Sarepta (SRPT) Q4 2025 Earnings Call Transcript

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DATE

Feb. 25, 2026 at 4:30 p.m. ET

CALL PARTICIPANTS

• Chief Executive Officer — Douglas Ingram
• Chief Commercial Officer — Patrick Moss
• President, Head of R&D, Chief Scientific Officer — Dr. Louise Rodino-Klapac
• Chief Financial Officer — Ryan Wong

TAKEAWAYS

• Cash & Investments -- $954 million at year-end, increasing $89 million in the fourth quarter.
• Net Product Revenue (2025) -- $1.86 billion, comprising $966 million from PMOs and $899 million from ELEVIDYS; additionally, $334 million in collaboration, contract manufacturing, and royalty revenue from Roche.
• Guidance: 2026 Net Product Revenue -- $1.2 billion to $1.4 billion, with management stating to "model toward the low end of the range at least for the time being."
• ELEVIDYS Q4 Revenue -- $110 million, directly impacted by a severe flu season and rescheduling of six infusions into 2026.
• PMO Franchise Q4 Revenue -- $259 million, stable from 2024; individual PMO breakdown: $148 million for EXONDYS 51, $134 million for VYONDYS 53, $77 million for AMONDYS 45 (component figures do not sum as multiple PMOs overlap).
• Operating Profit & Cash Flow Outlook -- Management expects to deliver operating profit and positive cash flow in 2026; base business generated more than $330 million of positive cash flow in 2025, excluding Arrowhead payments.
• Gross Margin -- Excluding period charges, unit sales-driven margins in 2025 were in the low 80% range. Management expects 2026 margins in the high 70% range as production volumes decrease.
• Inventory & Supply Charges -- Q4 included a $193 million charge: $165 million non-cash reserves for excess inventory and $28 million for purchase commitment cancellation fees.
• Cost Management -- Combined non-GAAP R&D and SG&A expenses for Q4 were $413 million; full year 2025 non-GAAP expenses were $1.85 billion ($884 million related to Arrowhead collaboration); core operating expenses $965 million. 2026 non-GAAP operating expense guidance reaffirmed at $800 million to $900 million.
• Total Year Revenue (2025) -- $2.2 billion, up 16%.
• Debt Refinancing -- $291 million of 2027 notes refinanced into 2030, with $159 million remaining; management describes the remaining stub as "very manageable."
• ELEVIDYS Clinical Data -- Three-year EMBARK Phase 3 data showed a 73% slowing of disease progression (Time to Rise) and a 70% slowing (10-meter walk/run) versus controls, with a 4.39-point North Star Ambulatory Assessment difference (p=0.0002).
• ELEVIDYS Safety -- "No new safety signals were observed in three years after treatment and no treatment-related serious adverse events were reported;">1,200 patients treated.
• PMO Compliance -- Year-after-year compliance rates "consistently over 90%" per management.
• ESSENCE Study -- Confirmatory results for AMONDYS and VYONDYS read out; FDA meeting to discuss potential traditional approval scheduled for Q1.
• ELEVIDYS Label & FDA Actions -- ELEVIDYS granted updated label and "traditional approval for all ambulatory patients four and over" following 2025 safety events and label changes.
• Cohort 8/ENDEAVOR -- Sirolimus pretreatment study for nonambulatory patients enrolling; results expected by end of 2026.
• Roche Collaboration: Japan Launch -- ELEVIDYS launched in Japan; $40 million milestone payment expected upon first commercial sale in Q1 2026.
• Other 2026 Roche Revenue -- $125 million anticipated from Roche declining an option for a specified program; total collaboration, contract manufacturing, and royalty revenues for 2026 guided at $450 million to $550 million.
• siRNA Pipeline -- Five clinical-stage programs advancing, including DM1, FSHD, IPF, SCA2, and Huntington’s disease; proof-of-concept readouts for DM1 and FSHD expected by end of Q1; study SRP-1005 for Huntington’s accepted by Medsafe in New Zealand, with dosing to commence H1 2026.
• 2026 Q1 Revenue Guidance -- Q1 expected to be "about flat to perhaps down 15%" compared to Q4 2025.
• CEO Transition -- Douglas Ingram announced intent to retire as CEO by end of 2026; a search for a successor is underway.

