Summary of Sarepta Therapeutics (SRPT) Conference Call - July 18, 2025 Company Overview - **Company**: Sarepta Therapeutics (SRPT) - **Focus**: Gene therapy for Limb Girdle Muscular Dystrophy (LGMD) and related conditions Key Points Industry and Company Context - The call addressed recent developments in the LGMD program, particularly concerning the investigational candidate SRP-9004 for LGMD type 2D [3][4] - The company is transitioning focus from gene therapy to its siRNA platform due to risk-adjusted net present values (NPVs) and the need to manage expenses [4][10] Core Issues Discussed - A serious adverse event (fatality) occurred in a trial for SRP-9004, which was not deemed material to the overall discussions on the previous call [3][4] - The decision to discontinue other LGMD programs was based on risk-adjusted NPVs rather than safety events [10][18] - The company has paused dosing of Elevitus in non-ambulatory patients while developing a protocol for sirolimus as prophylactic immunosuppression [5][51] Safety and Regulatory Considerations - The event in question involved a 51-year-old non-ambulatory patient and was reported to the FDA, which has not changed its position regarding Elevitus [6][21][94] - The company maintains that the risk of acute liver failure (ALI) is a known risk associated with AAV-mediated therapies, particularly in non-ambulatory patients [52][83] - Approximately 30-40% of patients experience elevated liver enzymes, with a subset requiring hospitalization [47][88] Patient Population and Clinical Trials - Between 35 and 40 patients have been dosed across LGMD trials, with a roughly equal split between ambulatory and non-ambulatory patients [56] - The company has conducted three clinical trials for LGMD2E, with no fatalities reported in other gene therapy trials [32][41] Future Directions and Market Considerations - The company plans to continue pursuing the LGMD2E program (SRP-9003) despite the challenges, as it is an ultra-rare disease with significant unmet needs [60] - Discussions with the FDA regarding the use of sirolimus and its potential impact on the label for SRP-9003 are ongoing [41][51] Communication and Transparency - The company emphasizes its commitment to transparency with investors, patients, and physicians regarding safety signals and clinical trial results [18][100] - Ongoing communication with the physician community about the risks associated with Elevitus and LGMD therapies is prioritized [98] Additional Important Points - The company has a history of being transparent about safety signals and has communicated the risks of elevated liver enzymes to the physician community [18][98] - The manufacturing processes for different therapies (e.g., Elevitus vs. LGMD) are distinct, which may influence safety profiles [32][29] - The company is evaluating the potential need for additional data to support the Biologics License Application (BLA) for LGMD2E [41][68] This summary captures the essential points discussed during the conference call, focusing on the company's strategic direction, safety considerations, and ongoing communication efforts.

Financial Data and Key Metrics Changes - The company reported a solid financial position with $1.6 billion on the balance sheet, indicating strong capital efficiency and the ability to fund future projects [3][4]. Business Line Data and Key Metrics Changes - The approved product, Kasjevi, is now in eight different jurisdictions for treating sickle cell and beta thalassemia, with a revenue of $14 million generated from 90 cells collected and 65 ATCs as of Q1 [12][13][22]. - The company is targeting 75 ATCs to support the demand for Kasjevi, indicating a significant multi-billion dollar market opportunity [14][16]. Market Data and Key Metrics Changes - The company sees a substantial market in the Middle East, with over 23,000 patients identified in Gulf Coast countries, which is expected to play a significant role in Kasjevi's market expansion [16][17]. Company Strategy and Development Direction - The company aims to focus on transformative gene-based medicines while exploring opportunistic deals, such as the partnership with Sirius Therapeutics for an siRNA platform [4][8]. - The strategic approach includes a phase two trial for Factor XI, which is expected to provide immediate value-creating catalysts in the next 12 to 18 months [10][11]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the launch performance of Kasjevi and the potential for significant patient initiation growth, supported by manufacturing investments [13][14][22]. - The company is optimistic about the upcoming data readouts from various programs, including CTX 310, which showed promising early results with an 82% reduction in triglycerides and 81% reduction in LDL [6][28]. Other Important Information - The company is actively looking for business development opportunities in a buyer's market, with plans to explore partnerships that can create significant value [48][50]. - The cost of goods for new therapies is expected to be in the low five-figure range, allowing for competitive pricing against existing therapies [44][45]. Q&A Session Summary Question: What does the Sirius deal do for your platform with siRNAs? - The Sirius deal is seen as a diversification play, allowing the company to explore complementary assets in a buyer's market [8][9]. Question: How has the launch of Kasjevi been trending? - The launch has been successful, with significant revenue and patient initiation growth expected [12][13]. Question: What are the key days to watch for the Factor XI program? - The initiation of the TKA study in the second half of the year is a key milestone [11]. Question: How does the company plan to address the preconditioning regimen for Kasjevi? - The company is working on approaches to make the preconditioning regimen more comfortable for patients [23][25]. Question: What is the company's strategy for broad diseases versus rare diseases? - The company aims to ensure low production costs to remain competitive in both broad and rare disease markets [44][45].