Sarepta Therapeutics Q2 2026 Earnings Call Transcript

Quartr
Provided by Quartr
August 5, 2026

Key Takeaways

  • Negative Sentiment: 2026 net product revenue guidance was narrowed to $1.2 billion–$1.3 billion, with second-half revenue expected to be modestly below the first half and ELEVIDYS revenue likely lower in the third quarter. Management said improving enrollment forms may contribute more meaningfully to revenue in 2027.
  • Positive Sentiment: Sarepta reported Q2 GAAP operating income of $13 million and non-GAAP operating income of $86 million, while cash and investments increased by approximately $197 million to $945 million. The company also raised collaboration and other revenue guidance to $550 million–$600 million, primarily due to higher Roche contract-manufacturing revenue.
  • Positive Sentiment: ELEVIDYS enrollment-form activity improved sequentially as the expanded commercial organization became fully operational, with increased engagement from returning sites and interest from new referral sites. However, management cautioned that the typical approximately six-month enrollment-to-infusion timeline delays the revenue impact.
  • Positive Sentiment: The FDA accepted supplemental applications for AMONDYS 45 and VYONDYS 53 seeking conversion from accelerated to traditional approval, with a target action date of February 28, 2027. Sarepta said the applications are supported by the ESSENCE confirmatory study and substantial real-world evidence.
  • Neutral Sentiment: Key pipeline catalysts include second-half 2026 interim MAD-study data for the SRP-1001 FSHD and SRP-1003 DM1 programs, early Huntington’s disease proof-of-biology data expected in early 2027, and full 12-week data from ELEVIDYS ENDEAVOR cohort 8 expected in the first quarter of 2027.
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Earnings Conference Call
Sarepta Therapeutics Q2 2026
00:00 / 00:00

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Operator

Good afternoon. Welcome to Sarepta's Second Quarter 2026 Earnings Results Call. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Tam Thornton, Sarepta's Senior Director of Investor Relations. Please go ahead.

Tam Thornton
Tam Thornton
Senior Director of Investor Relations at Sarepta Therapeutics

Thank you. Thank you all for joining today's call. Earlier this afternoon, we released our financial results for the second quarter of 2026. The press release, along with our slides and supplementary information, are available on the investor section of our company website. We plan to file our Form 10-Q for the quarter today with the SEC. Joining me on the call are Michael Severino, our CEO, Dr. Louise Rodino-Klapac, President of R&D and Technical Operations, Patrick Moss, our Chief Commercial Officer, and Ryan Wong, our Chief Financial Officer. Additionally, joining us in the Q&A portion of the call are Ian Estepan, President and Chief Operating Officer, and Dr. James Richardson, Chief Medical Officer. Before we begin the formal remarks, I would like to note that during this call, we will be making a number of forward-looking statements.

Tam Thornton
Tam Thornton
Senior Director of Investor Relations at Sarepta Therapeutics

Please refer to slide two of our presentation to view the formal text of these safe harbor statements. These statements involve varying risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and such risks can adversely affect our business, our results of operations, and the trading price with Sarepta's common stock. We strongly encourage all listeners to review the company's most recent SEC filings for a detailed description of these applicable risks. Sarepta explicitly states that it does not undertake any obligation to publicly update or revise its forward-looking statements or financial projections based on subsequent events. Furthermore, please note that we will discuss non-GAAP financial measures during today's webcast.

Tam Thornton
Tam Thornton
Senior Director of Investor Relations at Sarepta Therapeutics

Complete descriptions and reconciliations of our GAAP to non-GAAP financial measures are included in today's press release and the accompanying slide presentation available to investors on our website. With that, I will now turn the call over to our CEO, Michael Severino.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Thank you, Tam. Good afternoon, and thank you for joining Sarepta Therapeutics' Second Quarter Financial Results Conference Call. This is my first earnings call as CEO of Sarepta. Today, I'll offer a few opening remarks and then turn things over to Patrick, Louise, and Ryan to discuss our commercial highlights, pipeline progress, and financial results for the quarter in more detail. As someone who has spent a career evaluating preclinical and clinical data and translating scientific breakthroughs into meaningful treatments for patients, it's an honor to be here. Sarepta is uniquely positioned within biotech and has tackled some of the most challenging problems in medicine. Our scientific achievements have helped redefine what is possible for patients with Duchenne, from pioneering work in exon-skipping to the development of ELEVIDYS. A growing body of long-term data has established Sarepta as a leader in rare disease innovation.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

I see tremendous potential untapped value in the opportunity we have in front of us, that is what brought me to be a part of this team. We have a leading commercial portfolio in Duchenne, with four approved therapies that are making a difference for patients today. These therapies are backed by a growing body of long-term data and real-world evidence supporting their use. We have an siRNAs platform that has already delivered strong preclinical and early clinical data. As a physician scientist, I find these data compelling and have been impressed by both the potency of our siRNAs constructs and our ability to deliver to the cell type of interest with high efficiency, as evidenced by our ability to achieve high muscle concentrations in a dose-dependent manner in our SAD studies.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Based on these features and the strong predictive value preclinical models have in this space, I believe our pipeline has the potential to deliver best-in-class therapies across multiple neuromuscular and rare disease indications, drive our next phase of growth. Importantly, we have the financial strength to advance these programs independently, we have a deeply experienced and talented team with a strong track record of delivering results. We recognize that concerns around ELEVIDYS adoption, competition on the horizon for exon-skipping treatments, and capital allocation remain. However, we are prepared to meet these challenges, have multiple upcoming milestones that can clarify our growth trajectory. These include Cohort 8 data, new data in the second half from two of our most advanced siRNAs programs in FSHD and DM1, and upcoming regulatory decisions around VYONDYS and AMONDYS. Turning our attention to the quarter.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

You will hear more details from Ryan shortly, I'd highlight three things from our quarterly financial results. First, we delivered another quarter of GAAP and non-GAAP operating profitability, reflecting the durability of our base business and disciplined execution. Second, we increased cash and investments by approximately $197 million during the quarter, strengthening our ability to fund future growth. Third, our commercial portfolio continues to provide a strong foundation as we invest in what we believe are significant long-term value and growth opportunities across our emerging siRNAs pipeline. Commercially, our PMO franchise has remained stable, ELEVIDYS performed in line with expectations, with improving enrollment forms providing early evidence that our expanded commercial initiatives are taking hold.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Now that we are in the second half of the year, we have narrowed 2026 total net product revenue guidance to $1.2 billion-$1.3 billion, with a midpoint being the appropriate reference. This is consistent with our prior expectation that results would trend toward the lower end of our original range. Patrick will provide more detail on our commercial performance, outlook, and growth initiatives in his section. Turning to R&D, we continue to make meaningful progress across both our Duchenne and siRNAs programs. In Duchenne, enrollment and dosing continue in Cohort 8 of the ENDEAVOR study, and we expect to fully enroll the study by the end of 2026. We were also pleased to see the FDA accept our sNDA submissions of AMONDYS 45 and VYONDYS 53 for review.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Beyond Duchenne, our emerging siRNAs platform remains central to Sarepta's future growth strategy, with important data readouts expected later this year from our FSHD and DM1 programs. Louise will discuss the biology-first approach that underpins these programs and why we believe our platform can deliver differentiated, potentially best-in-class therapies across multiple rare disease indications. In summary, our focus is clear and our future is bright. Our financial footing is sound, and we continue to execute in Duchenne. Revenue from our approved products enables us to advance our pipeline independently, which we continue to do with discipline and urgency. I'm excited to be on this journey with this team and look forward to creating long-term value for the company and the communities we serve. Thank you. With that, I'll turn it over to Patrick to discuss commercial performance for the quarter. Patrick?