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RISKS

• Severe flu season and six delayed infusions directly impacted ELEVIDYS Q4 revenue, with management noting that "a few patients move one way or the other on the therapy" can noticeably affect quarterly results.
• $193 million Q4 charge for excess inventory and purchase commitments, driven by lower-than-anticipated demand and manufacturing recalibration.
• Management stated, "2026 serves as a critical reset year," citing an "information imbalance" and lingering physician and patient hesitancy toward ELEVIDYS after 2025 safety events and FDA actions.
• Management guided toward the "low end of the range," indicating that delays in educational initiatives and long infusion cycles may lower near-term revenue realization for ELEVIDYS.

SUMMARY

Sarepta Therapeutics, Inc. (NASDAQ:SRPT) reported significant Q4 and full-year 2025 revenue growth, improved liquidity, and strong cash flow as it heads into 2026, while proactively addressing prior safety concerns and operational challenges. Management highlighted the successful transition of ELEVIDYS to a traditional label for ambulatory patients, upcoming confirmatory discussions with the FDA for two PMOs, and robust new clinical data in Duchenne muscular dystrophy. Leadership emphasized major shifts in commercial strategy to resolve lingering information deficits impacting treatment adoption, while also advancing a deep siRNA pipeline and preparing for CEO succession after Douglas Ingram’s planned retirement.

• Management forecasts Q1 2026 revenue to be "about flat to perhaps down 15%" from Q4, reflecting volatile near-term demand dynamics.
• Roche collaboration expands with ELEVIDYS launched in Japan, unlocking a $40 million milestone in Q1 and contributing to a total projected $450 million-$550 million in partnership revenue streams for the year.
• Pipeline milestones for DM1, FSHD, and Huntington’s disease are anticipated in 2026, with key proof-of-concept data for siRNA modalities expected imminently.
• A $193 million charge from excess inventory and supply recalibration reflects post-2025 manufacturing adaptation and highlights a risk factor for margin volatility.
• Douglas Ingram’s pending CEO retirement by end of 2026 marks a major leadership transition, with an active search underway for his successor.

INDUSTRY GLOSSARY

• PMO (Phosphorodiamidate Morpholino Oligomer): Synthetic RNA analogs used for exon-skipping therapy to modulate pre-mRNA splicing in diseases like Duchenne muscular dystrophy.
• ELEVIDYS: Sarepta’s gene therapy for Duchenne muscular dystrophy, recently granted traditional FDA approval for ambulatory patients age four and older.
• siRNA (small interfering RNA): Double-stranded RNA molecules used to induce targeted gene silencing through mRNA degradation, under development for rare neuromuscular and genetic diseases.
• NSAA (North Star Ambulatory Assessment): Functional scale used to evaluate motor abilities in patients with Duchenne muscular dystrophy.
• EMBARK: Phase 3 global study investigating efficacy and safety of ELEVIDYS in Duchenne muscular dystrophy patients.
• ENDEAVOR: Open-label study evaluating ELEVIDYS in nonambulatory Duchenne patients, including Cohort 8 with sirolimus pretreatment.
• ESSENCE: Confirmatory Phase 3 study evaluating efficacy of Sarepta’s PMO exon-skipping therapies.
• FSHD: Facioscapulohumeral muscular dystrophy; a rare, progressive genetic muscle disease and focus of Sarepta’s siRNA pipeline.
• DM1: Myotonic dystrophy type 1; a severe genetic condition targeted by Sarepta’s investigational therapies.
• DMPK: Dystrophia Myotonica Protein Kinase; a gene targeted in DM1 therapy development.
• DUX4: Double homeobox 4; a gene whose misexpression causes FSHD, serving as a therapeutic target.
• Acute Liver Injury (ALI): Sudden onset of liver dysfunction, a monitored safety endpoint in gene therapy trials.
• SRP-9003: Sarepta’s gene therapy candidate targeting limb-girdle muscular dystrophy (LGMD2E).

