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 - In Q1 2025, the company achieved total net product revenue of $612 million, representing a 70% growth year-over-year [7][40] - Elevitus sales reached $375 million, marking a 180% increase compared to the same quarter last year [7][40] - The PMO franchise generated $237 million in revenue, up 5% year-over-year [7][40] - Total revenues for Q1 were $745 million, an increase of $331 million or 80% year-over-year [41] Business Line Data and Key Metrics Changes - The PMO franchise revenue grew by 5%, while Elevitus saw a significant increase of 180% [7][40] - The company reported a GAAP operating loss of $448 million and a non-GAAP operating loss of $332 million for Q1 2025 [43][44] - R&D expenses on a GAAP basis were $773 million, a year-over-year increase of $573 million, primarily due to the Arrowhead collaboration [42] Market Data and Key Metrics Changes - The company is revising its net product revenue guidance for 2025 to a range of $2.3 billion to $2.6 billion, reflecting a 37% increase from 2024 at the midpoint [8][44] - The company anticipates Q2 revenue could be as much as 20% lower than Q1 due to various factors including a safety event and administrative delays [19][20] Company Strategy and Development Direction - The company is focused on addressing administrative complexities and enhancing site capacity to improve patient access to Elevitus [22][23] - A comprehensive promotional campaign for Elevitus has been launched to increase awareness and understanding among healthcare providers and patients [23] - The company plans to expand its LGMD portfolio and continue advancing its siRNA platform, with significant data expected to be shared later in the year [30][34] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenging environment in biotech but emphasized the company's strong position due to approved therapies and revenue generation [6][7] - The tragic safety event involving a patient infused with Elevitus has led to a more cautious outlook, but management remains confident in the therapy's overall safety profile [8][9] - Management expects a recovery in demand starting in the summer, with a significant uptick anticipated in the second half of the year [64] Other Important Information - The company has a strong cash position with $647 million in cash and equivalents, and an additional $600 million available through a revolving credit facility [39][44] - The FDA has confirmed receipt of a labeling supplement that includes the recent patient death, with a target review date set for no later than Q4 2025 [78] Q&A Session Summary Question: What has been the biggest driver of potential downside pressure leading to revised guidance? - Management indicated that it is a mix of all three factors: cycle times, administrative processes, and the safety event, with cycle times being the most mechanically impactful [48][49] Question: How does the company plan to direct patients to sites with more capacity? - Management stated that the issue is more about focus rather than the number of sites, emphasizing the need for increased education and outreach to secondary sites [58][59] Question: What percentage of sales does Elevitus represent in the new guidance? - Management confirmed that the revision in total net product revenue was exclusively related to Elevitus, which is the primary driver of the guidance change [66] Question: What are the expectations regarding the potential label update for Elevitus? - Management indicated that a labeling supplement was submitted in April, and the FDA has set a target completion date for the review by Q4 2025 [78] Question: How is the company interacting with the FDA regarding the limb girdle programs? - Management reported that interactions with the FDA have remained positive, with confirmation of the accelerated approval pathway for the limb girdle programs [84]

Financial Data and Key Metrics Changes - In Q1 2025, the company achieved total net product revenue of $612 million, representing a 70% growth year-over-year [6][38] - Elevitus sales reached $375 million, marking a 180% increase compared to the same quarter last year [6][38] - The PMO franchise generated $237 million, up 5% year-over-year [6][38] - The company revised its net product revenue guidance for 2025 to a range of $2.3 billion to $2.6 billion, reflecting a 37% increase from 2024 at the midpoint [7][42] Business Line Data and Key Metrics Changes - The PMO franchise grew by 5%, while Elevitus saw a significant increase of 180% in sales [6][38] - Collaboration and other revenues amounted to $133 million, primarily from Roche [38] Market Data and Key Metrics Changes - The company noted that 60% of current revenue comes from top sites, which are experiencing high demand and long wait times for appointments [12] - The administrative process for gene therapy has become more complex, leading to longer turnaround times for infusions [10][18] Company Strategy and Development Direction - The company is focusing on addressing administrative challenges and enhancing site capacity to improve patient access to Elevitus [19] - A comprehensive promotional campaign for Elevitus was launched to increase awareness and understanding among healthcare providers and patients [20] - The company aims to expand its treatment network by engaging more community sites to alleviate capacity issues at top centers [19] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenges faced in Q1 2025, including a severe flu season and a tragic safety event that impacted patient infusions [5][16] - The company remains optimistic about long-term demand for Elevitus, expecting a recovery in sales starting in the summer [17][64] - Management emphasized the importance of education and communication to address concerns stemming from the recent safety event [52][60] Other Important Information - The company reported a GAAP net loss of $448 million for Q1 2025, primarily due to increased R&D expenses related to a collaboration with Arrowhead [41] - The company has a strong cash position with $647 million in cash and equivalents, plus an additional $600 million available through a revolving credit facility [36][42] Q&A Session Summary Question: What has been the biggest driver of potential downside pressure leading to revised guidance? - Management indicated that it is a mix of all three factors: cycle times, administrative processes, and the safety event, with cycle times being the most mechanically impactful [47][48] Question: How does the company direct patients to sites with more capacity? - Management clarified that it is more about focus and education rather than the number of sites, emphasizing the need to engage secondary sites more effectively [57][58] Question: What percentage of sales does Elevitus represent in the new guidance? - Management confirmed that the revision in total net product revenue was exclusively related to Elevitus, which is the primary driver of the guidance change [66] Question: What are the expectations regarding the potential label update for Elevitus? - Management stated that a labeling supplement was submitted in April, with a target review date set for no later than Q4 2025 [76]