due by Period Total Less Than1 Year 1 - 3 Years 3 - 5 Years More than5 Years (in thousands) Senior Secured Term Loan (1) $22,426 $6,494 $15,932 $— $— Long-term Mortgage Loans (1) 1,908 171 343 343 1,051 Notes payable (1) 2,504 2,504 — — — Lease obligations 24,804 4,616 9,584 10,064 540 Purchase obligations (2) 130,035 60,442 58,185 11,408 — Total contractual obligations and contingencies $181,677 $74,227 $84,044 $21,815 $1,591 (1)Interest is included.(2)Purchase obligations include agreements to purchase goods or services that are enforceable and legally binding or subject to cancellation fees and thatspecify all significant terms. Purchase obligations relate primarily to our DMD development program.Milestone ObligationsWe are obligated to make up to $95.2 million of future development, upfront royalty and commercial milestone payments associated with some of ourcollaboration and license agreements. Payments under these agreements generally become due and payable upon achievement of certain development,regulatory or commercial milestones. Because the achievement of these milestones had not occurred as of December 31, 2015, such contingencies have notbeen recorded in our financial statements. Amounts related to contingent milestone payments are not considered contractual obligations as they arecontingent on the successful achievement of certain development, regulatory approval and commercial milestones.Recent Accounting PronouncementsPlease read Note 2, Summary of Significant Accounting Policies and Recent Accounting Pronouncements to the consolidated financial statementsincluded elsewhere in this Annual Report on Form 10-K. Item 7A. Quantitative and Qualitative Disclosures About Market Risk.Our current investment policy is to maintain a diversified investment portfolio consisting of money market investments, commercial paper,government and government agency bonds and high-grade corporate bonds with maturities of 36 months or less. Our cash is deposited in and investedthrough highly rated financial institutions in North America. As of December 31, 2015, we had $204.0 million of cash, cash equivalents and investments,comprised of $80.3 million of cash and cash equivalents, $112.2 million short-term investments and $11.5 million of restricted cash and investments. The fairvalue of cash equivalents and short-term investments is subject to change as a result of potential changes in market interest rates. The potential change in fairvalue for interest rate sensitive instruments has been assessed on a hypothetical 10 basis point adverse movement across all maturities. For each of the yearsended December 31, 2015 and 2014, we estimate that such hypothetical adverse 10 basis point movement would result in a hypothetical loss in fair value ofless than $0.1 million to our interest rate sensitive instruments. -53-Item 8. Financial Statements and Supplementary Data.The information required by this Item 8 begins on page F-1 in Item 15 of Part IV of this Annual Report on Form 10-K and is incorporated into this itemby reference. Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.None. Item 9A. Controls and Procedures.Disclosure Controls and ProceduresWe carried out an evaluation as of the end of the period covered by this Annual Report on Form 10-K, under the supervision and with the participationof our management, including our principal executive officer and principal financial officer, of the effectiveness of our disclosure controls and procedurespursuant to paragraph (b) of Rule 13a-15 and 15d-15 under the Exchange Act. Based on that review, the principal executive officer and principal financialofficer have concluded that our disclosure controls and procedures are effective to ensure that information required to be disclosed by us in the reports we fileor submit under the Exchange Act (1) is recorded, processed, summarized, and reported within the time periods specified in the SEC rules and forms, and (2) isaccumulated and communicated to our management, including our principal executive officer and principal financial officer, as appropriate to allow timelydecisions regarding required disclosure.We do not expect that our disclosure controls and procedures will prevent all error and all fraud. A control procedure, no matter how well conceivedand operated, can provide only reasonable, not absolute, assurance that the objectives of the control procedure are met. Because of the inherent limitations inall control procedures, no evaluation of controls can provide absolute assurance that all control issues and instances of fraud, if any, within our companyhave been detected. These inherent limitations include the realities that judgments in decision making can be faulty, and that breakdowns can occur becauseof simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, by collusion of two or more people, or bymanagement override of the control. We considered these limitations during the development of our disclosure controls and procedures, and will continuallyreevaluate them to ensure they provide reasonable assurance that such controls and procedures are effective.Internal Control over Financial ReportingManagement’s Annual Report on Internal Control over Financial ReportingManagement is responsible for establishing and maintaining adequate internal control over financial reporting for our company, as such term isdefined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act.Our internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting andthe preparation of financial statements for external purposes in accordance with generally accepted accounting principles, and includes those policies andprocedures that: ·pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of our assets; ·provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance withgenerally accepted accounting principles, and that our receipts and expenditures are being made only in accordance with authorizations of ourmanagement and directors; and ·provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of our assets that couldhave a material effect on our financial statements.Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of anyevaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degreeof compliance with the policies or procedures may deteriorate. Management assessed the effectiveness of our internal control over financial reporting as ofDecember 31, 2015. In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the TreadwayCommission (“COSO”) in its 2013 Internal Control Integrated Framework.Based on this assessment, management has concluded that, as of December 31, 2015, our internal control over financial reporting was effective basedon those criteria.-54-The effectiveness of our internal control over financial reporting as of December 31, 2015 has been audited by KPMG LLP, an independent registeredpublic accounting firm, as stated in their report which appears in this Annual Report on Form 10-K.Changes in Internal Control over Financial ReportingThere have not been any changes in our internal control over financial reporting as defined in Rules 13a–15(f) and 15d–15(f) under the Exchange Actfor the quarter ended December 31, 2015 that our certifying officers concluded materially affected, or are reasonably likely to materially affect, our internalcontrol over financial reporting.-55-Report of Independent Registered Public Accounting FirmThe Board of Directors and StockholdersSarepta Therapeutics, Inc.: We have audited Sarepta Therapeutics, Inc.’s and subsidiaries internal control over financial reporting as of December 31, 2015, based on criteriaestablished in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO).Sarepta Therapeutics, Inc.’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of theeffectiveness of internal control over financial reporting, included in the accompanying Management’s Annual Report on Internal Control over FinancialReporting. Our responsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We conducted our audit in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standardsrequire that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained inall material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weaknessexists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audit also included performingsuch other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion. A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financialreporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’sinternal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail,accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded asnecessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of thecompany are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assuranceregarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on thefinancial statements. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of anyevaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degreeof compliance with the policies or procedures may deteriorate. In our opinion, Sarepta Therapeutics, Inc. and subsidiaries maintained, in all material respects, effective internal control over financial reporting asof December 31, 2015, based on criteria established in Internal Control – Integrated Framework (2013) issued by the Committee of Sponsoring Organizationsof the Treadway Commission (COSO). We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), the consolidatedbalance sheets of Sarepta Therapeutics, Inc. and subsidiaries as of December 31, 2015 and 2014, and the related consolidated statements of operations andcomprehensive loss, stockholders’ equity, and cash flows for each of the years in the three-year period ended December 31, 2015, and our report datedFebruary 25, 2016 expressed an unqualified opinion on those consolidated financial statements. (signed) KPMG LLP Cambridge, MassachusettsFebruary 25, 2016-56-Item 9B. Other Information.None. -57-PART III Item 10. Directors, Executive Officers and Corporate Governance.The information regarding our directors and executive officers required by this item will be included in either an amendment to this Annual Report onForm 10-K or in our definitive proxy statement for our 2016 annual meeting of stockholders to be filed with the Commission not later than 120 days after theend of the fiscal year covered by this Annual Report on Form 10-K and is incorporated herein by reference. Item 11. Executive Compensation.The information required by this item will be included in either an amendment to this Annual Report on Form 10-K or in our definitive proxystatement for our 2016 annual meeting of stockholders to be filed with the Commission not later than 120 days after the end of the fiscal year covered by thisAnnual Report on Form 10-K and is incorporated herein by reference. Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.The information required by this item will be included in either an amendment to this Annual Report on Form 10-K or in our definitive proxystatement for our 2016 annual meeting of stockholders to be filed with the Commission not later than 120 days after the end of the fiscal year covered by thisAnnual Report on Form 10-K and is incorporated herein by reference. Item 13. Certain Relationships and Related Transactions, and Director Independence.The information required by this item will be included in either an amendment to this Annual Report on Form 10-K or in our definitive proxystatement for our 2016 annual meeting of stockholders to be filed with the Commission not later than 120 days after the end of the fiscal year covered by thisAnnual Report on Form 10-K and is incorporated herein by reference. Item 14. Principal Accounting Fees and Services.The information required by this item will be included in either an amendment to this Annual Report on Form 10-K or in our definitive proxystatement for our 2016 annual meeting of stockholders to be filed with the Commission not later than 120 days after the end of the fiscal year covered by thisAnnual Report on Form 10-K and is incorporated herein by reference. -58-PART IV Item 15. Exhibits, Financial Statement Schedules.(a) The following documents are filed as part of this Annual Report on Form 10-K:(1) Financial StatementsThe following consolidated financial statements of the Company and the Report of KPMG LLP, Independent Registered Public Accounting Firm, areincluded in Part IV of this Annual Report on Form 10-K on the pages indicated: Report of Independent Registered Public Accounting FirmF-2Consolidated Balance SheetsF-3Consolidated Statements of Operations and Comprehensive LossF-4Consolidated Statements of Stockholders’ EquityF-5Consolidated Statements of Cash FlowsF-6Notes to Consolidated Financial StatementsF-7 (2) Financial Statement SchedulesAll schedules are omitted because they are not applicable or the required information is shown in the consolidated financial statements or the notesthereto.(3) ExhibitsThe exhibits required by Item 601 of Regulation S-K are listed in paragraph (b) below.(b) Exhibits.The following exhibits are filed herewith or are incorporated by reference to exhibits filed with the SEC: ExhibitNumber Description Incorporated by Reference to Filings Indicated Form File No. Exhibit FilingDate ProvidedHerewith 2.1 Agreement and Plan of Merger dated June 6, 2013 between SareptaTherapeutics, Inc., a Delaware corporation, and SareptaTherapeutics, Inc., an Oregon corporation. 8-K12B 001-14895 2.1 6/6/13 3.1 Amended and Restated Certificate of Incorporation. 8-K12B 001-14895 3.1 6/6/13 3.2 Amendment to the Amended and Restated Certificate ofIncorporation. 8-K 001-14895 3.1 6/30/15 3.3 Amended and Restated Bylaws. 8-K 001-14895 3.1 9/25/14 4.1 Form of Specimen Certificate for Common Stock. 10-Q 001-14895 4.1 8/8/13 4.2 Form of Common Stock Purchase Warrant, issued on January 30,2009. 