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Thank you, Mike, and welcome to the team. Today, I'll review our second quarter commercial performance, the progress we are making to support physicians, patients, and families across our four approved Duchenne therapies, and our outlook for the remainder of 2026. For the second quarter, total net product revenue was $329 million, consisting of $98 million from ELEVIDYS and $231 million from our PMO franchise. PMO performance continues to reflect stable demand and sustained patient and physician confidence, supported by extensive real-world experience and evidence. ELEVIDYS performance was in line with our expectations for the quarter, with sales remaining relatively steady and quarter-over-quarter growth in enrollment forms signaling that demand is increasing. We view that trend as encouraging sign that momentum is building. Our focus is on sustaining that progress and supporting informed treatment decisions through continued science, education, and engagement.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Throughout the first half of the year, we completed the expansion of our commercial footprint. The strategy is set, our sales team is trained and deployed, and our initiatives are now fully operational. Our focus is now on execution, improving patient identification, expanding education for patients and families, and continuing to strengthen healthcare providers' confidence to drive demand. At a recent mid-year meeting, the energy across the team was clear. They are reaching more referring physicians, engaging more deeply at treatment centers, and participating in a more balanced discussion about the totality of evidence demonstrating ELEVIDYS's benefit-risk profile. In Q2, our sales team delivered a record number of HCP interactions. HCPs are engaging more deeply on the sustained functional outcomes and durability supported by ELEVIDYS EMBARK Part 2 and, more importantly, the three-year data. Enrollment form activity provides early evidence that these efforts are taking hold.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

A majority of Q2 enrollment forms were from HCPs who had interacted with our sales team in the prior 90 days, including a meaningful portion within 30 days. This pattern was consistent with Q1 and reinforces the importance of focused, timely engagement. The breadth of site activity expanded in Q2 as well, through both re-engagement and new interest. More returning sites submitted enrollment forms than in Q1, while submissions from referral sites outside our current network signaled broader interest in ELEVIDYS. Taken together, these indicators support our view that our sales team initiatives are taking hold. Understanding of the ELEVIDYS benefit-risk profile is improving, and confidence is rebuilding across the Duchenne community.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

In addition, our patient education team is bringing that same commitment directly to families, connecting with many who have turned to Sarepta seeking information that will help them navigate Duchenne and the treatment decisions they face with greater clarity and confidence. Turning to our outlook, as Mike mentioned, consistent with our previous direction of model towards the lower end of the $1.2 billion-$1.4 billion range, we are narrowing our 2026 total net product revenue guidance to $1.2 billion-$1.3 billion. The timing of revenue reflects how patients progress from enrollment form through the treatment journey. ELEVIDYS revenue in the first half of 2026 was supported by patients who entered the pipeline following the late 2024 label expansion and progressed to infusion during the first half of the year. As a result, first half revenue benefited from the conversion of that backlog of demand.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

ELEVIDYS revenue in the second half of 2026 will reflect a period when enrollment form activity was lower before our expanded commercial initiatives were fully deployed and beginning to take hold. We're encouraged by the quarter-over-quarter improvement in enrollment forms we are seeing today. However, given the length and variability of the treatment journey, that activity is expected to contribute more meaningfully to revenue in 2027. As a result, we expect total net product revenue in the second half of 2026 to be modestly lower than in the first half. We also currently expect ELEVIDYS revenue in the third quarter to trend lower than Q2, acknowledging that the quarter-to-quarter variability is the reality of a one-time gene therapy. We do remain confident in the long-term opportunity for ELEVIDYS, and our team remains focused on sustainable execution. Now, turning to our PMOs.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Stable demand, extensive real-world experience, a well-established safety profile, and adherence rates exceeding 90% continue to underscore the durability of this business. More than 1,800 patients worldwide have been treated with Sarepta's exon-skipping therapies, underscoring their enduring value to patients and families. This year marks an especially meaningful milestone for Sarepta and the Duchenne community. On September 19th, EXONDYS 51 will celebrate 10 years since its U.S. approval. For us, this is more than an anniversary. It represents a decade of Sarepta's leadership, close partnership with the Duchenne community, and progress that has helped us transform the treatment landscape. Over that time, Sarepta has helped establish exon-skipping as a foundational treatment approach and build a substantial body of real-world evidence across important outcomes, including ambulation, pulmonary function, cardiac function, and survival.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

We are proud of the progress made over that past decade and deeply honored to have served the Duchenne community throughout that journey. In closing, our priorities remain clear. Execute with discipline, support informed treatment decisions through science and education, and drive sustainable growth across our Duchenne portfolio. We remain confident in the long-term opportunity for ELEVIDYS and the strength and the durability of our PMO franchise. Most importantly, we remain deeply committed to transforming what is possible for patients and families living with Duchenne and bringing that same commitment to patients across other serious rare diseases. Thank you. With that, I'll turn the call over to Louise. Louise?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Thanks, Patrick. Let me add my welcome, Mike. We're happy to have you on board. As we move into the few last months of 2026, we remain excited by the science that underlies our rare disease portfolio and the data we're preparing to share with you soon. Before turning to the individual programs, I want to briefly frame how we think about our next-generation RNA platform. Our strategy is built on a simple premise, biology first. Rather than applying one delivery approach across all tissues, we select the receptor and delivery architecture that is intended to best address the key biological barrier in each disease. In muscle, that means leveraging alpha V beta six integrin targeting, which was selected for its strong muscle exposure and delivery characteristics. In the CNS, where the dominant barrier is transport across the blood-brain barrier, we use a unique transferrin receptor-based approach.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Across both settings, our goal is the same, to move beyond systemic exposure and achieve productive intracellular delivery, target engagement, molecular correction, and ultimately, the potential for functional benefit. Combined, we believe this approach will distinguish our therapies from others in earlier and later-stage development. This is also where siRNA biology is important. siRNA uses catalytic multi-turnover RISC activity that continually silence. We believe this enables deeper and potentially more durable suppression of disease-causing RNA than approaches that rely on antisense mechanisms that require RNase H, a rate-limiting enzyme. Together, biology-driven delivery and catalytic siRNA potency creates the foundation for our belief that these programs have the potential to be best in class.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Building on the positive SAD data from our lead programs to treat FSHD and DM1, we remain on track to announce interim results from our multi-ascending study or our MAD study in the second half of this year. We believe these programs are differentiated through a unique targeting mechanism and high muscle bioavailability, positioning them as potential best-in-class therapies compared to more mature competitor programs in this space. To remind you, data from our readout this year showed high muscle concentration with alpha V beta six and a strong safety profile. Beginning with SRP-1001, which is our siRNA-based treatment designed to reduce or knock down the production of the DUX4 protein in skeletal muscle in patients living with FSHD. FSHD is caused by abnormal activation of the DUX4 gene, leading to expression of the DUX4 protein. DUX4 is a transcription factor that affects the expression of multiple genes within muscle.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

