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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 1 Patients can’t wait for the next breakthrough in medical research. So neither willwe. DILLON Living with Duchenne muscular dystrophy Doug Ingram President & CEO Louise Rodino-Klapac, PhD Executive Vice President, Head of R&D, Chief Scientific Officer June 16, 2025 An ELEVIDYS Safety Update in Non-Ambulatory Patients
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 2 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 2 Doug Ingram
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 3 Forward-looking statements This presentation contains “forward-looking statements.” Any statements that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements relating to our future operations and financial guidance, research and development programs, clinical trials, ELEVIDYS, the potential benefits of sirolimus, and expected plans and milestones, including conveying an expert safety panel and engaging with regulators on an enhanced immunosuppressive regimen. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: different methodologies, assumptions and applications we use to assess particular safety or efficacy parameters may yield different statistical results, and even if we believe the data collected from clinical trials are positive, these data may not be sufficient to support approval by the FDA or other global regulatory authorities; success in clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and the results of future research may not be consistent with past positive results or with advisory committee recommendations, or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; our products may not be widely adopted by patients, payors or healthcare providers, which would adversely impact our potential profitability and future business prospects; our products or product candidates may be perceived as insufficiently effective, unsafe or may result in unforeseen adverse events; our products or product candidates may cause undesirable side effects that result in significant negative consequences following any marketing approval; we may not be able to comply with all FDA requests in a timely manner or at all; the possible impact of regulations and regulatory decisions by the FDA and other regulatory agencies on our business; and those risks identified under the heading “Risk Factors” in our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company, which you are encouraged to review. Any of the foregoing risks could materially and adversely affect the Company’s business, results of operations and the trading price of Sarepta’s common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review theSEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained herein. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof, except as required by law.
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 4 Safety update regarding ELEVIDYS for non-ambulatory individuals with Duchenne • New report of liver injury in a non-ambulatory individual with Duchenne who has passed away from acute liver failure (ALF) • Plan to develop an enhanced immunosuppressive regimen in consultation with a panel of multi- disciplinary clinical experts, and regulators o Panel will evaluate data and assess Sarepta's proposed enhanced immunosuppressive regimen, which includes sirolimus • Suspension of commercial shipments of ELEVIDYS for infusions in non-ambulatory patients until enhanced regimen is approved and in place • Pause of ENVISION study while seeking a protocol amendment to incorporate additional immunosuppression
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 5 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 5 Louise Rodino-Klapac, PhD
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 6 Scientific rationale for an immunosuppression regimen with sirolimus • AAV Class Effect – AAV in the liver triggers T cell response and inflammation, causing acute liver failure in severe cases • Enhanced Immunosuppression with Sirolimus Designed to Mitigate Acute Liver Failure Risk – Data support sirolimus effective at inhibiting T cells, mitigating the inflammatory response that can lead to acute liver injury Sirolimus downregulates T cells that react to gene therapy
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 7 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 7 Data support the proposed enhanced regimen
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 8 Preclinical Results: Sirolimus* suppresses AAVrh74 immune response Study Details: • AAVrh74.CMV.eGFP • AAV Dose: 1.33 x 1014 vg/kg • N=3 per group • 90-105 days in life 8 15 29 36 50 64 78 90 96 8 15 29 36 50 64 78 90 96 8 15 29 36 50 64 78 90 96 101 102 103 104 105 106 Anti-AAVrh74 IgG ELISA Time point (days) Titer (1:X) Saline Vector Control Vector + ImmTOR 400 Seroconverted animalsTiter cutoff for positive samples 15 22 36 50 64 78 90 96 15 22 36 50 64 78 90 96 15 22 36 50 64 78 90 96 -50 0 100 150 200 eGFP-specific T-cell immune response Time point (days) IFN-γ SFC / 106 PBMC Saline Vector Control Vector + ImmTOR 50 SFC cutoff for positive samples AAVrh74 Immune Response *ImmTOR (sirolimus encapsulated LNP)
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 9 Saline Vector Control ImmTOR + Vector Key Liver Function Tests 0 50 100 0 200 400 600 800 AST Days U/L 0 50 100 0 200 400 600 ALT Days U/L 0 50 100 0.0 0.1 0.2 0.3 0.4 TBIL Days mg/dL Preclinical Results: Sirolimus* effectively mitigates liver enzyme elevations *ImmTOR (sirolimus encapsulated LNP)
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 10 GFP Expression (IF) Preclinical Results: Confirming gene expression in target tissue Skeletal Muscle Liver Heart 0 100 200 300 400 500 5000 10000 15000 20000 pg GFP/ μg Total Protein Vector Control ImmTOR + Vector GFP Expression (ELISA)
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 11 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 11 Enhanced risk mitigation plan
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 12 Summary of enhanced risk mitigation plan • Non-ambulatory patients – Suspend shipment of ELEVIDYS until alignment with expert panel and regulators on risk mitigation such as enhanced immunosuppression regimen – Commitment to ongoing vigilance and learning • Ambulatory patients – No changes to treatment protocol or patient experience (steroid regimen remains the same) – Ongoing practice of administering corticosteroids before and after ELEVIDYS infusion – Post-treatment monitoring for elevated liver enzymes to continue Clinical setting Commercial setting • Paused dosing in ENVISION study to allow for the evaluation of a protocol amendment • Amendment to introduce sirolimus as part of the immunosuppressive approach
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 13 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 13 Doug Ingram
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©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 14 ©SAREPTA THERAPEUTICS, INC. 2025. ALL RIGHTS RESERVED. 14 Q&A