8-K 001-14895 4.4 1/30/09 4.3 Form of Common Stock Purchase Warrant, issued on August 25,2009. 8-K 001-14895 4.1 8/24/09 10.1† Employment Agreement with Patrick Iversen, Ph.D., dated July 14,1997. 10KSB 000-22613 10.12 3/30/98 10.2† Amendment to Employment Agreement with Patrick Iversen,Ph.D., dated December 28, 2008. 10-K 001-14895 10.5 3/15/11 10.3† Amendment No. 2 to Employment Agreement with Patrick Iversen,Ph.D., dated January 18, 2010. 10-K 001-14895 10.6 3/15/11 10.4† Amended and Restated Executive Employment Agreement datedApril 19, 2013 by and between Sarepta Therapeutics, Inc. andChristopher Garabedian. 10-Q 001-14895 10.2 5/9/13 -59-ExhibitNumber Description Incorporated by Reference to Filings Indicated Form File No. Exhibit FilingDate ProvidedHerewith 10.5† Executive Employment Agreement dated January 10, 2011 byand between AVI BioPharma, Inc. and Effie Toshav. 10-Q 001-14895 10.1 5/10/11 10.6† Executive Employment Agreement dated March 29, 2011 by andbetween AVI BioPharma, Inc. and Peter S. Linsley, Ph.D. 10-Q 001-14895 10.4 5/10/11 10.7† Executive Employment Agreement dated June 13, 2011 by andbetween AVI BioPharma, Inc. and Edward Kaye, M.D. 10-Q 001-14895 10.4 8/8/11 10.8† Stand Alone Stock Option Grant between AVI BioPharma, Inc.and Effie Toshav dated January 10, 2011. 10-Q 001-14895 10.2 5/10/11 10.9† Stand Alone Stock Option Grant between the Registrant and PeterLinsley dated May 16, 2011. S-8 333-175031 4.8 6/20/11 10.10† Stand Alone Stock Option Grant between the Registrant andEdward Kaye dated June 20, 2011. S-8 333-175031 4.9 6/20/11 10.11† AVI BioPharma, Inc. 2002 Equity Incentive Plan. Schedule 14A 001-14895 Appendix A 4/11/02 10.12† Amended and Restated Sarepta Therapeutics, Inc. 2011 EquityIncentive Plan. 8-K 001-14895 10.1 6/16/11 10.13† Form of Stock Option Award Agreement under the Amended andRestated 2011 Equity Incentive Plan. 10-Q 001-14895 10.5 8/8/13 10.14† Form of Notice of Grant of Restricted Stock under the Amendedand Restated 2011 Equity Incentive Plan. 10-Q 001-14895 10.4 8/8/13 10.15† AVI BioPharma, Inc. Non-Employee Director CompensationPolicy. 8-K 001-14895 10.85 10/1/10 10.16† Form of Indemnification Agreement. 8-K 001-14895 10.86 10/8/10 10.17† Form of Restricted Stock Unit Award Agreement under 2011Equity Incentive Plan. 8-K 001-14895 10.1 4/25/12 10.18† Form of Stock Appreciate Right Award Agreement under the2011 Equity Incentive Plan. 10-Q 001-14895 10.2 11/7/12 10.19† Form of Senior Vice President Change in Control and SeveranceAgreement. 10-K 001-14895 10.19 3/15/13 10.20† Form of Vice President Change in Control and SeveranceAgreement. 10-K 001-14895 10.20 3/15/13 10.21† 2013 Employee Stock Purchase Plan. 8-K12B 001-14895 10.2 6/6/13 10.22† Executive Employment Agreement with Jayant Aphale, Ph.D. 10-Q 001-14895 10.1 8/8/13 10.23† Retention and Severance Benefits Letter Agreement dated May 9,2013 by and between the Company and Michael A. Jacobsen. 10-Q 001-14895 10.3 5/9/13 10.24† Offer Letter dated October 23, 2013 by and between SareptaTherapeutics, Inc. and Sandesh Mahatme. 10-K 001-14895 10.24 3/3/14 -60-ExhibitNumber Description Incorporated by Reference to Filings Indicated Form File No. Exhibit FilingDate ProvidedHerewith 10.25† Offer Letter dated October 23, 2012 by and between SareptaTherapeutics, Inc. and David Tyronne Howton. 10-K 001-14895 10.25 3/3/14 10.26† Executive Inducement Stock Option Agreement between ArthurKrieg and Sarepta Therapeutics, Inc. 10-K 001-14895 10.26 3/3/14 10.27† Sarepta Therapeutics, Inc. 2014 Employment CommencementIncentive Plan. 10-K 001-14895 10.27 3/3/14 10.28 Form of Stock Option Award Agreement under 2014 EmploymentCommencement Incentive Plan 10-K 001-14895 10.28 3/3/14 10.29* Collaboration and License Agreement between IsisPharmaceuticals and Ercole Biotech, Inc. dated May 16, 2003. 10-K 001-14895 10.78 3/16/10 10.30* Amended and Restated Exclusive License Agreement by andamong The University of Western Australia, SareptaTherapeutics, Inc. Sarepta International CV dated April 10,2013. 10-Q 001-14895 10.1 5/9/13 10.31 Agreement between AVI BioPharma, Inc. and the U.S. DefenseThreat Reduction Agency dated May 5, 2009. 10-Q 001-14895 10.72 8/10/09 10.32 Amendment of Contract between AVI BioPharma, Inc. and the U.S.Defense Threat Reduction Agency (contract no. HDTRA1-07-C-0010), effective May 29, 2009. 10-Q 001-14895 10.74 8/10/09 10.33 Amendment of Contract between AVI BioPharma, Inc. and the U.S.Defense Threat Reduction Agency (contract no. HDTRA 1-07-C0010), effective September 30, 2009. 10-Q 001-14895 10.77 11/9/09 10.34* Amendment of Contract between AVI BioPharma, Inc. and the U.S.Defense Threat Reduction Agency (contract no HDTRA 1-09-C-0046), effective March 25, 2010. 10-Q 001-14895 10.81 5/10/10 10.35* Contract Number HDTRA1-10-C-0079 between Defense ThreatReduction Agency and AVI BioPharma, Inc. dated June 4,2010. 10-Q 001-14895 10.84 8/9/10 10.36* Modification No. PZ0001 to Contract Number HDTRA1-10-C-0079 between Defense Threat Reduction Agency and AVIBioPharma, Inc. effective March 3, 2011. 10-Q 001-14895 10.3 5/10/11 10.37* Modification No. P00005 to Contract Number HDTRA1-10-C-0079 between Defense Threat Reduction Agency and AVIBioPharma, Inc. effective April 13, 2011. 10-Q 001-14895 10.1 8/8/11 10.38* Contract Number W9113M-10-C-0056 between U.S. Army Spaceand Missile Defense Command and AVI BioPharma, Inc. datedJuly 14, 2010. 10-Q 001-14895 10.86 11/9/10 10.39* Contract Number W911QY-12-C-0117 between U.S. Departmentof Defense’s Joint Project Manager Transformational MedicalTechnologies and Sarepta Therapeutics, Inc. dated August 23,2012. 10-Q 001-14895 10.1 11/7/12 -61-ExhibitNumber Description Incorporated by Reference to Filings Indicated Form File No. Exhibit FilingDate ProvidedHerewith 10.40* Modification No. P00005 to Contract Number W9113M-10-C-0056 between U.S. Army Space and Missile DefenseCommand and AVI BioPharma, Inc. effective August 15,2011. 10-Q/A 001-14895 10.3 2/15/12 10.41* Sponsored Research Agreement between AVI BioPharma, Inc.and Charley’s Fund, Inc., effective October 12, 2007. 10-K 001-14895 10.58 3/17/08 10.42* First Amendment to Sponsored Research Agreement betweenAVI BioPharma, Inc. and Charley’s Fund, Inc. dated June 2,2009. 10-Q 001-14895 10.75 8/10/09 10.43 Commercial Lease between Research Way Investments,Landlord, and Antivirals, Inc., Tenant, effective June 15,1992. SB-2 333-20513 10.9 1/28/97 10.44 Lease Extension and Modification Agreement datedSeptember 1, 1996, by and between Research WayInvestments and Antivirals, Inc. 10-K 001-14895 10.53 3/15/11 10.45 Second Lease Extension and Modification Agreement datedJanuary 24, 2006 by and between Research Way Investmentsand AVI BioPharma, Inc. 10-Q 001-14895 10.55 8/9/06 10.46 Real Property Purchase Agreement by and between WKLInvestments Airport, LLC and AVI BioPharma, Inc., datedMarch 1, 2007, as amended. 10-Q 001-14895 10.61 8/9/07 10.47 Lease Agreement between AVI BioPharma, Inc. and PerpetuaPower Source Technologies, Inc., dated November 23, 2011. 10-K 001-14895 10.42 3/13/12 10.48 First Amendment to Lease Agreement dated December 22, 2011between AVI BioPharma, Inc. and Perpetua Power SourceTechnologies, Inc. 10-K 001-14895 10.43 3/13/12 10.49 Second Amendment to Lease Agreement dated January 20, 2012between AVI BioPharma, Inc. and Perpetua Power SourceTechnologies, Inc. 10-K 001-14895 10.44 3/13/12 10.50 Lease dated July 27, 2009 by and between BMR-3450 MonteVilla Parkway, LLC and AVI BioPharma, Inc. 10-Q 001-14895 10.76 11/9/09 10.51 First Amendment to Lease dated August 30, 2011 by andbetween BMR-3450 Monte Villa Parkway LLC and AVIBioPharma, Inc. 10-Q 001-14895 10.4 11/8/11 10.52 Second Amendment to Lease dated January 31, 2012 by andbetween BMR-3450 Monte Villa Parkway LLC and AVIBioPharma, Inc. 10-K 001-14895 10.47 3/13/12 10.53 Third Amendment to Lease dated May 31, 2012 by and betweenBMR-3450 Monte Villa Parkway LLC and AVI BioPharma,Inc. 10-Q 001-14895 10.2 8/7/12 10.54 Lease dated October 20, 2010, by and between S/I North CreekVII LLC and AVI BioPharma, Inc. 10-K 001-14895 10.57 3/15/11 10.55 Lease Agreement dated June 25, 2013 by and between SareptaTherapeutics, Inc. and ARE-MA Region No. 38, LLC. 8-K 001-14895 10.1 7/1/13 -62-ExhibitNumber Description Incorporated by Reference to Filings Indicated Form File No. Exhibit FilingDate ProvidedHerewith 10.56 Purchase and Sale Agreement dated May 22, 2014between Sarepta Therapeutics, Inc. and Eisai Inc. 10-Q 001-14895 10.1 8/7/14 10.57 Offer Letter dated January 6, 2014 by and between SareptaTherapeutics, Inc. and Arthur Krieg, M.D. 10-Q 001-14895 10.1 5/8/14 10.58† Employment Agreement dated April 20, 2015 between SareptaTherapeutics, Inc. and Edward Kaye 10-Q 001-14895 10.1 5/7/15 10.59 Credit and Security Agreement between Sarepta Therapeutics,Inc. and MidCap Financial dated June 26, 2015 10-Q 001-14895 10.1 8/6/15 10.60 Pledge Agreement between Sarepta Therapeutics, Inc. andMidCap Financial dated June 26, 2015 10-Q 001-14895 10.2 8/6/15 10.61† Separation and Consulting Agreement and General Releasebetween Sarepta Therapeutics, Inc. and ChristopherGarabedian entered into on June 30, 2015 10-Q 001-14895 10.3 8/6/15 10.62† Amendment No. 1 to the Sarepta Therapeutics, Inc. Amended andRestated 2011 Equity Incentive Plan 8-K 001-14895 10.1 6/30/15 21.1 Subsidiaries of the Registrant. X 23.1 Consent of Independent Registered Public Accounting Firm. X 24.1 Power of Attorney (contained on signature page). X 31.1 Certification of the Company’s Interim Chief Executive Officerand Chief Medical Officer, Edward Kaye, MD, pursuant toSection 302 of the Sarbanes-Oxley Act of 2002. X 31.2 Certification of the Company’s Senior Vice President, ChiefFinancial Officer, Sandesh Mahatme, pursuant to Section 302of the Sarbanes-Oxley Act of 2002. X 32.1** Certification of the Company’s Interim Chief Executive Officerand Chief Medical Officer, Edward Kaye, MD, pursuant toSection 906 of the Sarbanes-Oxley Act of 2002. X 32.2** Certification of the Company’s Senior Vice President, ChiefFinancial Officer, Sandesh Mahatme, pursuant to Section 906of the Sarbanes-Oxley Act of 2002. X 101.INS XBRL Instance Document. X 101.SCH XBRL Taxonomy Extension Schema Document. X 101.CAL XBRL Taxonomy Extension Calculation Linkbase Document. X 101.DEF XBRL Taxonomy Extension Definition Linkbase Document. X 101.LAB XBRL Taxonomy Extension Label Linkbase Document. X 101.PRE XBRL Taxonomy Extension Presentation Linkbase Document. X †Indicates management contract or compensatory plan, contract or arrangement.*Confidential treatment has been granted for portions of this exhibit.**Furnished herewith. -63-SIGNATURESPursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed onits behalf by the undersigned, thereunto duly authorized. Dated: February 25, 2016 SAREPTA THERAPEUTICS, INC. By:/s/ Edward Kaye, MD Edward Kaye, MD Interim Chief Executive Officer, Senior Vice President, Chief MedicalOfficer POWER OF ATTORNEYKNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Edward Kaye, MD andSandesh Mahatme, and each of them, with full power of substitution and resubstitution and full power to act without the other, as his or her true and lawfulattorney-in-fact and agent to act in his or her name, place and stead and to execute in the name and on behalf of each person, individually and in eachcapacity stated below, and to file, any and all documents in connection therewith, with the Securities and Exchange Commission, granting unto saidattorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing, ratifying and confirming all that saidattorneys-in-fact and agents or any of them or their and his or her substitute or substitutes, may lawfully do or cause to be done by virtue thereof.Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of theregistrant and in the capacities indicated on February 25, 2016: Signature Title /s/ Edward Kaye, MD Interim Chief Executive Officer, Senior Vice President, Chief MedicalOfficer (Principal Executive Officer)Edward Kaye, MD /s/ Sandesh Mahatme Senior Vice President, Chief Financial Officer (Principal Financialand Accounting Officer)Sandesh Mahatme /s/ M. Kathleen Behrens Chairwoman of the BoardM. Kathleen Behrens, Ph.D. /s/ Richard Barry DirectorRichard Barry /s/ Jean-Paul Kress, MD DirectorJean-Paul Kress, MD /s/ William Goolsbee DirectorWilliam Goolsbee /s/ Claude Nicaise, MD DirectorClaude Nicaise, MD /s/ Gil Price DirectorGil Price, M.D. /s/ Hans Wigzell DirectorHans Wigzell, M.D., Ph.D. -64-SAREPTA THERAPEUTICS, INC.CONSOLIDATED FINANCIAL STATEMENTS PageNumberReport of Independent Registered Public Accounting Firm F-2Consolidated Balance Sheets F-3Consolidated Statements of Operations and Comprehensive Loss F-4Consolidated Statements of Stockholders’ Equity F-5Consolidated Statements of Cash Flows F-6Notes to Consolidated Financial Statements F-7 F-1Report of Independent Registered Public Accounting FirmThe Board of Directors and StockholdersSarepta Therapeutics, Inc.: We have audited the accompanying consolidated balance sheets of Sarepta Therapeutics, Inc. and subsidiaries as of December 31, 2015 and 2014,and the related consolidated statements of operations and comprehensive loss, stockholders’ equity, and cash flows for each of the years in the three yearperiod ended December 31, 2015. These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is toexpress an opinion on these consolidated financial statements based on our audits. We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standardsrequire that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. An auditincludes examining, on a test basis, evidence supporting the amounts and disclosures in the financial statements. An audit also includes assessing theaccounting principles used and significant estimates made by management, as well as evaluating the overall financial statement presentation. We