It's normally expressed during embryonic development. When reactivated later in life, it creates a toxic intracellular environment that contributes to muscle degeneration. This underlying pathology is well understood, and the pathological role of DUX4 in the progression of the disease is well accepted. Our therapeutic thesis is that deeper DUX4 knockdown in muscle should translate into greater molecular correction, and over time, the potential for improved functional outcomes. The MAD data we plan to share will include safety, PK, DUX4-related gene panel, circulating DUX4-related biomarkers, CK, and preliminary functional assessments. Importantly, because FSHD is a slow progressive disease, and this is an early study including six months of follow-up, the objective is not to definitively demonstrate functional benefit at this time given the trajectory of the disease.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Rather, the goal is to establish the biological chain from tissue exposure to target knockdown to molecular biomarkers known to drive the underlying pathology of the disease, and also to select an appropriate dose to take on to the next stage of development. In summary, our goal is to generate the highest levels of knockdowns that improves biomarkers and leads to best functional outcomes. Confirming our ability to safely dose escalate and deliver a drug with proven biological efficacy efficiently to the target tissue would strengthen the evidence supporting SRP-1001 as a potentially best-in-class treatment for FSHD and provide an important foundation for our discussions with FDA as we prepare to advance a registrational study. Moving on to DM1. SRP-1003 is our siRNA-based treatment for DM1 designed to target and knock down or silence the DMPK mRNA in target cells.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

The early data we generated for DM1 is important for two reasons. First, our preclinical models are predictive of what we have seen in the clinic with respect to muscle concentration. Of note, an increase in plasma exposure has translated into enhanced dose-dependent delivery to the muscle, resulting in robust target engagement. Second, the DMPK knockdown observed to date has been directionally strong and supports the potential of siRNA to address the root molecular driver of disease. As you are aware, DM1 is driven by an expanded CUG trinucleotide repeat in DMPK transcripts, causing mutant DMPK mRNA to accumulate in the nucleus and disrupt normal RNA splicing. As a result, for any therapy to be therapeutically effective, it must reach the target tissue, enter the cell, and reduce nuclear retained DMPK RNA. SRP-1003 is being developed to achieve exactly that, with the goal of driving downstream splicing correction.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

The results we plan to share from the MAD study will include safety, serum and muscle PK, DMPK knockdown, CASI-22 splicing index, and vHOT analyses. The importance of these results, should they be positive, will differentiate SRP-1003 as a best-in-class treatment for DM1 and offer a clear path to a registration study. It's important to note that our FSHD and DM1 programs demonstrate why we believe delivery efficiency is a primary competitive advantage. The key differentiator is not simply reaching the bloodstream. It's reaching enough muscle fibers, maintaining exposure long enough, achieving sufficient intracellular siRNA concentrations, and driving meaningful target knockdown in the nucleus. Further, our non-clinical data has shown that targeting integrin receptors via small peptides leads to enhanced skeletal muscle uptake compared to using a much larger TFR1 antibody-based approach.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

It's also important to note that based on data to date, our alpha V beta six integrin targeting ligand provides superior muscle concentration compared to current transferrin-based approaches without dose-limiting toxicity. More specifically, due to its role in intracellular TFR1 trafficking, only approximately 5% of expressed TFR1 receptors are available on the cell surface for binding at any one time, versus alpha V beta six with approximately 40% of expressed receptors available at any one time. This high level of surface availability and high levels expression leads to a greater potential for ligands targeting alpha V beta six to drive significantly higher muscle uptake than TFR1. These delivery characteristics helped establish the rationale for advancing SRP-1001 for FSHD and SRP-1003 for DM1 in first-in-human studies and continue to support our confidence in the platform.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

In summary, we believe Sarepta's next generation RNA platform is differentiated by biology driven tissue targeting, efficient intracellular delivery, and the catalytic potency of siRNA. Our focus is on connecting the full chain from tissue delivery to target engagement to molecular correction and ultimately to the potential for functional outcomes. We're applying the same biology-first framework to our CNS programs. Our Huntington's program is ongoing, having dosed its first patients earlier this year. In these programs, our receptor selection is driven by the biological requirement for transport across the blood-brain barrier. If successful, the early CNS data would provide important validation of our transferrin receptor-based blood-brain barrier delivery approach. Our second generation DM1 program is the first example where we aim to impact the CNS in addition to muscle to address the significant unmet need. We look forward to sharing this data as soon as it becomes available.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Now turning to ELEVIDYS. We were pleased to announce in March that screening and enrollment were underway in Cohort 8 of ENDEAVOR for study SRP-9001-103. To remind you, the purpose of Cohort 8 is to assess prophylactic sirolimus treatment as part of an enhanced safety protocol during treatment with ELEVIDYS in nonambulant individuals with Duchenne. Data from Cohort 8 will be used to determine whether administering sirolimus prior to and after ELEVIDYS infusion can help reduce acute liver injury or ALI. A known risk associated with AAV gene therapy is a class effect. The cohort's enrolling approximately 25 participants in the United States who are non-ambulatory and dosing's currently underway. As a reminder, the immunosuppression regimen will include 14 days of peri-infusion sirolimus prior to ELEVIDYS administration and will continue for 12 weeks after ELEVIDYS administration. Primary endpoints include incidence of ALI and ELEVIDYS dystrophin expression at 12 weeks.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Participants will be followed for safety and functional outcomes for 72 weeks. The approach with sirolimus is based on pre-clinical data and shaped by real-world clinical experience, including guidance from independent specialists in Duchenne and liver health. The evidence base continues to build. As previously shared, there have been independent published reports on the use of sirolimus to mitigate ALI with ELEVIDYS. Dr. Soslow and colleagues very recently published a study in Human Gene Therapy demonstrating that none of the patients treated with prophylactic sirolimus had ALI. We will also present what we believe are encouraging interim safety data from our phase IV ENDURE study at the Neuromuscular Study Group meeting in September that showed zero incidence of ALI in patients treated prophylactically with sirolimus. We expect to fully enroll the ENDEAVOR Cohort 8 study by the end of 2026.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Based on observations that our study investigators are dosing participants sequentially, we now expect 12-week data from the full cohort in the first quarter of 2027. We continue to plan to meet with FDA in early 2027. In addition to safety, we continue to build the ELEVIDYS evidence base through upcoming disclosures. At the Neuromuscular Study Group meeting, key de novo disclosures include microdystrophin and muscle MRI correlations with function. Next, the impact of treatment delay modeling, the ENDURE phase IV interim safety and liver safety, U.S. post-marketing safety, and finally, the PROMISE mobility outcomes versus external controls. At the World Muscle Society meeting, we will highlight expression and safety data in ELEVIDYS-treated patients under four, along with encore presentations of EMBARK three-year outcomes, cardiac functional data, pooled safety, and early intervention preclinical data. We look forward to sharing this data with the community.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Moving now to AMONDYS 45 and VYONDYS 53, our exon-skipping therapies to treat Duchenne. At the end of June, we were excited to announce that the FDA accepted our supplemental new drug applications for both therapies. The filings produce a target action date of February 28, 2027. The sNDA submission seek conversion of the accelerated approvals of AMONDYS 45 and VYONDYS 53 to traditional approvals. The applications are supported by the data from the ESSENCE confirmatory study, as well as substantial published real-world evidence and the favorable and consistent safety profiles of both exon-skipping therapies. We look forward to sharing important updates with you in the coming months, including readouts from our FSHD and DM1 MAD studies, proof of biology from our Huntington's disease program, and data from the ENDEAVOR Cohort 8 study.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Thank you. I'll now turn the call over to Ryan for an update on our financial performance. Ryan?

