Sarepta Therapeutics, Inc. Q3 FY2025 earnings call

• Completed confirmatory study for VYONDYS and AMONDYS for ultra-rare diseases. Despite study missing statistical significance, data showed consistent clinical favorable trend, especially when excluding COVID participants and subgroup analysis. Real-world evidence supports the therapies with benefits like reduced risk of loss of ambulation, attenuation in pulmonary decline, etc. Compliance rate for weekly infusions is well over 90% commercially. • ELEVIDYS label: Had productive dialogue with OTP, expect label change process with FDA to be concluded soon. Agreed to black box warning for ALI and ALF, non-ambulatory removed from indication. Expert committee provided recommendations for ALF safety, including adding prophylactic sirolimus. Cohort 8 of ENDEAVOR study designed to demonstrate effectiveness of additional prophylactic immunosuppression in non-ambulatory patients. • Pipeline updates: SRP-9003 for LGMD Type 2E showed positive Phase III emerging data. siRNA pipeline advancing rapidly with DM1 and FSHD programs enrolling, anticipation of sharing initial results in Q1 2026, and plan to initiate Huntington's disease trial by year-end.

Notwithstanding unprecedented disruptions, ELEVIDYS and the PMOs together posted solid net product revenue of $370 million for the quarter. ELEVIDYS contributed $131 million, and the PMOs contributed $239 million. The PMO franchise delivered strong demand based on performance this quarter, with additional shipping days in Q3 benefiting performance.

• Expect Q4 infusion volumes to be flat to slightly down from Q3 due to market disruptions and seasonal dynamics. • Reiterates the ambulant population alone represents an annual revenue opportunity with a $500 million floor for ELEVIDYS. • Confident in the long-term opportunity for ELEVIDYS based on wealth of data demonstrating its benefits, and not anticipating the box warning in the final label to have a significant impact on prescribing behaviors.

• Study results missed statistical significance but had a clinically favorable trend. COVID impacted study results by reducing powering and including excluded patients. • Potential FDA actions changing standards or requirements for transitioning from accelerated to traditional approval. • Market disruptions in Q4 temporarily impacting demand generation and new enrollment forms for ELEVIDYS.

Q: What other endpoints should be looking for in a publication and/or medical conference presentation, FDA package supportive of the data presented?

A: ESSENCE has other secondary endpoints including functional and biological endpoints like expression. The final CSR will be presented to the agency and in medical meetings. Primary and secondaries favored the PMOs, and COVID-free population showed improvement in endpoints.

Q: How does the FDA look at the data sets with a p-value of 0.09 for the COVID-free population? What could be the potential outcome with the FDA decision?

A: FDA leadership noted 0.05 is relatively arbitrary for rare diseases and 0.09 could be acceptable. 0.09 is impressive considering 57 patients were excluded due to pandemic impact lowering study power. Believes there's no risk of losing marketing authorization and good argument for transitioning to traditional approval but can't predict in advance without agency review.

Q: What level of data to expect from the siRNA early programs?

A: Will share data from single ascending dose study, including safety, PK data (serum and muscle), and PD assays for knockdown and splicing. Working to validate and transfer assays for PD data to present in early 2026.

Q: Color on proposed sirolimus study trial design features and potential readout?

A: Protocol design similar to presented, minor back and forth with agency. Hoping to initiate study soon, with data potentially seen in first half of next year and full data set in second half of the year.

Q: Degree to which FDA's reaction to ESSENCE spills over to EXONDYS 51?

A: No immediate read-through. ESSENCE is specific to VYONDYS and AMONDYS, EXONDYS has a post-marketing commitment for dose-ranging study, which will be evaluated separately.

Q: When to expect data from patients receiving prophylactic sirolimus and expression data?

A: Expression data would be seen late next year after biopsy and analysis. The study on sirolimus is to enhance safety and may also show expression data, which is a next year event.

Q: Dynamics driving down quarter next quarter for ELEVIDYS?

A: Downstream impact from temporary pause in shipments, medical conferences, major holidays, and seasonal illnesses. These factors will temporarily impact demand generation and new enrollment forms.

Q: Color on ELEVIDYS demand normalization and impact of competitor therapies?

A: Early view supports the $500 million floor for ELEVIDYS. Trends in commercial execution and enrollment forms are positive, but no editorializing on other competitors' claims.

Q: Hard numbers on ELEVIDYS infusion postponements and start forms?

A: Not providing detailed numbers, but during pause had 14 cancellations, 11 rescheduled and redosed in August, remainder working through system. Revenue used as metric.

Q: Correlating ESSENCE interim AMONDYS data on biomarkers to final functional data?

A: Difficult to track due to not every patient having sequential biopsies. Once all final data is available, sensitivity analysis can be done to look at impact on dystrophin expression, but complicated by lack of sequential biopsies.

Q: Pickup in ELEVIDYS start forms and confidence in 2026 revenue?

A: Starting to see sites identify patients and send in enrollment forms. Early trends support positive outlook, but more data will be shared later, likely at JPMorgan time frame.

Q: Prescribers using sirolimus prophylactically for ambulatory patients and thinking around non-ambulatory risk?

A: Anecdotal evidence of some physicians using sirolimus prophylactically, finding it manageable. Study on non-ambulatory patients will determine if risk benefit justifies use, with results to be reviewed and potentially leading to resuming dosing non-ambulatory patients.

Q: Interaction with FDA regarding ESSENCE trial and percent of patients missing consecutive doses in non-COVID group?

A: No specific discussions with agency regarding ESSENCE over last 6 months. Percent of patients missing consecutive doses more than doubled in COVID period versus COVID-free period.

Q: Insight on FDA look at MISSION trial data for EXONDYS and post-trial meeting?

A: FDA will look at totality of evidence from MISSION to see if increasing dose to 100 mg per kg provides benefit. If data shows benefit and risk benefit justifies, will consider distributing at higher dose. Meeting with agency after trial to discuss next steps.

Q: Degree of factoring competitive pressures from emerging therapies in ELEVIDYS floor assumptions?

A: Considered emerging therapies, but floor assumption is a stress test, not guidance. Comfortable with $500 million floor as it's a financial shape that allows maintaining revolver and advancing programs.