believe thatour audits provide a reasonable basis for our opinion. In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of SareptaTherapeutics, Inc. and subsidiaries as of December 31, 2015 and 2014, and the results of its operations and its cash flows for each of the years in the three yearperiod ended December 31, 2015, in conformity with U.S. generally accepted accounting principles. We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States), Sarepta Therapeutics,Inc. and subsidiaries’ internal control over financial reporting as of December 31, 2015, based on criteria established in Internal Control – IntegratedFramework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO), and our report dated February 25, 2016expressed an unqualified opinion on the effectiveness of the Company’s internal control over financial reporting. (signed) KPMG LLP Cambridge, MassachusettsFebruary 25, 2016 F-2Sarepta Therapeutics, Inc.Consolidated Balance Sheets(in thousands, except share data) As ofDecember 31,2015 As ofDecember 31,2014 Assets Current Assets: Cash and cash equivalents $80,304 $73,551 Short-term investments 112,187 136,793 Accounts receivable 3,977 2,416 Restricted investment 10,695 — Other current assets 17,380 35,036 Total Current Assets 224,543 247,796 Restricted cash and investments 783 782 Property and equipment, net of accumulated depreciation of $24,594 and $19,896 as of December 31, 2015 and 2014, respectively 37,344 38,501 Patent costs, net of accumulated amortization of $2,620 and $2,081 as of December 31, 2015 and 2014, respectively 6,642 5,891 Other assets 4,470 2,063 Total Assets $273,782 $295,033 Liabilities and Stockholders’ Equity Current Liabilities: Accounts payable $20,234 $12,408 Accrued expenses 29,053 17,366 Current portion of long-term debt 5,936 98 Current portion of notes payable 2,493 2,492 Deferred revenue 3,303 3,318 Other current liabilities 1,275 1,185 Total Current Liabilities 62,294 36,867 Long-term debt 14,969 1,476 Notes payable — 2,262 Deferred rent and other 6,172 6,775 Total Liabilities 83,435 47,380 Commitments and contingencies Stockholders’ Equity: Preferred stock, $.0001 par value, 3,333,333 shares authorized; none issued and outstanding — — Common stock, $.0001 par value, 99,000,000 shares authorized; 45,629,529 and 41,311,512 issued and outstanding at December 31, 2015 and 2014, respectively 5 4 Additional paid-in capital 1,089,508 926,769 Accumulated other comprehensive loss (111) (95)Accumulated deficit (899,055) (679,025)Total Stockholders’ Equity 190,347 247,653 Total Liabilities and Stockholders’ Equity $273,782 $295,033 See accompanying notes to consolidated financial statements. F-3Sarepta Therapeutics, Inc.Consolidated Statements of Operations and Comprehensive Loss(in thousands, except per share data) For the Year Ended December 31, 2015 2014 2013 Revenue from research contracts and other grants $1,253 $9,757 $14,219 Operating expenses: Research and development 146,394 94,231 72,909 General and administrative 75,043 49,315 31,594 Total operating expenses 221,437 143,546 104,503 Operating loss (220,184) (133,789) (90,284) Other income (loss): Interest income and other, net 154 779 326 Loss on change in warrant valuation — (2,779) (22,027)Total other income (loss) 154 (2,000) (21,701) Net loss $(220,030) $(135,789) $(111,985) Other comprehensive loss: Unrealized loss on short-term securities - available-for-sale (16) (95) — Total other comprehensive loss (16) (95) — Comprehensive loss $(220,046) $(135,884) $(111,985)Net loss per share — basic and diluted $(5.20) $(3.39) $(3.31) Weighted average number of shares of common stock outstanding for computing basic and diluted net loss per share 42,290 40,026 33,850 See accompanying notes to consolidated financial statements. F-4Sarepta Therapeutics, Inc.Consolidated Statements of Stockholders’ Equity(in thousands) Accumulated Additional Other Total Common Stock Paid-In Comprehensive Accumulated Stockholders' Shares Amount Capital Loss Deficit Equity BALANCE AT DECEMBER 31, 2012 31,704 $3 $554,927 $— $(431,251) $123,679 Exercise of options for common stock 241 — 2,725 — — 2,725 Exercise of warrants for common stock 2,336 — 96,768 — — 96,768 Vest of restricted stock units 31 — — — — — Shares withheld for taxes (7) — (226) — — (226)Grant of restricted stock awards 6 — — — — — Issuance of common stock for cash, net of offering costs 3,441 1 125,103 — — 125,104 Stock-based compensation — — 11,127 — — 11,127 Net loss — — — — (111,985) (111,985)BALANCE AT DECEMBER 31, 2013 37,752 4 790,424 — (543,236) 247,192 Exercise of options for common stock 86 — 980 — — 980 Exercise of warrants for common stock 766 — 19,536 — — 19,536 Vest of restricted stock units 7 — — — — — Shares withheld for taxes (1) — (34) — — (34)Grant of restricted stock awards 6 — — — — — Issuance of common stock for cash, net of offering costs 2,650 — 94,503 — — 94,503 Issuance of common stock under employee stock purchase plan 46 — 1,015 — — 1,015 Stock-based compensation — — 20,345 — — 20,345 Unrealized loss from available-for-sale securities — — — (95) — (95)Net loss — — — — (135,789) (135,789)BALANCE AT DECEMBER 31, 2014 41,312 4 926,769 (95) (679,025) 247,653 Exercise of options for common stock 817 — 10,010 — — 10,010 Grant of restricted stock awards 181 — — — — — Shares withheld for taxes (6) — (182) — — (182)Issuance of common stock for cash, net of offering costs 3,250 1 119,915 — — 119,916 Issuance of common stock under employee stock purchase plan 76 — 879 — — 879 Stock-based compensation — — 32,117 — — 32,117 Unrealized loss from available-for-sale securities — — — (16) — (16)Net loss — — — — (220,030) (220,030)BALANCE AT DECEMBER 31, 2015 45,630 $5 $1,089,508 $(111) $(899,055) $190,347 See accompanying notes to consolidated financial statements. F-5Sarepta Therapeutics, Inc.Consolidated Statements of Cash Flows(in thousands) For the Year Ended December 31, 2015 2014 2013 Cash flows from operating activities: Net loss $(220,030) $(135,789) $(111,985)Adjustments to reconcile net income to cash flows in operating activities: Depreciation and amortization 5,247 3,690 1,277 Amortization of premium on available-for-sale securities 652 2,432 — Non-cash interest 367 12 — Loss on abandonment of patents 197 128 590 Stock-based compensation 32,117 20,345 11,127 Increase in warrant valuation — 2,779 22,027 Changes in operating assets and liabilities, net: Net (increase) decrease in accounts receivable (1,561) 1,114 1,183 Net decrease (increase) in other assets 15,249 (34,013) 1,618 Net increase in accounts payable, accrued expenses, deferred revenue and other liabilities 18,297 10,763 9,468 Net cash used in operations (149,465) (128,539) (64,695) Cash flows from investing activities: Release and maturity of restricted investments — 7,250 — Purchase of restricted investments (10,695) — (7,897)Purchase of property and equipment (3,401) (25,444) (2,370)Patent costs (1,432) (1,381) (1,405)Purchase of available-for-sale securities (162,001) (274,368) — Maturity of available-for-sale securities 185,939 134,913 — Net cash from (used in) investing activities 8,410 (159,030) (11,672) Cash flows from financing activities: Proceeds from borrowings, net of debt issuance costs 19,601 — — Repayments of long-term debt and notes payable (2,598) (94) (89)Proceeds from exercise of options and warrants and the sale of common stock, net of offering costs 130,805 104,249 145,986 Other financing activities, net — — (226)Net cash from financing activities 147,808 104,155 145,671 Increase (decrease) in cash and cash equivalents 6,753 (183,414) 69,304 Cash and cash equivalents: Beginning of period 73,551 256,965 187,661 End of period 80,304 73,551 256,965 Supplemental disclosure of cash flow information: Cash paid during the period for interest $769 $77 $144 Supplemental schedule of non-cash investing activities and financing activities: Accrued debt issuance costs related to the senior secured term loan $400 $— $— Property and equipment included in accrued expenses $318 $277 $3,964 Patent costs included in accrued expenses $335 $270 $195 Capitalized interest $99 $137 $— Issuance of common stock in satisfaction of warrants $— $11,785 $78,214 Tenant improvement paid by Landlord $— $153 $6,214 Issuance of note payable in relation to the purchase of certain real and personal property located in Andover, Massachusetts $— $4,613 $— See accompanying notes to consolidated financial statements. F-6Sarepta Therapeutics, Inc.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 1. ORGANIZATION AND NATURE OF BUSINESSSarepta Therapeutics, Inc. (together with its wholly-owned subsidiaries “Sarepta” or the “Company”) is a biopharmaceutical company focused on thediscovery and development of unique RNA-targeted therapeutics for the treatment of rare, infectious and other diseases. Applying its proprietary, highly-differentiated and innovative platform technologies, the Company is able to target a broad range of diseases and disorders through distinct RNA-targetedmechanisms of action. The Company is primarily focused on rapidly advancing the development of its potentially disease-modifying Duchenne musculardystrophy (“DMD”) drug candidates, including its lead DMD product candidate, eteplirsen, designed to skip exon 51. On August 25, 2015, the Companyannounced the filing by the Food and Drug Administration (“FDA”) of its new drug application (“NDA”) for eteplirsen for the treatment of DMD amenable toexon 51 skipping. Eteplirsen is under priority review with a current Prescription Drug User Fee Act (“PDUFA”) action date of May 26, 2016. The Company isalso developing therapeutics using its technology for the treatment of drug resistant bacteria and infectious, rare and other human diseases.The Company has not generated any revenue from product sales to date and there can be no assurance that revenue from product sales will beachieved. Even if it does achieve revenue from product sales, the Company is likely to continue to incur operating losses in the near term.As of December 31, 2015, the Company had approximately $204.0 million of cash, cash equivalents and investments, consisting of $80.3 million ofcash and cash equivalents, $112.2 million of short-term investments and $11.5 million of restricted cash and investments. The Company believes that itsbalance of cash, cash equivalents and investments as of December 31, 2015 is sufficient to fund its current operational plan for at least the next twelvemonths, though it may pursue additional cash resources through public or private financings, seek additional government contracts and establishcollaborations with or license its technology to other companies. 2. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES AND RECENT ACCOUNTING PRONOUNCEMENTSBasis of PresentationThe accompanying consolidated financial statements, which have been prepared in accordance with accounting principles generally accepted in theUnited States (“U.S. GAAP”), reflect the accounts of Sarepta Therapeutics, Inc. and its wholly-owned subsidiaries. All intercompany transactions between andamong its consolidated subsidiaries have been eliminated. Management has determined that the Company operates in one segment: the development ofpharmaceutical products on its own behalf or in collaboration with others.Estimates and UncertaintiesThe preparation of the consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions thataffect the reported amounts of assets, liabilities, equity, revenue, expenses and the disclosure of contingent assets and liabilities. Actual results could differfrom those estimates. Significant items subject to such estimates and assumptions include the valuation of stock-based awards, research and developmentexpenses, income tax and revenue recognition.Fair Value MeasurementsThe Company has certain financial assets that are recorded at fair value which have been classified as Level 1, 2 or 3 within the fair value hierarchy asdescribed in the accounting standards for fair value measurements: ·Level 1—quoted prices for identical instruments in active markets; ·Level 2—quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets that are notactive, and model-derived valuations in which all significant inputs and significant value drivers are observable in active markets; and ·Level 3—valuations derived from valuation techniques in which one or more significant value drivers are unobservable.The fair value of most of the Company’s financial assets is categorized as Level 2 within the fair value hierarchy. These financial assets have beeninitially valued at the transaction price and subsequently valued, at the end of each reporting period, throughF-7income-based approaches utilizing market observable data. For additional information related to fair value measurements, please read Note 4, Fair ValueMeasurements to the consolidated financial statements.Cash and Cash EquivalentsOnly investments that are highly liquid and readily convertible to cash and have original maturities of three months or less are considered cashequivalents. As of December 31, 2015, cash equivalents were comprised of money market funds and commercial paper.Available-For-Sale Debt SecuritiesAvailable-for-sale debt securities are recorded at fair market value and unrealized gains and losses are included in accumulated other comprehensiveloss in stockholder’s equity. Realized gains and losses are reported in interest income and other, net, on a specific identification basis.Accounts ReceivableThe Company’s accounts receivable primarily arise from government research contracts and other grants. They are generally stated at invoiced amountand do not bear interest. Because the accounts receivable are primarily from government agencies and historically no amounts have been written off, anallowance for doubtful accounts receivable is not considered necessary. The