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

Thank you, Louise. Good afternoon, everyone. We delivered a strong financial performance in the second quarter. We are pleased with the continued operating discipline reflected across the business. Our results underscore the durability of our commercial DMD franchise, the progress we are making with our pipeline, and our ability to fund our most important commercial and R&D initiatives from a position of financial strength. In my remarks, I'll walk through the quarter's key financial highlights and how we are positioned for the second half of 2026. Beginning with second quarter revenue performance. Total revenues were $401 million, a decrease of 34% year-over-year, driven by the decrease in net product revenues, primarily ELEVIDYS, due to lower demand. Total revenue in the quarter included $73 million of collaboration and other revenues, consisting primarily of contract manufacturing revenue from our partnership with Roche.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

Through the first half of the year, we have now recorded $659 million in total net product revenue and over $1.13 billion in total revenues. Q2 year-to-date total revenues decreased 17% compared to prior year, driven by lower ELEVIDYS product revenue, partially offset by higher collaboration and contract manufacturing revenues. Moving next to gross margins. Total cost of sales for the quarter were $149 million, a decrease of 2% compared to the prior year period. The change year-over-year is reflective of lower cost of goods due to a decrease in our product sales, partially offset by higher cost of goods related to contract manufacturing revenues. On a year-to-date basis, total cost of sales were $248 million, a decrease of 11% year-over-year, driven by similar dynamics. Gross margins on net product revenues were 75% in the quarter and 78% for the first half of the year.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

Operating expenses continue to reflect our focus on disciplined cost management. Combined R&D and SG&A expenses in the second quarter on a GAAP and non-GAAP basis were $199 million and $165 million, respectively. Non-GAAP expenses in Q2 decreased 44% compared to the prior year period, reflecting the benefit of our cost restructuring initiatives and the prioritization of our promising siRNA programs in our R&D portfolio. First half combined R&D and SG&A expenses on a GAAP and non-GAAP basis were $462 million and $388 million, respectively. Year-to-date, non-GAAP expenses were down 66% compared to the same period prior year, also driven by the restructuring and pipeline reprioritization, as well as the Arrowhead collaboration upfront expense recognized in the prior year. This operating discipline translating into meaningful profitability for the quarter. We delivered GAAP operating income of $13 million and non-GAAP operating income of $86 million.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

For the first half of the year, GAAP and non-GAAP operating income came in at a robust $372 million and $484 million, respectively. In addition to the results I just highlighted, our GAAP results include a $39 million litigation contingency charge to potentially resolve certain outstanding patent claims. From a balance sheet perspective, we ended the second quarter with $945 million of cash and investments, growing $197 million from the prior quarter. The robust cash increase in the quarter is a result of our strong operating performance and includes a receipt of $40 million from the Roche commercial sale milestone earned in Q1. For the first half of the year, if you exclude $250 million of collaboration payments made to Arrowhead in the first quarter, our base business has generated over $240 million in cash. In closing, I'll provide color on our outlook for the second half of 2026.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

First and foremost, we remain focused on disciplined execution, improving capital allocation as we advance our commercial and pipeline priorities. As you heard earlier on the call, we have narrowed our net product revenue guidance to between $1.2 billion and $1.3 billion with the midpoint of this range an appropriate reference. In addition, we are revising upward our total collaboration and other revenue guidance in between $550 million and $600 million, which is an increase of $75 million from the midpoint of our previous guidance. This is driven primarily by higher contract manufacturing revenues. I'd like to highlight for modeling purposes, this increase in expected contract manufacturing revenues will also result in a roughly equivalent increase in cost of goods for products sold to Roche. Now moving to expenses.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

Given we are halfway through the year, we are tightening our non-GAAP OpEx guidance to $800 million-$850 million, the low end of our previous range. Finally, from a cash flow perspective, looking back at the last 12 months, we have reset our cost structure, fulfilled our large collaboration obligations to Arrowhead, and refinanced the majority of our 2027 debt, while the base business generated nearly $400 million in cash. On a forward-looking basis, given the strength of our execution, we believe our medium-term liabilities and remaining 2027 notes are well-funded, and we remain in a strong financial position to fund our promising pipeline using cash flow from our business. With that, I'll turn the call back to Mike for Q&A. Mike?

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Thank you, Ryan. Operator, can you please open the call for Q&A?

Operator

Thank you. At this time, we will conduct the question and answer session. To ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We do ask that you please limit your questions to one question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Anupam Rama of JPMorgan. Your line is now open.

Anupam Rama
Anupam Rama
VP at JPMorgan

Hey, guys. Thanks so much for taking the question. Hi, Mike. How are you? Congrats on the new gig, man. When you look at the pipeline, what really excites you about what you have going on in the pipeline? Is it something particular about the Arrowhead products or something like what Cohort 8 could do for the ELEVIDYS franchise? I was wondering if you could expand on that. Thanks so much.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Certainly. Thanks for the question, Anupam, and I'm very happy to be here. There are a number of things that excite me about the pipeline. Maybe I'll talk about them in two parts. The Cohort 8 data, I think, are very promising. The potential for sirolimus to improve benefit risk in the non-ambulatory population, I think can have a big impact over time. Obviously, we're still in the data generation phase there, and as we said, we expect to complete that cohort's enrollment by the end of this year and have data in the first quarter of next year. I think that's something that we're very much looking forward to. When I look at the earlier pipeline and the siRNA programs that we're advancing, I believe they have tremendous potential.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

First of all, what I would say is in this space, preclinical models and early clinical data have a very high degree of predictive power. This is very different than what we see in most areas of drug discovery and development. We essentially know the biology that drives these conditions unambiguously. If we can achieve high levels of knockdown, we have a high degree of confidence that we can achieve a benefit for patients in the long term. When I look at both the preclinical data and the early clinical data, I see both the delivery aspects of the technology performing very well with dose-dependent increases in muscle concentration up to the highest dose tested in our SAD studies without any dose-limiting toxicities. We have very potent RNA silencing technology, as Louise pointed out. We are able to achieve very robust knockdown.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

I think there's a real opportunity to bring forward some tremendous therapies, not only in neuromuscular conditions, but also potentially in conditions like Huntington's, where our delivery technology also plays a key role in getting to deep brain nuclei in the preclinical models that we've studied. Obviously, that clinical trial is now underway to see how those data translate into the clinic. I just think there are a wide range of opportunities that can drive value for the company and value for patients in the future.

Operator

One moment for our next question. Our next question comes from the line of Kostas Biliouris of Oppenheimer. Your line is now open.

Kostas Biliouris
Kostas Biliouris
Managing Director for Biotech Research Team at Oppenheimer

Thank you for taking our question. Congrats on the progress, congrats on the new role, Michael. Welcome to Sarepta. A question for Michael. Based on our discussions, there is a high number of investors who are very interested in the DM1 and FSHD programs but are hesitating to underwrite the DMD pipeline risk. Although I understand it may be a little early for this question, how are you thinking about the potential separation of the two businesses, the DMD pipeline and the DM1 FSHD programs? Thank you.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

I think there's tremendous synergy between those aspects of what we do here at Sarepta in the big picture. We're very committed to Duchenne. We've been in Duchenne for more than a decade now. Our marketed products, we believe, are making a tremendous favorable impact on patients' lives. You see that in the long-term data. You see that in the preservation of function, increased duration of ambulation, reduction in progression of cardiac and pulmonary disease, and even overall survival across various aspects of our DMD portfolio. We think those programs are a real asset to the company. When we look at their performance, we see very solid, very stable, and very durable performance, which I think is very consistent with that benefit that is being delivered.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Importantly, the revenue that those programs generate is what allows us to drive the earlier parts of our pipeline, the siRNA programs in particular. They're really very complementary to each other. I think as we move through the year, we have a number of data readouts that will clarify the long-term role of our DMD portfolio, which I think is very promising and will have a very bright future, as well as turn over new important data cards on the siRNA pipeline that I think can open up some very new and very important venues for the company's future growth. Again, I think those areas are very synergistic.

Operator

One moment for our next question. Our next question comes from the line of Brian Abrahams of RBC Capital Markets. Your line is now open.

Brian Abrahams
Brian Abrahams
Head of Biotechnology Research at RBC Capital Markets

Good afternoon. Thanks for taking my question. Mike, congrats on the new position. Welcome to the Sarepta team. On the expense side, it looks like you've lowered your OpEx guidance for this year. I think you've talked in the past about the 800-ish range being a good steady state to think about. I'm curious if you could talk a little bit more about the puts and takes around the OpEx run rate here. Is there any further wiggle room? I guess how will resonance of the ELEVIDYS commercial efforts as well as the competitive dynamics for the exon skippers potentially influence how you think about long-term OpEx? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Ryan, do you want to take that?

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

Absolutely. Thanks for the question. We've talked previously around we're very comfortable in that $800 million-$900 million range in terms of OpEx, both being able to fund our commercial initiatives and to advance our pipeline. As you saw, we believe in the sort of durability of the DMD franchise. Although acknowledging that competitors are in the mix, we think there's high value in both our exon skipping and gene therapy programs. We're continuing to invest in that durable DMD franchise. Given the cash flow generation profile of our company, we feel really confident we can advance the siRNA programs to value inflection points. That being said, we continue to be very prudent about capital allocation.

Ryan Wong
Ryan Wong
CFO at Sarepta Therapeutics

We're going to think about where the science leads us in terms of what has the highest probability of success and what's going to ultimately generate long-term value for the company as we think about where we invest. That type of focus will continue to remain, even though we feel, again, very comfortable within that $800 million-$900 million range to advance our programs.

Operator

One moment for our next question. Our next question comes from the line of Andrew Tsai of Jefferies. Your line is now open.

Andrew Tsai
Andrew Tsai
Managing Director at Jefferies

Hi. Thanks. Good afternoon. Congratulations, Mike. I have a question about the regulatory strategy for the siRNA programs, because given you guys have the desire to start pivotal studies, can you maybe talk about your latest thinking and whether you plan to pursue accelerated approval or full approval for both indications? What do you envision your primary endpoint to be ultimately? Thank you.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

I'll ask Louise to address that.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. Thanks for the question. For both FSHD and DM1, in terms of the regulatory pathway, as we've thought about it and set it up, is that we have the ability to apply for both accelerated approval and traditional approval, depending on the regulatory framework at that time, the landscape, and the data that's generated. In terms of the outcomes that we will use in our phase III trial, that's really what the MAD study readout will help us inform of that. Obviously, in these early studies, we're looking at a variety of endpoints and evaluating all of them, and it'll be a data-driven discussion. We'll also be looking at the landscape in general. It's a great opportunity for both of these communities that there's so much interest in this space and so many developers in this space.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

It'll be both our internal data and the entire landscape that informs our approach to the next phase, and we look forward to having that discussion with regulators.

Operator

One moment for our next question. Our next question comes from the line of Ellie Merle of Barclays. Your line is now open.

Ellie Merle
Ellie Merle
Senior Biotech Equity Research Analyst at Barclays

Hey, guys. Thanks for taking the question. Michael, welcome to Sarepta. Just a clarification on some of your ELEVIDYS commentary. You mentioned you saw a quarter-over-quarter increase in ELEVIDYS enrollment forms. Just to clarify, are you also seeing an increase in start forms in 3Q versus 2Q, or if you could just characterize that trajectory. Then in your comments, you said you expect modestly lower ELEVIDYS revenue in the second half versus the first half, but more contribution from start forms in 2027. I guess, just to clarify, should we be expecting revenues to grow in 2027 from that? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

With respect to start forms up, I'll say a bit, and then I'll ask Patrick to provide some more detail. We were encouraged with the trends that we see. As you know, we spent a good portion of the first half of the year getting our expanded commercial footprint in place and putting our initiatives in place in order to have a balanced communication of benefit risk around ELEVIDYS. We're seeing those efforts start to take hold. We are seeing improvement in start forms, and we would expect those trends to continue. It's early to be talking about 2027, but we do feel quite confident in the nature of the benefit risk discussions that we're having and the trends that we're seeing. Patrick, do you want to add a little bit more detail?

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Absolutely. What I would say from a commercial perspective is the indicators that we're seeing today are moving in the right direction. Our strategy is set. Our sales team is trained and out there and deployed, and our broader commercial initiatives are fully operational. With the enrollment form activity, it has stabilized and improved. Returning sites are engaging, and we are seeing interest from new sites. I'd say all of this signals that these initiatives are taking hold and strengthening that patient pipeline, even though the associated revenue, it will come, but it's going to take time. Really, the team is just focused on consistent execution and helping those patients progress through the journey.

Operator

One moment for our next question. Our next question comes from the line of Yigal Nochomovitz at Citi. Your line is now open.