balance for unbilled receivables for the years ended December 31, 2015 and2014 was $4.0 million and $2.4 million, respectively, all of which is subject to government audit and will not be collected until the completion of the audit.The increase in unbilled receivables is related to contract finalization of the Ebola portion of the July 2010 Department of Defense contract.Property and EquipmentProperty and equipment are initially recorded at cost, including the acquisition cost and all costs necessarily incurred to bring the asset to the locationand working condition necessary for its intended use. The cost of normal, recurring or periodic repairs and maintenance activities related to property andequipment are expensed as incurred. The cost for planned major maintenance activities, including the related acquisition or construction of assets, iscapitalized if the repair will result in future economic benefits. Interest costs incurred during the construction period of major capital projects are capitalizeduntil the asset is ready for its intended use, at which point the interest costs are amortized as depreciation expense over the life of the underlying asset.The Company generally depreciates the cost of its property and equipment using the straight-line method over the estimated useful lives of therespective assets, which are summarized as follows: Asset Category Useful livesLab equipment 5 yearsOffice equipment 5 yearsSoftware and computer equipment 5 yearsLeasehold improvements Lesser of the useful life or the term of the respective leaseLand Not depreciatedBuilding 30 yearsConstruction in Progress Not depreciated until put into service Patent CostsPatent costs consist primarily of external legal costs, filing fees incurred to file patent applications and renewal fees on proprietary technologydeveloped or licensed by the Company. Patent costs associated with applying for a patent, being issued a patent and annual renewal fees are capitalized.Costs to defend a patent and costs to invalidate a competitor’s patent or patent application are expensed as incurred. Patent costs are amortized on a straight-line basis over the shorter of the estimated economic lives or the initial term of the patents, generally 20 years. Patent amortization expense was $0.5 million,$0.5 million and $0.4 million for the years ended December 31, 2015, 2014 and 2013, respectively. The Company also expensed the remaining net bookvalue of previously capitalized patents that were later abandoned of $0.2 million, $0.1 million and $0.5 million for the year ended December 31, 2015, 2014and 2013, respectively, which were included in research and development expenses on the consolidated statements of operations and comprehensive loss.F-8The following table summarizes the estimated future amortization for patent costs for the next five years: As ofDecember 31, 2015(in thousands) 2016 $565 2017 553 2018 546 2019 540 2020 510 Total $2,714 Impairment of Long-Lived AssetsLong-lived assets held and used by the Company and intangible assets with definite lives are reviewed for impairment whenever events orcircumstances indicate that the carrying amount of assets may not be recoverable. The Company evaluates recoverability of assets to be held and used bycomparing the carrying amount of an asset to future net undiscounted cash flows to be generated by the asset. If such assets are considered to be impaired, theimpairment to be recognized is measured as the amount by which the carrying amount of the assets exceeds the fair value of the assets. Such reviews assessthe fair value of the assets based upon estimates of future cash flows that the assets are expected to generate.Revenue RecognitionAll of the Company’s revenue is generated from government research contracts and other grants. The Company’s contracts with the U.S. governmentare cost plus contracts providing for reimbursed costs which include overhead and general and administrative costs and a target fee. The Company recognizesrevenue from government research contracts during the period in which the related expenses are incurred and presents such revenues and related expenses ona gross basis in the consolidated financial statements. The Company’s government contracts are subject to government audits, which may result in catch-upadjustments. As of December 31, 2014, the Company had completed all development activities under its contracts with the U.S. government. The majority ofthe revenue under government contracts was recognized as of December 31, 2015 and only revenue for contract finalization, if any, is expected in the future.If a technology, right, product or service is separate and independent of our performance under other elements of an arrangement, the Company defersrecognition of non-refundable up-front fees if it has continuing performance obligations when the technology, right, product or service conveyed inconjunction with the non-refundable fee has no utility to the licensee. In addition, if the Company has continuing involvement through research anddevelopment services that are required because of its know-how or because the services can only be performed by the Company, such up-front fees aredeferred and recognized over the period of continuing involvement. As of December 31, 2015, the Company had deferred revenue of $3.3 million, whichrepresents up-front fees which it may recognize as revenue upon settlement of certain obligations.Research and DevelopmentResearch and development expenses consist of costs associated with research activities as well as those with the Company’s product developmentefforts, conducting preclinical studies, clinical trials and manufacturing activities. Research and development expenses are expensed as incurred.Nonrefundable advance payments for goods or services that will be used or rendered for future research and development activities pursuant to an executorycontractual arrangement will be deferred and capitalized, and recognized as an expense as the related goods are delivered or the related services areperformed. If the Company does not expect the goods to be delivered or services to be rendered, the advance payment capitalized will be charged to expense.Direct research and development expenses associated with the Company’s programs include clinical trial site costs, clinical manufacturing costs, costsincurred for consultants and other external services, such as data management and statistical analysis support and materials and supplies used in support ofclinical programs. Indirect costs of the Company’s clinical programs include salaries, stock-based compensation and an allocation of its facility costs.When third-party service providers’ billing terms do not coincide with the Company’s period-end, the Company is required to make estimates of itsobligations to those third parties, including clinical trial and pharmaceutical development costs, contractual services costs and costs for supply of its drugcandidates, incurred in a given accounting period and record accruals at the end of the period. The Company bases its estimates on its knowledge of theresearch and development programs, services performed for the period, past history for related activities and the expected duration of the third party servicecontract, where applicable.F-9Stock-Based CompensationThe Company’s stock-based compensation programs include stock options, restricted stock awards (“RSAs”), restricted stock units (“RSUs”), stockappreciation rights (“SARs”) and employee stock purchase program (“ESPP”). The Company accounts for stock-based compensation using the fair valuemethod.The fair values of stock options and SARs are estimated on the date of grant using the Black-Scholes-Merton option-pricing model. The fair values ofRSAs and RSUs are based on the fair market value of the Company’s common stock on the date of the grant. The fair value of stock awards, withconsideration given to estimated forfeitures, is recognized as stock-based compensation expense on a straight-line basis over the vesting period of the grants.For stock awards with performance-vesting conditions, the Company does not recognize compensation expense until it is probable that the performance-vesting condition will be achieved.Under the Company’s ESPP, participating employees purchase common stock through payroll deductions. The purchase price is equal to 85% of thelower of the closing price of the Company’s common stock on the first business day and the last business day of the relevant purchase period. The fair valuesof stock purchase rights are estimated using the Black-Scholes-Merton option-pricing model. The fair value of the look-back provision plus the 15%discount is recognized on a graded-vesting basis as stock-based compensation expense over the purchase period.Income TaxesThe Company follows the asset and liability method of accounting for income taxes. Deferred tax assets and liabilities are recognized for the future taxconsequences attributable to differences between the consolidated financial statement carrying amounts of existing assets and liabilities and their respectivetax bases and operating loss and tax credit carryforwards. It is the intention of the Company to reinvest the earnings of its non-U.S. subsidiaries in thoseoperations and not to repatriate the earnings to the U.S. Accordingly, the Company does not provide for deferred taxes on the excess of the financial reportingover the tax basis in its investments in foreign subsidiaries as they are considered permanent in duration. To date, the Company has not had any earnings inits non-U.S. subsidiaries.Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in the years in which those temporarydifferences are expected to be recovered and settled. A valuation allowance is recorded to reduce the net deferred tax asset to zero because it is more likelythan not that the net deferred tax asset will not be realized. The Company recognizes the effect of income tax positions only if those positions are more likelythan not of being sustained upon an examination.Rent ExpenseThe Company’s operating leases for its Cambridge, Massachusetts and Corvallis, Oregon facilities provide for scheduled annual rent increasesthroughout each lease’s term. The Company recognizes the effects of the scheduled rent increases on a straight-line basis over the full term of the leases.For the year ended December 31, 2015, 2014 and 2013, the Company recognized rent expense and occupancy costs of $5.2 million, $4.4 million and$3.4 million, respectively.Commitments and ContingenciesThe Company records liabilities for legal and other contingencies when information available to the Company indicates that it is probable that aliability has been incurred and the amount of loss can be reasonably estimated. Legal costs in connection with legal and other contingencies are expensed ascosts are incurred.Subsequent EventsSubsequent events have been evaluated up through the date that these consolidated financial statements were filed and no material subsequent eventswere identified.Recent Accounting PronouncementsIn April 2015, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) No. 2015-03, “Simplifying thePresentation of Debt Issuance Costs”. The amendments in this update require that debt issuance costs related to a recognized debt liability be presented onthe balance sheet as a direct deduction from the carrying amount of that debt liability, consistent with debt discounts. ASU No. 2015-03 will be effective forfiscal years beginning after December 15, 2015, with earlyF-10adoption permitted. The Company has elected to adopt this ASU early and the adoption of this guidance did not have a material effect on its consolidatedfinancial statements.In August 2014, the FASB issued ASU No. 2014-15, “Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern”. Thisupdate requires an entity’s management to evaluate whether there are conditions or events, considered in the aggregate, that raise substantial doubt about theentity’s ability to continue as a going concern within one year after the date that the financial statements are issued or available to be issued and to providerelated disclosures. ASU No. 2014-15 is effective for the annual period ending after December 15, 2016, with early adoption permitted. The Company had notadopted this guidance as of December 31, 2015, and based on the Company's financial condition as of the date these financial statements were issued oravailable for issuance, the Company does not expect the adoption of this guidance to have any impact on the current period financial statements.In May 2014, the FASB issued ASU No. 2014-09, “Revenue from Contracts with Customers (Topic 606)”. This ASU supersedes the revenuerecognition requirements in Accounting Standards Codification Topic 605, Revenue Recognition, and creates a new Topic 606, Revenue from Contracts withCustomers. Under the new guidance, a company is required to recognize revenue when it transfers goods or renders services to customers at an amount that itexpects to be entitled to in exchange for these goods or services. This guidance is effective for the fiscal years beginning after December 15, 2016, with earlyadoption not permitted. In August 2015, the FASB issued ASU No. 2015-14, “Deferral of the Effective Date”, which states that the mandatory effective dateof this new revenue standard will be delayed by one year, with early adoption only permitted in fiscal year 2017. The Company has not yet determined whichadoption method it will utilize or the effect that the adoption of this guidance will have on its consolidated financial statements. 