Caroline DePaul
Caroline DePaul
Assistant VP of Biotech Equity Research at Citi

Hi, this is Caroline on for Yigal. Thanks for taking our question. With DM1 and FSHD data approaching, can you tell us what disease characteristics make a target particularly well-suited for the alpha V beta six delivery platform, and what additional muscle diseases could become attractive expansion opportunities if the upcoming data sets are successful? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Certainly. Louise, would you like to take that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. For our platform for FSHD and DM1, we're using, and what really got us excited about working on these indications was the alpha V beta six targeting ligand. Really because of the wide distribution across muscle, that's why we selected it. We've also talked about the receptors available for high muscle concentration, that's exactly what we saw translating the preclinical data to early clinical data, is that we were able to achieve high levels of muscle concentration in DM1 and FSHD without dose-limiting toxicity. Really when looking at an indication why the alpha V beta six is attractive is because you are broadly getting high levels of muscle concentration. In terms of potential other indications, it's really those affecting muscle diseases with widespread need in terms of the muscle pathology.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

In now speaking to the other part of the equation with siRNA, DM1 and FSHD have very clear pathological roles by toxic gain of function, mRNA, DMPK, and then protein with DUX4. There, the technology to reduce, we know that it's due to this toxic protein or mRNA, we know that efficiently reducing that with the siRNA, the potent siRNA is important. It's those two things together. It's the targeting technology, it's the siRNA, then the ability to do that. With the alpha V beta six, you could target any muscle disease. With the siRNA, we're really looking at gain-of-function toxic diseases where you could get efficient knockdown of that indication. We're, as you can tell, really excited about this platform generally and the potential in these indications and beyond. Thank you.

Operator

One moment for our next question. Our next question comes from the line of Ritu Baral of TD Cowen. Your line is now open.

Ritu Baral
Ritu Baral
Managing Director and Senior Biotechnology Analyst at TD Cowen

Good afternoon, guys. Thanks for taking the question. Michael, great to have you in the seat. I've got two questions. One is related to just the time lag to revenues for ELEVIDYS. Given you guys mentioned that there is a quarter-over-quarter increase in demand, but that real revenue increases may not happen until 2027, does this imply that there is a longer time to fill, a longer time in the pipeline until revenue recognition than the previously indicated, I think, five-six months? Is that the lag we should be modeling going forward? With your Cohort 8 data in Q1 of next year, will you have expression data as part of that top-line release beyond just liver safety? If so, what should our expectations be both for expression and for liver safety? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Thank you. I'm happy to take those questions, and I'll ask Patrick and Louise to provide some additional detail. With respect to the time lag between enrollment forms and revenue, it's generally about six months, as we have said previously. There can be some variability around that, but it's typically around six months, and I think that's very consistent with what we're saying now that we're seeing enrollment forms improving. Given where we are in the year, that's going to translate into revenue meaningfully in the 2027 timeframe. There hasn't been any change there. Patrick, do you want to add any detail?

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Recent cohorts that have come in are not mature enough really to conclude whether the overall journey is getting longer or shorter; however, we continue to use that six months as the enrollment form to infusion for planning assumptions, knowing that timing is going to vary from patient to patient.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, do you want to take the question about the timing of expression data in Cohort 8?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. You asked about the endpoint. We expect to have the data on ALI, that's the primary goal of that study was to reduce that. We are collecting the biopsy data. At this point, I'm not sure about the timing of that data, but the primary goal of that readout, especially with taking data to the agency, will be for the ALI, and we will produce the biopsy data. I'm not sure on the timing of that at this point.

Operator

One moment for our next question. Our next question comes from the line of Mike Ulz of Morgan Stanley. Your line is now open.

Mike Ulz
Mike Ulz
Executive Director of Biotechnology Equity Research at Morgan Stanley

Good afternoon. Thanks for taking the question, and let me add my congratulations to Mike as well. Maybe just with respect to the RNA data updates expected later in the second half, should we expect those more towards year-end? Will you share those updates together, or do you plan to separate them out? If I remember correctly, I think FSHD may be a little bit ahead of DM1. Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

We've said that those data will be available later on in this year. At this point, we're not able to be more specific about the timing. We're going to look at each dataset as they become available and make them public in an appropriate fashion. I really can't comment today as to whether it would be at the same time or staggered. It depends on the availability of those data. Again, both are expected in the second half of this year, and we're on track to meet that timeline. Louise, is there anything you'd like to add?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

No, that's correct. Thank you.

Ian Estepan
Ian Estepan
President and COO at Sarepta Therapeutics

Hey, Ian, maybe just very quickly just to add, Mike's exactly right. We do think about these programs as separate programs, though obviously the timing on the SAD data, they were very close, and it made sense to release the data at the same time. Just generally speaking, we do think of these programs separately. To Mike's point, when they become available is likely when we would release it. That's how we're thinking about it generally as a program.

Operator

One moment for our next question. Our next question comes from the line of Salveen Richter of Goldman Sachs. Your line is now open.

Matt Dellatorre
Matt Dellatorre
Biopharma Equity Research Analyst at Goldman Sachs

Great. Thanks for the question. This is Matt on for Salveen. Building on a prior question, could you provide any more color on the metrics beyond start forms that you are seeing that support deeper ELEVIDYS penetration in the ambulatory patients? How are you thinking of the longer-term trajectory now? How might you be able to leverage some of your efforts here to support non-ambulatory use if that's eventually included back in the label? Thank you.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Absolutely. Our strategy is set. As I mentioned, the sales team is out there. They've been trained, they're deployed, and the broader commercial initiatives are fully operational. We're seeing enrollment form activity stabilize and improve. We've got returning sites that are re-engaging, and we're seeing interest from new sites. We're also seeing a directional alignment between healthcare provider engagement and enrollment form submission. When our sales team goes in and speaks with an HCP, we see enrollment forms result after, as I've mentioned, in some cases, as soon as 30 days after that engagement.

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

Those signals to us that those initiatives that we put in place are starting to take hold, and it's strengthening our patient pipeline, even though the associated revenue contribution, it's going to take time. Our team is just focused on consistent execution and helping those patients progress through the journey.

Operator

One moment for our next question. Our next question comes from the line of Biren Amin of Piper Sandler. Your line is now open.

Biren Amin
Biren Amin
Managing Director and Senior Research Analyst at Piper Sandler

Yeah. Hi, guys. Thanks for taking my questions. Maybe a three-parter from me. On AMONDYS and VYONDYS sNDA, has the FDA indicated if there are any plans to hold an advisory committee meeting? That's the first question. Second question on FSHDs. There's a direct transcriptional target of DUX4 that apparently correlates to clinical disease severity. I wonder if you're looking at that in the current trial. The last one on Cohort 8 data, is there potential to revive the LGMD gene therapy programs after those Cohort 8 data? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Okay. I'll start off. I'll pass to Louise. With respect to the AMONDYS and VYONDYS reviews, the FDA has not indicated at this time that they have an intent to schedule an advisory committee. Obviously, they can make that decision at any point. To date, they have not made any indication that they intend to do so. Louise, do you want to take the questions about the endpoints?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. The second question was on FSHD and the DUX4-related genes. Certainly we're looking at both a downstream DUX4 gene panel, but also, I think your point was around the DUX4 biomarkers. Our team is looking at multiple circulating biomarkers and evaluating them right now, both validating the assays and then looking at them in our models. Certainly that is something that we are actively looking at because having a circulating biomarker is a huge advantage in these indications. I believe the last question is on the limb-girdle pathway following Cohort 8 data. That's exactly right. For LGMD2E, as we've discussed before, right now we're on clinical hold, and in order to get off clinical hold and potentially submit the BLA, that's based on the Cohort 8 data, as we've discussed with the agency.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

As soon as we have that data, we'll be able to discuss the pathway to submit the BLA with FDA following that data as well.