3. SIGNIFICANT AGREEMENTSUniversity of Western AustraliaIn April 2013, the Company and the University of Western Australia (“UWA”) entered into an agreement under which an existing exclusive licenseagreement between the Company and UWA was amended and restated (“the Amended and Restated UWA License Agreement”). The Amended and RestatedUWA License Agreement grants the Company specific rights to the treatment of DMD by inducing the skipping of certain exons. The Company’s leadclinical candidate, eteplirsen, falls under the scope of the license granted under the Amended and Restated UWA License Agreement. Any future drugcandidates developed for the treatment of DMD by exon skipping may or may not fall under the scope of the Amended and Restated UWA LicenseAgreement.Under the Amended and Restated UWA License Agreement, the Company is required to meet certain performance diligence obligations related todevelopment and commercialization of products developed under the license. The Company believes that it is currently in compliance with theseobligations. In 2013, the Company made an initial up-front payment to UWA of $1.1 million upon execution of the Amended and Restated UWA LicenseAgreement. The Company may be required to make additional payments to UWA of up to $6.0 million in aggregate based on successful achievement ofcertain regulatory and commercial milestones relating to eteplirsen and up to five additional product candidates and may also be required to pay a low-single-digit percentage royalty on net sales of products covered by issued patents licensed from UWA during the term of the Amended and Restated UWALicense Agreement. As of December 31, 2015, the Company was not under any obligation to make royalty payments to UWA until achievement of the firstcommercial sale of a product candidate that falls under the scope of the Amended and Restated UWA License Agreement.Under the Amended and Restated UWA License Agreement, the Company also has the option to purchase future royalties upfront. Under this option,the Company may be required to make to the UWA an up-front payment of $30.0 million as well as $20.0 million in aggregate contingency payment uponsuccessful achievement of certain commercial milestones. As of December 31, 2015, the Company had not made its decision whether to exercise this optionand, therefore, is not under any current obligation to make any milestone payments discussed above.Charley’s Fund AgreementIn October 2007, Charley’s Fund, Inc. (“Charley’s Fund”), a nonprofit organization that funds drug development and discovery initiatives specific toDMD, awarded the Company a research grant of approximately $2.5 million and, in May 2009, the grant authorization was increased to a total of $5.0million. Pursuant to the related sponsored research agreement, the grant was provided to support the development of product candidates related to exon 50skipping which utilize the Company’s proprietary technologies. The grant requires the Company to make a mid-single-digit percentage royalty on net salesof any such products that are successfully commercialized up to the total amount received under the grant.As of December 31, 2015, Charley’s Fund has made payments of approximately $3.4 million to the Company. Revenue associated with this researchand development arrangement is recognized based on the proportional performance method. To date, theF-11Company has recognized less than $0.1 million as revenue and did not recognize any revenue for the years ended December 31, 2015, 2014 or 2013. TheCompany does not expect to receive any incremental funding under the grant and has deferred $3.3 million of previous receipts which are anticipated to berecognized as revenue upon settlement of certain obligations. 4. FAIR VALUE MEASUREMENTSThe tables below present information about the Company’s financial assets that are measured and carried at fair value and indicate the level within thefair value hierarchy of the valuation techniques it utilizes to determine such fair value: Fair Value Measurement as of December 31, 2015 Total Level 1 Level 2 Level 3 (in thousands) Money market funds $32,850 $32,850 $— $— Commercial paper 48,899 — 48,899 — Government and government agency bonds 50,918 — 50,918 — Corporate bonds 17,370 — 17,370 — Certificates of deposit 11,343 11,343 — — Total assets $161,380 $44,193 $117,187 $— Fair Value Measurement as of December 31, 2014 Total Level 1 Level 2 Level 3 (in thousands) Money market funds $47,740 $47,740 $— $— Commercial paper 2,997 — 2,997 — Government and government agency bonds 75,250 — 75,250 — Corporate bonds 58,546 — 58,546 — Certificates of deposit 647 647 — — Total assets $185,180 $48,387 $136,793 $— The Company’s assets with fair value categorized as Level 1 within the fair value hierarchy include money market funds and certificates of deposit.Money market funds are publicly traded mutual funds and are presented as cash equivalents on the consolidated balance sheets as of December 31, 2015The Company’s assets with fair value categorized as Level 2 within the fair value hierarchy consist of commercial paper, government and governmentagency bonds and corporate bonds. These assets have been initially valued at the transaction price and subsequently valued, at the end of each reportingperiod, through income-based approaches utilizing market observable data.The carrying amounts reported in the consolidated balance sheets for cash and cash equivalents, accounts receivable and accounts payableapproximate fair value because of the immediate or short-term maturity of these financial instruments. The carrying amounts for long-term debt and notespayable approximate fair value based on market activity for other debt instruments with similar characteristics and comparable risk. F-125. CASH, CASH EQUIVALENTS AND SHORT-TERM INVESTMENTSIt is the Company’s policy to mitigate credit risk in its financial assets by maintaining a well-diversified portfolio that limits the amount of exposureas to maturity and investment type. The weighted average maturity of the Company’s available-for-sale securities as of December 31, 2015 and 2014 wasapproximately four months. The following tables summarize the Company’s cash, cash equivalents and short-term investments for each of the periodsindicated: As of December 31, 2015 AmortizedCost GrossUnrealizedGains GrossUnrealizedLosses FairMarketValue (in thousands) Cash and money market funds $75,304 $— $— $75,304 Commercial paper 48,936 — (37) 48,899 Government and government agency bonds 50,966 — (48) 50,918 Corporate bonds 17,396 — (26) 17,370 Total assets $192,602 $— $(111) $192,491 As reported: Cash and cash equivalents $80,304 $80,304 Short-term investments 112,298 (111) 112,187 Total assets $192,602 $— $(111) $192,491 As of December 31, 2014 AmortizedCost GrossUnrealizedGains GrossUnrealizedLosses FairMarketValue (in thousands) Cash and money market funds $73,551 $— $— $73,551 Commercial paper 2,997 — — 2,997 Government and government agency bonds 75,289 — (39) 75,250 Corporate bonds 58,602 — (56) 58,546 Total assets $210,439 $— $(95) $210,344 As reported: Cash and cash equivalents $73,551 $— $— $73,551 Short-term investments 136,888 — (95) 136,793 Total assets $210,439 $— $(95) $210,344 6. OTHER CURRENT ASSETSThe following table summarizes the Company’s other current assets for each of the periods indicated: As ofDecember 31,2015 As ofDecember 31,2014 (in thousands) Manufacturing-related deposits $13,070 $30,668 Prepaid expenses 3,109 2,797 Other 1,201 1,571 Total other current assets $17,380 $35,036 F-137. PROPERTY AND EQUIPMENTProperty and equipment are recorded at historical cost, net of accumulated depreciation. The following table summarizes components of property andequipment, net for each of the periods indicated: As of December 31, 2015 2014 (in thousands) Land$4,158 $4,158 Building 12,718 12,617 Software and computer equipment 6,149 4,415 Lab equipment 12,873 11,772 Office equipment 2,762 2,713 Leasehold improvements 21,723 21,640 Construction in progress 1,555 1,082 Property and equipment, gross 61,938 58,397 Less: accumulated depreciation (24,594) (19,896)Property and equipment, net$37,344 $38,501 For the years ended December 31, 2015, 2014 and 2013, depreciation expense totaled $4.7 million, $3.2 million and $0.8 million, respectively. 8. ACCRUED EXPENSESThe following table summarizes the Company’s accrued expenses for each of the periods indicated: As ofDecember 31,2015 As ofDecember 31,2014 (in thousands) Accrued clinical and preclinical costs $9,587 $3,471 Accrued employee compensation costs 8,189 6,170 Accrued contract manufacturing costs 4,830 3,271 Accrued professional fees 4,258 3,403 Accrued research costs 629 311 Accrued facility-related costs 127 300 Other 1,433 440 Total accrued expenses $29,053 $17,366 9. INDEBTEDNESSSenior Secured Term LoanOn June 26, 2015, the Company entered into a credit and security agreement (the “Credit Agreement”) with MidCap Financial that provides a seniorsecured term loan of $20.0 million. The principal amount may be increased by an additional $20.0 million, for an aggregate amount not to exceed $40.0million. Obligations under the Credit Agreement are secured by substantially all of the Company’s assets, excluding, without limitation, the Company’sintellectual property, certain equity interests relating to foreign subsidiaries and all assets owned by foreign subsidiaries, among others.Borrowings under the Credit Agreement bear interest at a rate per annum equal to 7.75%, with only interest payments due through June 30, 2016. Inaddition to paying interest on the outstanding principal under the Credit Agreement, the Company will pay an origination fee equal to 0.50% of the amountof the term loan when advanced under the Credit Agreement, as well as a final payment fee equal to 2.00% of the amount borrowed under the CreditAgreement when the term loan is fully repaid. Commencing on July 1, 2016 and continuing for the remaining twenty-four months of the facility, theCompany will be required to make monthly principal payments of approximately $0.8 million, or $1.7 million if the facility is increased by the additional$20.0 million referenced above.The Company may voluntarily prepay outstanding loans under the Credit Agreement at any time, provided that the amount is not less than the total ofall of the credit extensions and other related obligations under the Credit Agreement then outstanding. In the event of a voluntary prepayment, the Companyis obligated to pay a prepayment fee equal to 2.95% of the outstanding principal ofF-14such advance if the prepayment is made within twelve months after the closing date, or 2.00% of the outstanding principal of such advance if the prepaymentis made on or after the date that is twelve months after the closing date.The Credit Agreement contains affirmative covenants that include government compliance, reporting requirements, maintaining property, making taxpayments, maintaining insurance and cooperating during litigation. Additionally, the Company is required to maintain a minimum cash balance as collateralwithin its operating bank account with cash and cash equivalents of no less than the greater of the outstanding principal amount or $15.0 million. Negativecovenants include restrictions on asset dispositions, acquisitions, indebtedness, liens, dividends and share purchases, amendments to material contracts andother restrictions.The Credit Agreement includes customary events of default, including cross defaults, a change of control and a material adverse change. Additionally,the Company's failure to be compliant with the affirmative or negative covenants or make payments when they become due will result in an event of default.In connection with the senior secured term loan, the Company recorded $20.0 million as long-term debt in the consolidated balance sheets as ofDecember 31, 2015. In addition, the Company incurred approximately $0.8 million in debt issuance costs that were recorded as a direct deduction to thecarrying value of the term loan in the consolidated balance sheets. These costs are being amortized to interest expense using the effective interest methodover the term of the loan. The following table summarizes the components of the long-term debt recorded for the period indicated: As ofDecember 31, 2015(in thousands) Principal amount$20,000 Unamortized debt issuance costs (570)Net carrying value of senior secured term loan 19,430Long-term Mortgage LoansThe Company has two loans outstanding which bear interest at 4.75%, mature in February 2027 and are collateralized by the facility the Companyowns in Corvallis, Oregon. At December 31, 2015, these loans had unpaid principal balances of $1.0 million and $0.6 million, for a total indebtedness of $1.6million.As of December 31, 2015, the Company recorded approximately $5.9 million as current portion of long-term debt and approximately $15.0 million aslong-term debt on the consolidated balance sheets related to the senior secured term loan and the long-term mortgage loans. Notes payableIn connection with the acquisition of the Andover, Massachusetts facility in May 2014, the Company issued a promissory note with a principalamount of $5.0 million. The interest on the outstanding balance of the promissory note is calculated at the lowest short-term applicable federal rate perannum. The first $2.5 million installment along with the accrued interest was paid on July 15, 2015 and the second $2.5 million installment along with theaccrued interest was paid in January 2016. As of December 31, 2015, the Company recorded approximately $2.5 million as current portion of notes payableon the consolidated balance sheets.For the three years ended December 31, 2015, 2014 and 2013 , the Company incurred interest expenses of approximately $1.4 million, $0.2 millionand $0.1 million, respectively, related to the senior secured term loan, the two mortgage loans and the promissory note.The following table summarizes the total payments under the Company’s debt arrangements: Senior SecuredTerm Loan (1) Long-termMortgage Loans (1) NotesPayable (1) Total (in thousands) 2016$6,494 $171 $2,504 $9,169 2017 10,818 171 — 10,989 2018 5,114 172 — 5,286 2019 — 171 — 171 2020 — 172 — 172 Thereafter — 1,051 — 1,051 Total Payments$22,426 $1,908 $2,504 $26,838F-15 (1)Interest is included 10. EQUITY FINANCINGIn January 2013, the Company sold approximately 87,000 shares of common stock through an At-the-Market (“ATM”) offering which was initiated in2012 (“2012 ATM offering”). The sales in January 2013 generated $2.1 million in net proceeds and fully exhausted the sales of stock available under the2012 ATM sales agreement.In July 2013, the Company entered into an ATM offering (“2013 ATM”) allowing the Company to sell, at its option, up to an aggregate of $125.0million of shares of common stock at market prices. Through September 30, 2013, the Company sold approximately 3.4 million shares under the 2013 ATM,generating $123.0 million in net proceeds and completed the sales of common stock available under the arrangement.In April 2014, the Company sold approximately 2.7 million shares of common stock at an offering price of $38.00 per share. The Company receivedaggregate net proceeds of approximately $94.5 million, after deducting the underwriting discounts and offering related transaction costs.In October 2015, the Company sold approximately 3.3 million shares of common stock at an offering price of $39.00 per share. The Companyreceived aggregate net proceeds of approximately $119.9 million, after deducting the underwriting discounts and offering related transaction costs. 11. STOCK-BASED COMPENSATIONIn June 2011, the Company’s stockholders approved the 2011 Equity Incentive Plan (“2011 Plan”). The 2011 Plan, which authorized 13.0 millionshares of common stock to be issued, allows for the grant of stock options, SARs, RSAs, RSUs, performance shares and performance units. In June 2015,shareholders authorized the issuance of additional 1.7 million shares of common stock under the 2011 Plan. As of December 31, 2015, 1.8 million shares ofcommon stock remain available for future grant under the 2011 Plan.In June 2013, the Company’s stockholders approved the 2013 ESPP with approximately 0.3 million shares of common stock available to be issued. Asof December 31, 2015, 0.1 million shares of common stock remain available for future grant under the 2013 ESPP.In September 2014, the Company initiated the 2014 Employment Commencement Incentive Plan (“2014 Plan”) with approximately 0.6 million sharesof common stock available to be issued. In October 2015, the 2014 Plan was increased by 1.0 million shares of common stock available to be issued. As ofDecember 31, 2015, 1.0 million shares of common stock remain available for future grant under the 2014 Plan.Stock OptionsIn general, stock options have a ten year term and vest over a four year period, with one-fourth of the underlying shares vesting on the first anniversaryof the grant and 1/48th of the underlying shares vesting monthly thereafter, such that the underlying shares will be fully vested on the fourth anniversary ofthe grant, subject to the terms of the applicable plan under which they were granted.The fair values of stock options granted during the periods presented were measured on the date of grant using the Black-Scholes-Merton option-pricing model, with the following assumptions: For the Year Ended December 31, 2015 2014 2013Risk-free interest rate (1) 1.1 – 1.7% 1.4 – 1.7 % 0.7 – 1.7 %Expected dividend yield (2) — — —Expected lives (3) 4.7 – 5.0 years 4.7 – 4.9 years 4.8 – 5.0 yearsExpected volatility (4) 94.3 – 111.1 % 93.0 – 103.0 % 80.0 – 90.7 % (1)The risk-free interest rate is estimated using an average of Treasury bill interest rates over a historical period commensurate with the expected term ofthe option that correlates to the prevailing interest rates at the time of grant.F-16(2)The expected dividend yield is zero as the Company has not paid any dividends to date and does not expect to pay dividends in the future.(3)The expected lives are estimated using historical exercise behavior.(4)The expected volatility is estimated using a blend of calculated volatility of the Company’s common stock over a historical period and impliedvolatility in exchange-traded options of the Company’s common stock.The amounts estimated according to the Black-Scholes-Merton option-pricing model may not be indicative of the actual values realized upon theexercise of these options by the holders.Additionally, the Company is required to estimate potential forfeiture of stock grants and adjust stock-based compensation cost recorded accordingly.The estimate of forfeitures is adjusted over the requisite service period to the extent that actual forfeitures differ, or are expected to differ, from such estimates.Changes in estimated forfeitures are recognized through a cumulative catch-up in the period of change and impact the amount of stock compensationexpense to be recognized in future periods.The following tables summarize the Company’s stock option activity for each of the periods indicated: For the Year Ended December 31, 2015 2014 2013 Weighted Weighted Weighted Average Average Average Exercise Exercise Exercise Shares Price Shares Price Shares Price Grants outstanding at beginning of the period 5,216,203 $24.45 4,190,367 $23.46 2,522,522 $11.76 Granted 2,830,078 20.28 1,694,560 25.67 2,283,719 34.18 Exercised (816,696) 12.26 (86,007) 11.40 (241,056) 11.31 Canceled or expired (713,609) 26.78 (582,717) 22.79 (371,818) 16.83 Grants outstanding at end of the period 6,515,976 $23.91 5,216,203 $24.45 4,190,367 $23.46 Grants exercisable at end of the period 2,617,167 $23.85 2,019,514 $18.69 1,051,329 $11.91 Grants vested and expected to vest at end of theperiod 5,908,213 $23.94 4,462,100 $23.27 3,467,069 $21.50 The weighted-average fair value per share of stock options granted during the years ended December 31, 2015, 2014 and 2013 was $14.98, $18.59 and$22.86, respectively. Weighted Aggregate Average Intrinsic Remaining Value Contractual (in thousands) Life (Years) Options outstanding at December 31, 2015 $96,102 7.16 Options exercisable at December 31, 2015 $38,916 5.60 Options vested and expected to vest at December 31, 2015 $87,029 7.16 The following table summarizes the Company’s stock options vested and exercised for each of the periods indicated: For the Year Ended December 31, 2015 2014 2013 (in thousands) Aggregate grant date fair value of stock options vested $27,858 $17,672 $4,872 Aggregate intrinsic value of stock options exercised $18,138 $1,497 $5,444 F-17Stock Options with Service- and Performance-based ConditionsIn June 2013, the Company granted to executives approximately 0.4 million stock options with service- and performance-based conditions. Vesting isachieved based upon various regulatory filings including NDA for eteplirsen and investigational new drug (“IND”) submissions for other drug candidates andcontinuing service over a four-year period. Through the submission of two IND applications during 2014, 30% of performance awards were triggered to beeligible to vest subject to the remaining service conditions of the awards. No other milestones were achieved during 2015. For the years ended December 31,2015 and 2014, the Company has recognized approximately $0.5 million and $1.2 million in stock-based compensation expense related to the options withperformance-based criteria, respectively.As of December 31, 2015, the total stock-based compensation expense related to non-vested awards with only service-vesting conditions not yetrecognized is approximately $45.5 million and those with service- and performance-based conditions approximates $4.0 million.Restricted Stock AwardsThe Company grants RSAs to members of its board of directors and certain employees. The following table summarizes the Company’s RSA activityfor each of the periods indicated: For the Year Ended December 31, 2015 2014 2013 Weighted Weighted Weighted Average Average Average Exercise Exercise Exercise Shares Price Shares Price Shares Price Grants outstanding at beginning of the period 6,000 $34.92 6,000 $34.92 4,998 $10.08 Granted 181,783 20.80 — — 6,000 34.92 Exercised (24,463) 20.21 — — (4,998) 10.08 Canceled or expired (2,000) 13.90 — — — — Grants outstanding at end of the period 161,320 $21.50 6,000 $34.92 6,000 $34.92 In September 2015, the Company granted certain employees 65,000 RSAs with performance conditions. However, based on the current conditions, theCompany does not expect these awards to vest.Stock Appreciation RightsThe Company issues SARs to employees on the same terms as options granted to employees. The grant date fair value of the SARs is determined usingthe same valuation assumptions as for stock options described above. Stock-based compensation expense is recognized on a straight-line basis over thevesting period of the SARs.In August 2012, 70,000 SARs were granted to the Company’s former President and CEO and have an exercise price of $10.08 per share. In November2012, 100,000 SARs were granted to the Company’s Senior Vice-President and CFO and have an exercise price of $23.85 per share. The SARs are classifiedas equity as the agreements require settlement in shares of stock.F-18The following table summarizes the Company’s SAR activity for each of the periods indicated: For the Year Ended December 31, 2015 2014 2013 Weighted Weighted Weighted Average Average Average Exercise Exercise Exercise Shares Price Shares Price Shares Price Grants outstanding at beginning of the period 170,000 $18.18 170,000 $18.18 170,000 $18.18 Grants outstanding at end of the period 170,000 $18.18 170,000 $18.18 170,000 $18.18 Grants exercisable at end of the period 141,249 $17.59 92,916 $17.80 50,416 $17.48 Grants vested and expected to vest at end of the period 167,813 $18.29 170,000 $18.18 170,000 $18.18 Weighted Aggregate Average Intrinsic Remaining Value Contractual (in thousands) Life (Years) SARs outstanding at December 31, 2015 $3,468 4.41 SARs exercisable at December 31, 2015 $2,964 4.16 SARs vested and expected to vest at December 31, 2015 $3,406 4.45 2013 Employee Stock Purchase PlanUnder the Company’s ESPP, participating employees purchase common stock through payroll deductions. The purchase price is equal to 85% of thelower of the closing price of the Company’s common stock on the first business day and the last business day of the relevant purchase period. The 24-monthaward period will end on August 31, 2017. The following table summarizes the Company’s ESPP activity and expense for each of the periods indicated: For the Year Ended December 31, 2015 2014 Number of shares purchased 75,539 46,290 Proceeds received (in millions) 0.9 1.0 Stock-based Compensation ExpenseFor the years ended December 31, 2015, 2014 and 2013, total stock-based compensation expense was $32.1 million, $20.3 million and $11.1 million,respectively. Included in the amount for the year ended December 31, 2015 is $8.6 million of stock-based compensation expense incurred in connection withthe resignation of the Company’s former CEO. The following table summarizes stock-based compensation expense by function included within theconsolidated statements of operations and comprehensive loss: For the Year Ended December 31, 2015 2014 2013 (in thousands) Research and development $10,403 $8,269 $3,888 General and administrative 21,714 12,076 7,239 Total stock-based compensation $32,117 $20,345 $11,127 The following table summarizes stock-based compensation expense by grant type included within the consolidated statements of operations andcomprehensive loss:F-19 For the Year Ended December 31, 2015 2014 2013 (in thousands) Stock options $29,014 $18,388 $9,632 Restricted stock awards 446 204 149 Restricted stock units — 1 269 Stock appreciation rights 492 587 593 Employee stock purchase plan 2,165 1,165 484 Total stock-based compensation $32,117 $20,345 $11,127 12. 401 (K) PLANThe Company sponsors a 401 (k) Plan (“the Plan”) which is a defined contribution plan. It is available to all employees who are age 21 or older.Participants may make voluntary contributions and the Company makes matching contributions according to the Plan’s matching formula. All matchingcontributions fully vest after one year of service. The expense related to the Plan primarily consists of the Company’s matching contributions.Expense related to the Plan totaled $0.9 million, $0.6 million and $0.4 million for the years ended December 31, 2015, 2014 and 2013, respectively. 