Operator

One moment for our next question. Our next question comes from the line of David Hoang of Deutsche Bank. Your line is now open.

David Hoang
David Hoang
Director and Senior Analyst for Biotechnology at Deutsche Bank

Hi there. Thanks a lot for taking my questions. I want to ask about the PMO franchise and your perception of the durability there. In particular, how should we think about modeling the franchise next year, especially with EXONDYS, where we have a potential market entry of a competing exon 51 skipper. Thanks a lot.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

All right, I'll start and probably pass it to Patrick for a little bit more detail. We have a tremendous amount of confidence in the durability of the PMO franchise. This is a franchise that has a very long track record, 10 years for the first approval, and has delivered benefit to patients over that period of time. There's extensive real-world evidence supporting benefit as well as supporting a favorable safety profile. We feel that we are in a good position to enter a competitive market and to maintain momentum in that franchise. It's a bit early to predict exactly how those dynamics will play out from a modeling perspective, but we think any impact that competition would have would likely take some time to become visible. One has to overcome a number of hurdles when one enters a market like this.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

There are reimbursement pathways that need to be established, patient assistance programs that need to be put in place if the sponsor in fact intends to do that. For example, with our PMO franchise, we have home infusion support and a number of things that contribute in addition to the overall benefit delivered to the very high rates of adherence that we have observed, 90% or greater. We would expect that impact of competition, if it were to come, to be later on in 2027. Patrick, do you want to add any additional color?

Patrick Moss
Patrick Moss
Chief Commercial Officer at Sarepta Therapeutics

You covered it very well. Our position is grounded in that decade of experience supporting patients, families, physicians, and those treatment centers. As you mentioned, we've got a body of real-world evidence, established safety experience, adherence rates exceeding 90%. We've got a team that's very well-versed in working through any reimbursement challenges with the providers and the institutions in order to get patients authorized and reauthorized and keep them on therapy. All of that points to the mature infrastructure that we have and we're going to lean into as we support our patients.

Operator

One moment for our next question. My next question comes from the line of Mitchell Kapoor of H.C. Wainwright. Your line is now open.

Analyst at H.C. Wainwright

Hi, this is Jayden from Mitchell. Thanks for taking our question. Going back to AMONDYS and VYONDYS, regarding those sNDA submissions, do you have any thoughts on timing for converting EXONDYS to full approval? As you guys spoke about, as of next month, it'll have been on market for a full decade, but it's been on accelerated approval that whole time. Additionally, can you speak a bit on the recent Capricor AdCom meeting? Do you see this increased scrutiny of post hoc data reevaluation as a negative read-through for AMONDYS and VYONDYS, given that the data did not achieve traditionally accepted statistical significance in the trial? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

With respect to the Capricor AdCom, I think the issues that were discussed at that AdCom were particular to the package that Capricor brought forward, and the FDA's review of that package. Obviously, we don't comment on other sponsors' review process. We don't see read-through to our program. When we look at the applications, they are supported not only by the clinical trial data, but by extensive real-world evidence. We believe together, those present a strong package for conversion to traditional approval. With respect to the strategy for EXONDYS, Louise, would you like to take that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. For EXONDYS, we don't have a confirmatory study as part of that. We have a post-marketing commitment, which is our MISSION study, which is a dose-ranging study. That study will be done by the end of this year. Following that study, we'll have discussions with the agency in conjunction with the VYONDYS and AMONDYS as well. That's where we're at in terms of the potential conversion of EXONDYS to traditional approval.

Operator

One moment for our next question. My next question comes from the line of Andy Chen of Wolfe Research. Your line is now open.

Andy Chen
Andy Chen
Director and Senior Analyst of Equity Research at Wolfe Research

Hey, thank you for taking the question. Welcome, Michael. Regarding the MAD data in DM1 with the functional endpoint, I think, Louise, you mentioned that the primary goal is not to establish functional efficacy with the data set. Can you please clarify the reason behind it? Is it because you don't have visibility yet, and the sample size is too small for you to make a conclusion? Or is the empirical result tracking in such a way that you can't conclude that it's better than competition? Thank you.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Yep.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, do you want to address that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Yeah. For FSHD, it's really around the timing of the data. As I mentioned, FSHD is a very slow progressive disease, and its data is at six months. We would not expect to see a strong signal at six months. It's really about the timing of that. James, would you like to add anything around the disease itself and the way we think about functional outcomes in this indication?

James Richardson
James Richardson
EVP and Chief Medical Officer at Sarepta Therapeutics

I think you've covered it really, Louise. FSHD is a slowly progressive disease. We expect the treatment here to improve symptoms. We expect it to stabilize the disease, similar paradigm to DMD, and we need time for the disease to progress to show the therapeutic effects of stabilization. This is very much in line with other developers, further advances in the field as well.

Operator

One moment for our next question. Our next question comes from the line of Brian Skorney of Baird. Your line is now open.

Luke Herrmann
Luke Herrmann
Senior Research Associate of Biotechnology at Baird

Hi, this is Luke on for Brian. Thanks for the question, and also wanted to offer my congrats to Michael. On the Huntington's program, I guess do you have an idea of when we might see the phase I data? And can you remind us if you're measuring protein knockdown and if you think the study could support some initial biomarker proof of concept? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, do you want to take that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

We expect the first proof of biology data early next year. Really, this is early single ascending dose data. What we're looking for in this study is safety and then early signs of efficacy. Are we getting past the blood-brain barrier? To do that, we're looking at a knockdown of huntingtin, so that'll be in the CSF. That's what we'll be looking for in terms of validation of the platform, along with safety and the ability to dose escalate.

Operator

One moment for our next question. The next question comes from the line of Yanan Zhu of Wells Fargo Securities. Your line is now open.

Yanan Zhu
Yanan Zhu
Biotechnology Equity Research Analyst at Wells Fargo Securities

Oh, hey. Thanks for taking our questions, congrats to Mike on assuming the CEO role. A question on Cohort 8. Is the ALI data all that's needed from FDA to make a decision? If that's the case, could the decision be a reinstate the indication? Another question on the VYONDYS and AMONDYS, the sNDA. The review time seems to be eight months. I was wondering, it doesn't seem like either priority or standard review. Could you talk about what timeline is that and what might be the implication? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Certainly. With respect to Cohort 8, our strategy is to complete Cohort 8, and as soon as we have the 12-week data, approach the FDA to discuss the regulatory path. We can't comment on that regulatory path today, we will be engaging with regulators with data in hand to define that path. We believe that the Cohort 8 data, when they are available, together with other data sources like ENDURE, can make a compelling argument for benefit risk in this population. Obviously, that will be discussed with regulators, and the exact nature of the path will be defined at that time. With respect to the AMONDYS and VYONDYS review, it is a standard review.