13. INCOME TAXESAs of December 31, 2015, the Company had federal and state net operating loss carryforwards of $388.2 million and $313.1 million, respectively,available to reduce future taxable income, which expire between 2016 and 2035. Utilization of these net operating losses could be limited under Section 382of the Internal Revenue Code and similar state laws based on ownership changes and the value of the Company’s stock. Additionally, the Company has$26.1 million and $7.2 million of federal and state research and development credits, respectively, available to offset future taxable income. These federaland state research and development credits begin to expire between 2018 and 2035 and between 2016 and 2030, respectively. Approximately $23.8 millionof the Company’s carryforwards were generated as a result of deductions related to exercises of stock options. When utilized, this portion of the Company’scarryforwards, as tax affected, will be accounted for as a direct increase to contributed capital rather than as a reduction of the year’s provision for incometaxes. The principal differences between net operating loss carryforwards for tax purposes and the accumulated deficit result from timing differences related todepreciation, amortization, treatment of research and development costs, limitations on the length of time that net operating losses may be carried forward,and differences in the recognition of stock-based compensation.The Company had gross deferred tax assets of $219.8 million and $165.8 million at December 31, 2015 and 2014, respectively, primarily from U.S.federal and state net operating loss carryforwards, U.S. federal and state research and development tax credit carryforwards, stock-based compensationexpense and intangibles. A valuation allowance was recorded to reduce the net deferred tax assets to zero because it is more likely than not that the deferredtax assets will not be realized.An analysis of the deferred tax assets is as follows: As of December 31, 2015 2014 (in thousands) Net operating loss carryforwards$138,786 $115,699 Difference in depreciation and amortization 2,694 2,800 Research and development tax credits 31,397 29,127 Stock-based compensation 20,774 13,637 Deferred rent 2,771 2,864 Deferred revenue 1,324 1,213 Capitalized inventory 19,018 — Other 3,060 413 Gross deferred tax assets 219,824 165,753 Valuation allowance (219,824) (165,753)Net deferred tax assets$— $—F-20 The net change in the valuation allowance for deferred tax assets was an increase of $54.1 million and $32.2 million for the years ended December 31,2015 and 2014, respectively, mainly due to the increase in the net operating loss carryforwards, stock-based compensation and research and development taxcredits.The reconciliation between the Company’s effective tax rate and the income tax rate is as follows: For the Year Ended December 31, 2015 2014 2013 Federal income tax rate 34.0 % 34.0 % 34.0 %Research and development tax credits 0.3 2.4 1.4 Valuation allowance (19.1) (21.6) (12.4) Permanent Differences (1.7) (2.4) (8.8) Foreign rate differential (13.5) (12.4) (14.2) Effective tax rate — % — % — % Permanent differences affecting the Company’s effective tax rate include loss on changes in warrant valuation and losses in a foreign jurisdiction. Allwarrants issued in January and August 2009 were exercised or expired during 2014. As a result, the Company did not incur loss on changes in warrantvaluation for the year ended December 31, 2015. On December 31, 2012, the Company licensed certain intellectual property of Sarepta Therapeutics, Inc. toits wholly owned subsidiary, Sarepta International C.V. The parties also entered into a contract research agreement under which Sarepta Therapeutics, Inc.performs research services for Sarepta International C.V. For the years ended December 31, 2015 and 2014, Sarepta International C.V. incurred costs of $87.4million and $48.5 million, respectively, in connection with the research and development activities.The reconciliation of the beginning and ending amount of total unrecognized tax benefits for the years ended December 31, 2015, 2014 and 2013 areas follows: For the Year Ended December 31, 2015 2014 2013 (in thousands) Balance at beginning of the period$— $— $— Increase related to current year tax positions 613 — — Increase related to prior year tax positions 3,093 — — Balance at end of the period$3,706 $— $—The balance of total unrecognized tax benefits at December 31, 2015, if recognized, would not affect the effective tax rate on income from continuingoperations, due to a full valuation allowance against the Company’s deferred tax assets. The Company does not expect that the amount of unrecognized taxbenefits to change materially in the next twelve months. The Company, including its domestic subsidiaries, files consolidated U.S. federal and state incometax returns. The Company’s policy is to recognize interest and/or penalties related to income tax matters in income tax expense. The Company had no accrualfor interest or penalties on its balance sheet at December 31, 2015 or December 31, 2014 and has not recognized interest and/or penalties in the statement ofoperations for years ended December 31, 2015, 2014 or 2013. 14. NET LOSS PER SHAREBasic net loss per share is computed by dividing net loss by the weighted-average number of shares of common stock outstanding. Diluted net loss pershare is computed by dividing net loss by the weighted-average number of shares of common stock and dilutive common stock equivalents outstanding.Given that the Company recorded a net loss for each of the periods presented, there is no difference between basic and diluted net loss per share since theeffect of common stock equivalents would be anti-dilutive and are, therefore, excluded from the diluted net loss per share calculation. F-21 For the Year Ended December 31, 2015 2014 2013 (in thousands, except per share amounts) Net loss (220,030) $(135,789) $(111,985)Weighted-average number of shares of common stock and common stock equivalents outstanding: Weighted-average number of shares of common stock outstanding for computing basic loss per share 42,290 40,026 33,850 Dilutive effect of outstanding stock awards and stock options after application of the treasury stock method* — — — Weighted-average number of shares of common stock and dilutive common stock equivalents outstanding for computing diluted loss per share 42,290 40,026 33,850 Net loss per share — basic and diluted $(5.20) $(3.39) $(3.31) *For the year ended December 31, 2015 and 2014, stock options, RSAs and SARs to purchase approximately 6.8 million and 5.4 million shares ofcommon stock, respectively, were excluded from the net loss per share calculation as their effect would have been anti-dilutive. For the year ended 2013, stock options, RSAs, RSUs, SARs and warrants to purchase approximately 5.2 million shares of common stock were excludedfrom the net loss per share calculation as their effect would have been anti-dilutive. 15. COMMITMENTS AND CONTINGENCIESLease ObligationsIn June 2013, the Company entered into a lease agreement (“Cambridge lease”) for its headquarters located in Cambridge, Massachusetts. As ofDecember 31, 2015, the Company had entered into five amendments to the Cambridge lease, increasing its total rental space for its headquarters to 77,390square feet. The Cambridge lease and its amendments will expire in January 2021. The agreement calls for a security deposit in the form of a letter of credittotaling $0.6 million. The Company purchased a certificate of deposit (“CD”) to meet the requirement and it was recorded as a long-term restrictedinvestment in the consolidated balance sheets as of December 31, 2015.In June 2014, the Company entered into an agreement to sublease from an unrelated third party 10,939 square feet of office space. The sublease willexpire in February 2021.In January 2014, the Company entered into an agreement to sublease 15,077 square feet of office space to an unrelated third party. The subleaseexpired in July 2015. In August 2015, the Company entered into an agreement to sublease this space to another unrelated third party. The sublease willexpire in September 2017.In February 2015, the Company entered into an agreement to sublease 7,461 square feet of office space to an unrelated third party. The sublease willexpire in February 2016.The Company also leases laboratory and office space in Corvallis, Oregon which will expire in December 2020.The following table summarizes the aggregate non-cancelable future minimum payments under the Company’s leases: As ofDecember 31, 2015(in thousands) 2016 $4,616 2017 4,733 2018 4,851 2019 4,971 2020 5,093 Thereafter 540 Total minimum lease payments $24,804F-22 Royalty ObligationsThe Company is also obligated to pay royalties upon the net sales of its products. The royalty rates are in the low to mid-single-digit percentages forboth inside and outside the United States. For example, under the Amended and Restated License Agreement with UWA signed in April 2013, the Companyis obligated to pay a low-single-digit percentage of royalty on the net sales of products covered by issued patents, which include eteplirsen.Milestone ObligationsThe Company has license agreements for which it is obligated to pay development and commercial milestones as a product candidate proceeds fromthe submission of an IND application through approval for commercial sale. For the year ended December 31, 2015, the Company recognized approximately$0.2 million relating to certain milestone payments under these agreements. There were no significant milestone payments under these agreements for theyears ended December 31, 2014 or 2013.In April 2013, the Company and UWA entered into an agreement under which an existing exclusive license agreement between the Company andUWA was amended and restated. Under the terms of this agreement, UWA granted the Company an exclusive license to certain UWA intellectual propertyrights in exchange for up to $7.1 million in up-front, development and commercial milestone payments. Under the Amended and Restated UWA LicenseAgreement, the Company also has the option to purchase future royalties upfront. Under this option, the Company may be required to make to the UWA anup-front payment of $30.0 million as well as $20.0 million in aggregate contingency payment upon successful achievement of certain commercialmilestones. For the years ended December 31, 2015, 2014 and 2013, the Company recorded $0.2 million, $0.0 million and $1.0 million, respectively, relatingto certain up-front and development milestone payments required under the agreement as research and development expense in the consolidated statementsof operations and comprehensive loss.Additionally, the Company has entered into various collaboration and license agreements with third party entities. Under these agreements, theCompany may be required to make payments up to $39.2 million in the aggregate related to certain development, regulatory and commercial milestones. Forthe year ended December 31, 2015, the Company has not made and is not under any current obligation to make any such milestone payments, as theconditions triggering any such milestone payment obligations have not been satisfied. LitigationIn the normal course of business, the Company may from time to time be named as a party to various legal claims, actions and complaints, includingmatters involving securities, employment, intellectual property, effects from the use of therapeutics utilizing its technology, or others. For example, purportedclass action complaints were filed against the Company and certain of its officers in the U.S. District Court for the District of Massachusetts on January 27,2014 and January 29, 2014. The complaints were consolidated into a single action (Corban v. Sarepta, et. al., No. 14-cv-10201) by order of the court on June23, 2014, and plaintiffs were afforded 28 days to file a consolidated amended complaint. The plaintiffs’ consolidated amended complaint, filed on July 21,2014, sought to bring claims on behalf of themselves and persons or entities that purchased or acquired securities of the Company between July 10, 2013 andNovember 11, 2013. The consolidated amended complaint alleged that Sarepta and certain of its officers violated the federal securities laws in connectionwith disclosures related to eteplirsen, the Company’s lead therapeutic candidate for DMD, and seeks damages in an unspecified amount. Pursuant to thecourt’s June 23, 2014 order, Sarepta filed a motion to dismiss the consolidated amended complaint on August 18, 2014, and argument on the motion washeld on March 12, 2015. On March 31, 2015, the Court dismissed plaintiffs’ amended complaint. On April 30, 2015, plaintiffs in the Corban suit filed amotion for leave seeking to file a further amended complaint, which the Company opposed. Following a hearing on August 12, 2015, the Court denied thismotion, and on September 22, 2015, the Court dismissed the case. The plaintiffs filed a Notice of Appeal in the Court of Appeals for the First Circuit onSeptember 29, 2015. On January 27, 2016, the plaintiffs filed a motion to vacate the District Court’s order denying leave to amend and dismissing the case.The Company filed its opposition with the District Court on February 11, 2016, and oral argument on the plaintiffs’ motion is scheduled for February 25,2016. The plaintiffs’ appellate brief is due to the First Circuit on March 22, 2016. An estimate of the possible loss or range of loss cannot be made at thistime.Another complaint was filed in the U.S. District Court for the District of Massachusetts on December 3, 2014 by William Kader, Individually and onBehalf of All Others Similarly Situated v. Sarepta Therapeutics Inc., Christopher Garabedian, and Sandesh Mahatme (Kader v. Sarepta et.al 1:14-cv-14318),asserting violations of Section 10(b) of the Exchange Act and Securities and Exchange Commission Rule 10b-5 against the Company, ChristopherGarabedian and Sandesh Mahatme. Plaintiffs’ amended complaint, filed on March 20, 2015, alleges that the defendants made material misrepresentations oromissions during the putative class period of April 21, 2014 through October 27, 2014, regarding the sufficiency of the Company’s data for submission of anNDA for eteplirsen and the likelihood of the FDA accepting the NDA based on that data. Plaintiffs seek compensatory damages and fees. The Companyreceived service of the complaint on January 5, 2015. Sarepta filed a motion to dismiss the complaint on May 11, 2015,F-23pursuant to the scheduling order entered on February 20, 2015, which plaintiffs have opposed. Oral argument on the motion has been scheduled for March 2,2016. An estimate of the possible loss or range of loss cannot be made at this time.In addition, two derivative suits were filed based upon the Company’s disclosures related to eteplirsen. On February 5, 2015, a derivative suit was filedagainst the Company’s Board of Directors in the 215th Judicial District of Harris County, Texas (David Smith, derivatively on behalf of Sarepta Therapeutics,Inc., v. Christopher Garabedian et. al, Cause No. 2015-06645). The claims allege that Sarepta’s directors caused Sarepta to disseminate materially false and/ormisleading statements in connection with disclosures concerning the Company’s submission of the NDA for eteplirsen. Plaintiff seeks unspecifiedcompensatory damages, actions to reform and improve corporate governance and internal procedures, disgorgement of profits, benefits and othercompensation obtained by the directors, and attorneys’ fees. On March 24, 2015, the parties agreed to abate the case pending the resolution of both suitspending in federal court in the District of Massachusetts, Corban and Kader. Additionally, on February 24, 2015, a derivative suit was filed against theCompany’s Board of Directors with the Court of Chancery of the State of Delaware (Ira Gaines, and the Ira J. Gaines Revocable Trust U/A, on behalf ofnominal defendant Sarepta Therapeutics, Inc., vs. Goolsbee et. al., No. 10713). The claims allege that the defendants participated in making materialmisrepresentations or omissions during the period of April 21, 2014 through October 27, 2014, regarding the sufficiency of the Company’s data forsubmission of the NDA for eteplirsen and the likelihood of the FDA accepting the NDA based on that data. Plaintiffs seek unspecified compensatorydamages, punitive damages, actions to reform and improve corporate governance and internal procedures, and attorneys’ fees. On March 26, 2015, the partiesagreed to stay the case pending the resolution of Kader, pending in federal court in the District of Massachusetts. An estimate of the possible loss or range ofloss cannot be made at this time.Additionally, on September 23, 2014, a derivative suit was filed against the Company’s Board of Directors with the Court of Chancery of the State ofDelaware (Terry McDonald, derivatively on behalf of Sarepta Therapeutics, Inc., et. al vs. Goolsbee et. al., No. 10157). The claims allege, among other things,that (i) the Company’s non-employee directors paid themselves excessive compensation fees for 2013, (ii) that the compensation for the Company’s formerCEO, Christopher Garabedian, was also excessive and such fees were the basis for Mr. Garabedian’s not objecting to or stopping the excessive fees for thenon-employee directors and (iii) that the disclosure in the 2013 proxy statement was deficient. The relief sought, among others, includes disgorgement andrescindment of allegedly excessive or unfair payments and equity grants to Mr. Garabedian and the directors, unspecified damages plus interest, a declarationthat the Company’s Amended and Restated 2011 Equity Plan at the 2013 annual meeting was ineffective and a revote for approved amendments, correctionof misleading disclosures and plaintiff’s attorney fees. The Company has reached an agreement in principle with the parties in the McDonald suit and do notbelieve that disposition of the McDonald suit should have a material financial impact on the Company. An estimate of the possible loss or range of losscannot be made at this time.Purchase CommitmentsThe Company has entered into long-term contractual arrangements from time to time for the provision of goods and services.The following table presents non-cancelable contractual obligations arising from these arrangements: As ofDecember 31, 2015(in thousands) 2016 $60,442 2017 29,664 2018 28,521 2019 11,408 Total purchase commitments $130,035 In connection with an amendment to a supply agreement, in September 2015, the Company issued an irrevocable standby letter of credit totaling$10.7 million to a contract manufacturing vendor. The obligation secured by the letter of credit will be fulfilled upon full payment of all deposits andpurchase payments by the end of 2016. To meet the requirement of the letter of credit, the Company purchased $10.7 million in a certificate of deposit with aSeptember 2016 maturity date. If the commitments have not occurred as of December 31, 2016, the letter of credit will be extended. The Company hasrecorded this $10.7 million as a restricted investment on the consolidated balance sheet as of December 31, 2015. F-2416. FINANCIAL INFORMATION BY QUARTER (UNAUDITED) 2015 for Quarter Ended December 31 September 30 June 30 March 31 (in thousands) Revenue from research contracts and other grants$1,253 $— $— $— Operating expenses: Research and development 41,376 36,673 29,180 39,165 General and administrative 24,329 15,090 12,927 22,697 Total operating expenses 65,705 51,763 42,107 61,862 Operating loss (64,452) (51,763) (42,107) (61,862)Other income (loss): Interest income and other, net (229) (176) 256 303 Total other income (loss) (229) (176) 256 303 Net loss$(64,681) $(51,939) $(41,851) $(61,559) Net loss per share—basic and diluted$(1.44) $(1.25) $(1.01) $(1.49)Shares used in per share calculations—basic and diluted 44,882 41,565 41,357 41,324 2014 for Quarter Ended December 31 September 30 June 30 March 31 (in thousands) Revenue from research contracts and other grants$27 $1,059 $2,583 $6,088 Operating expenses: Research and development 30,832 21,852 20,641 20,906 General and administrative 13,917 12,882 12,213 10,303 Total operating expenses 44,749 34,734 32,854 31,209 Operating loss (44,722) (33,675) (30,271) (25,121)Other income (loss): Interest income and other, net 306 193 181 99 Gain (loss) on change in warrant valuation — 4,256 (3,784) (3,251)Total other income (loss) 306 4,449 (3,603) (3,152)Net loss$(44,416) $(29,226) $(33,874) $(28,273) Net loss per share—basic and diluted$(1.08) $(0.71) $(0.85) $(0.75)Shares used in per share calculations—basic and diluted 41,304 41,066 39,862 37,821 F-25Exhibit 21.1Sarepta Therapeutics, Inc.Subsidiaries of the Registrant Name Jurisdiction of IncorporationST International Holdings, Inc. Delaware, USASTIH Two, Inc. Delaware, USASarepta Securities Corp. Massachusetts, USASarepta International CV NetherlandsAVI BioPharma International Limited United Kingdom Exhibit 23.1Consent of Independent Registered Public Accounting FirmThe Board of DirectorsSarepta Therapeutics, Inc.: We consent to the incorporation by reference in the registration statements (Nos. 333-160922, 333-150021, 333-138299, 333-133211, 333-109015, 333-86778, 333-105412, 333-68502, 333-45888, 333-93135, 333-86039, 333-180258 and 333-184807) on Form S-3 and (Nos. 333-199037, 333-192287, 333-172823, 333-175031, 333-101826, 333-49996, 333-49994 and 333-34047) on Form S-8 of Sarepta Therapeutics, Inc., and subsidiaries of ourreports dated February 25, 2016, with respect to the consolidated balance sheets of Sarepta Therapeutics, Inc., and subsidiaries as of December 31, 2015 and2014, and the related consolidated statements of operations and comprehensive loss, stockholders’ equity, and cash flows for each of the years in the three-year period ended December 31, 2015, and the effectiveness of internal control over financial reporting as of December 31, 2015, which reports appear in theDecember 31, 2015 annual report on Form 10 K of Sarepta Therapeutics, Inc., and subsidiaries. (signed) KPMG LLP Cambridge, MassachusettsFebruary 25, 2016Exhibit 31.1CERTIFICATIONI, Edward Kaye, MD, certify that:1. I have reviewed this Annual Report on Form 10-K of Sarepta Therapeutics, Inc., (the “Registrant”);2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the Registrant as of, and for, the periods presented in this report;4. The Registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for theRegistrant and have:(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, toensure that material information relating to the Registrant, including its consolidated subsidiaries, is made known to us by others within those entities,particularly during the period in which this report is being prepared;(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposesin accordance with generally accepted accounting principles;(c) Evaluated the effectiveness of the Registrant’s disclosure controls and procedures and presented in this report our conclusions about theeffectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and(d) Disclosed in this report any change in the Registrant’s internal control over financial reporting that occurred during the Registrant’s most recentfiscal quarter (the Registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, theRegistrant’s internal control over financial reporting; and5. The Registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theRegistrant’s auditors and the audit committee of the Registrant’s board of directors (or persons performing the equivalent functions):(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonablylikely to adversely affect the Registrant’s ability to record, process, summarize and report financial information; and(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the Registrant’s internal controlover financial reporting. February 25, 2016 /s/ Edward Kaye, MD Edward Kaye, MD Interim Chief Executive Officer, Senior Vice President, ChiefMedical Officer (Principal Executive Officer) EXHIBIT 31.2CERTIFICATIONI, Sandesh Mahatme, certify that:1. I have reviewed this Annual Report on Form 10-K of Sarepta Therapeutics, Inc., (the “Registrant”);2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the Registrant as of, and for, the periods presented in this report;4. The Registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for theRegistrant and have:(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, toensure that material information relating to the Registrant, including its consolidated subsidiaries, is made known to us by others within those entities,particularly during the period in which this report is being prepared;(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposesin accordance with generally accepted accounting principles;(c) Evaluated the effectiveness of the Registrant’s disclosure controls and procedures and presented in this report our conclusions about theeffectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and(d) Disclosed in this report any change in the Registrant’s internal control over financial reporting that occurred during the Registrant’s most recentfiscal quarter (the Registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, theRegistrant’s internal control over financial reporting; and5. The Registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theRegistrant’s auditors and the audit committee of the Registrant’s board of directors (or persons performing the equivalent functions):(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonablylikely to adversely affect the Registrant’s ability to record, process, summarize and report financial information; and(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the Registrant’s internal controlover financial reporting. February 25, 2016 /s/ Sandesh Mahatme Sandesh Mahatme Senior Vice President, Chief Financial Officer (Principal Financial and Accounting Officer) EXHIBIT 32.1CERTIFICATION PURSUANT TOSECTION 906 OF THE SARBANES-OXLEY ACT OF 2002(18 U.S.C. SECTION 1350)I, Edward Kaye, MD, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that theAnnual Report of Sarepta Therapeutics, Inc. on Form 10-K for the fiscal year ended December 31, 2015, fully complies with the requirements of Section 13(a)or 15(d) of the Securities Exchange Act of 1934 and that information contained in such Annual Report on Form 10-K fairly presents, in all material respects,the financial condition and results of operations of Sarepta Therapeutics, Inc. February 25, 2016 /s/ Edward Kaye, MD Edward Kaye, MD Interim Chief Executive Officer, Senior Vice President, ChiefMedical Officer (Principal Executive Officer) A signed original of this written statement required by Section 906 of the Sarbanes-Oxley Act of 2002 has been provided to Sarepta Therapeutics, Inc.and will be retained by Sarepta Therapeutics, Inc. and furnished to the Securities and Exchange Commission or its staff upon request.This certification accompanies this Report on Form 10-K pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 and shall not, except to theextent required by such Act, be deemed filed by Sarepta Therapeutics, Inc. for purposes of Section 18 of the Securities Exchange Act of 1934, as amended(the “Exchange Act”). Such certification will not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, orthe Exchange Act, except to the extent that Sarepta Therapeutics, Inc. specifically incorporates it by reference. Exhibit 32.2CERTIFICATION PURSUANT TOSECTION 906 OF THE SARBANES-OXLEY ACT OF 2002(18 U.S.C. SECTION 1350)I, Sandesh Mahatme, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that theAnnual Report of Sarepta Therapeutics, Inc. on Form 10-K for the fiscal year ended December 31, 2015, fully complies with the requirements of Section 13(a)or 15(d) of the Securities Exchange Act of 1934 and that information contained in such Annual Report on Form 10-K fairly presents, in all material respects,the financial condition and results of operations of Sarepta Therapeutics, Inc. February 25, 2016 /s/ Sandesh Mahatme Sandesh Mahatme, Senior Vice President, Chief Financial Officer (Principal Financial and Accounting Officer) A signed original of this written statement required by Section 906 of the Sarbanes-Oxley Act of 2002 has been provided to Sarepta Therapeutics, Inc.and will be retained by Sarepta Therapeutics, Inc. and furnished to the Securities and Exchange Commission or its staff upon request.This certification accompanies this Report on Form 10-K pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 and shall not, except to theextent required by such Act, be deemed filed by Sarepta Therapeutics, Inc. for purposes of Section 18 of the Securities Exchange Act of 1934, as amended(the “Exchange Act”). Such certification will not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, orthe Exchange Act, except to the extent that Sarepta Therapeutics, Inc. specifically incorporates it by reference. 

Continue reading text version or see original annual report in PDF format above