Operator

One moment for our next question.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

No, I can clarify. Just it was 10 months from submission, not nine.

Operator

Our next question comes from the line of Tazeen Ahmad of Bank of America. Your line is now open.

Tazeen Ahmad
Tazeen Ahmad
Managing Director in US Equity Research at Bank of America

Hi. Thanks for squeezing me in. I just wanted to clarify, a comment that you made about the potential for an accelerated path for, let's say, DM1 in the future. It relates to the competitive landscape, if, let's say, one of the programs that's ahead of you in development, let's say Novartis, is able to get an accelerated path, do you think that would lessen the chances that Sarepta could have, even with compelling data, to get an accelerated path as well? Thanks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, would you like to take that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. As I mentioned, we'll evaluate the regulatory landscape as we proceed. Our study's designed to be ready and available for both accelerated or traditional. Certainly, having a traditional approval changes the landscape in terms of accessing an accelerated approval. It'll be facts and circumstances in terms of both the landscape and then where our data as well. We'll be looking at both to define that pathway, and it'll come out of discussions with the agency when we do so.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Agree with Louise. The only thing I would add, or perhaps emphasize, is that these will be data-driven decisions, so it will depend on the nature of an approval in this space, if that happens, and the particular strengths of our data relative to that approval. We will be prepared to go forward for either an accelerated or a traditional pathway, depending on what is most appropriate at the time.

Operator

One moment for our next question. Our next question comes from the line of Joe Schwartz of Leerink Partners. Your line is now open.

Joe Schwartz
Joe Schwartz
Senior Managing Director for Rare Diseases at Leerink Partners

Hi. Thanks for taking my question. Welcome, Mike. We appreciate you joining at such an important time and look forward to seeing how you shape the company's future. For the next SRP-1001 and 1003 updates, what quantitative benchmarks does each program need to clear to justify pivotal advancement rather than continued exploration?

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, would you like to take that?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. We're looking for two things out of these studies, or multiple things. We're looking for the ability to dose escalate safely, so get to a dose that's appropriate for the phase III with very strong muscle concentration and significant knockdown. As I mentioned during my opening remarks, we want to get the highest levels of knockdown that we can in order to affect the biomarkers and also predict functional improvement. That's all benchmarking back to our pre-clinical data. We're looking for muscle concentration, knockdown, and the ability to dose escalate safely, without any safety signals. That's what we're looking for out of these two studies.

Operator

Our next question comes from the line of Yun Zhong of Wedbush. Your line is now open.

Yun Zhong
Yun Zhong
SVP of Equity Research at Wedbush

Hi. Good afternoon. Thank you very much for taking the questions. The first question, I wanted to confirm because I thought the original guidance was for data from Cohort 8 to be available by year-end. Was there a delay in terms of the patient enrollment, and did you have any challenge to enroll non-ambulatory patient given the safety concerns? Secondly, can you remind us the efficiency of your Huntington's disease program candidate to cross the blood-brain barrier? In terms of knockdown efficiency, what magnitude would you like to see, please? Thank you.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Louise, would you like to take those?

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

Sure. For the Cohort 8 enrollment, in terms of enrollment, we're seeing the study progress well. We are seeing investigators dose sequentially their patients versus in parallel. When we looked at the timing of when we would have the 12-week data, it would be available in Q1 of next year. When we have the complete 12-week data from the 25 patients, that'll be in Q1. That's the reason for the data availability for Cohort 8. In terms of Huntington's program, the knockdown that we're seeing is really based on our preclinical models, and that's both in murine models as well as the nonhuman primate model, where we saw knockdown levels as high as 80%. Really what got us excited about this is the ability to knock down in the deep brain-like regions, the striatum, as well as the caudate.

Louise Rodino-Klapac
Louise Rodino-Klapac
President of Research and Development and Technical Operations at Sarepta Therapeutics

These are really what got us excited and what we'll be looking for. Obviously, in humans, we can't have that degree of certainty in terms of knockdown within the brain, so we'll be looking at CSF knockdown as a surrogate for that.

Operator

I'm showing no further questions at this time. I would now like to turn it back to CEO Michael Severino for closing remarks.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

Thank you, operator, and thanks to everyone on the call for your time and attention today. As I said in my opening remarks, my first few weeks with this talented team reinforced my view that we have a bright future ahead of us, and my confidence in the potential of Sarepta has only grown. We have four marketed products that make a real difference in patients' lives today. We have a compelling pipeline of siRNA therapeutics that will drive our future growth, and we are executing from a position of financial strength with the ability to advance our pipeline and initiatives independently, as evidenced by our strong balance sheet and operating profitability. A number of important catalysts are on the horizon, which we believe can unlock long-term value for patients and shareholders alike.

Michael Severino
Michael Severino
CEO at Sarepta Therapeutics

We appreciate your continued support and look forward to updating you on progress in the months ahead. With that, we can end the call, and I hope everyone has a very nice evening.

Operator

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Executives
    • Tam Thornton
      Tam Thornton
      Senior Director of Investor Relations
    • Michael Severino
      Michael Severino
      CEO
    • Patrick Moss
      Patrick Moss
      Chief Commercial Officer
    • Louise Rodino-Klapac
      Louise Rodino-Klapac
      President of Research and Development and Technical Operations
    • Ryan Wong
      Ryan Wong
      CFO
    • Ian Estepan
      Ian Estepan
      President and COO
    • James Richardson
      James Richardson
      EVP and Chief Medical Officer
Analysts
    • Anupam Rama
      VP at JPMorgan
    • Kostas Biliouris
      Managing Director for Biotech Research Team at Oppenheimer
    • Brian Abrahams
      Head of Biotechnology Research at RBC Capital Markets
    • Andrew Tsai
      Managing Director at Jefferies
    • Ellie Merle
      Senior Biotech Equity Research Analyst at Barclays
    • Caroline DePaul
      Assistant VP of Biotech Equity Research at Citi
    • Ritu Baral
      Managing Director and Senior Biotechnology Analyst at TD Cowen
    • Mike Ulz
      Executive Director of Biotechnology Equity Research at Morgan Stanley
    • Matt Dellatorre
      Biopharma Equity Research Analyst at Goldman Sachs
    • Biren Amin
      Managing Director and Senior Research Analyst at Piper Sandler
    • David Hoang
      Director and Senior Analyst for Biotechnology at Deutsche Bank
    • Analyst at H.C. Wainwright
    • Andy Chen
      Director and Senior Analyst of Equity Research at Wolfe Research
    • Luke Herrmann
      Senior Research Associate of Biotechnology at Baird
    • Yanan Zhu
      Biotechnology Equity Research Analyst at Wells Fargo Securities
    • Tazeen Ahmad
      Managing Director in US Equity Research at Bank of America
    • Joe Schwartz
      Senior Managing Director for Rare Diseases at Leerink Partners
    • Yun Zhong
      SVP of Equity Research at Wedbush
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