Full Conference Call Transcript

Douglas Ingram, Dr. Louise Rodino-Klapac, Patrick Moss, and Ryan Wong. After our formal remarks, we will open the call for Q&A. I would like to note that during this call, we will be making a number of forward-looking statements. Please refer to Slide 2 on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta Therapeutics, Inc.'s control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations, and trading prices for Sarepta Therapeutics, Inc.'s common stock.

For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today, based on subsequent events or circumstances. As noted on Slide 3, we will discuss non-GAAP financial measures on this webcast. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website. I will now turn the call over to our CEO, Douglas Ingram, who will provide an overview of our recent progress.

Douglas Ingram: Thank you, Tamara. Good afternoon, and thank you for joining Sarepta Therapeutics, Inc.'s fourth quarter and full year 2025 financial results conference call. As you will hear today, we have entered 2026 on a strong footing. There are three pillars to our strength. Our first pillar is our financial position. As our CFO, Ryan Wong, will discuss in more detail, because of the actions we took in 2025, we entered 2026 in a solid financial position with a large and growing cash balance, significant revenue, positive operating cash flow, and removal of any near-term debt overhang. We exited 2025 with $954 million in cash and investments, growing $89 million in the fourth quarter.

We anticipate under all reasonable scenarios to be cash flow positive and profitable on a non-GAAP basis this year, even as we fully invest in our pipeline and our marketed therapies. Our second pillar is our four durable life-improving therapies. As you will have seen, our three approved PMOs have remained stable even in the face of ELEVIDYS cannibalization. We read out the results of our AMONDYS and VYONDYS confirmatory study ESSENCE late last year, and we have scheduled a meeting with the FDA for later this quarter to discuss the potential to transition those two therapies to a traditional approval. When one considers the PMOs, it is important to recall several things.

The PMOs have been serving the Duchenne community well for many years now, in some cases, exceeding a decade. Over these many years they have been on the market, there has accumulated an exceptional body of published real-world evidence consistently showing the significant disease-moderating benefits of these therapies across measures and across organ groups. And ESSENCE is supportive of the risk benefit of these therapies. Patients and their physicians see significant value in the PMOs, as represented by year-after-year compliance rates consistently over 90%. Indeed, families are fiercely supportive of these therapies. And importantly, the safety profile of the PMOs over the last decade is stellar.

For these reasons, the evidence supports, and we think the time has come, to transition AMONDYS and VYONDYS to a traditional approval, although we do stand ready to provide additional reasonable prospective real-world evidence, if ultimately required. Moving on to ELEVIDYS. The unanticipated, and in two instances, tragic events of 2025 created uncertainty around ELEVIDYS in the middle of last year, but much of that uncertainty has been cleared by now. While short-lived, FDA actions caused questions about the future availability of ELEVIDYS. That is now resolved with an updated label, updated precautions and monitoring, and a traditional approval for all ambulatory patients four and over.

The FDA has approved our sirolimus pretreatment study for nonambulatory patients, which is an important step on the potential pathway back to treating nonambulatory patients assuming a successful outcome. That trial is already enrolling patients, and we expect results by the end of this year. Once we have the data in hand and assuming its success, we will discuss with the FDA the fastest possible pathway forward to resume commercial dosing in the nonambulatory populations. Those results will also be an important element of moving forward with our BLA for SRP-9003 to treat LGMD2E. Over 1,200 patients have already been treated with ELEVIDYS and yet the majority of patients remain to be treated. That is an enormous opportunity.

As we addressed the issues of 2025, we were left with little time to provide balanced information on the safety and efficacy of this simply remarkable therapy. And that information deficit has resulted in some patient and physician hesitation that must be addressed to ensure the greatest number of Duchenne patients benefit from ELEVIDYS. We have well-designed plans to address information deficits so that families and treating physicians are fully armed with accurate and balanced information to inform the decision to treat with ELEVIDYS. In a moment, Patrick Moss, our Chief Commercial Officer, will walk you through our plans.

Equally important, the overwhelming evidence that ELEVIDYS significantly alters the course of this disease has only grown over the last year with updated three-year EMBARK data that was universally positive and showing that the gap between ELEVIDYS-treated Duchenne boys and those who unfortunately have not yet been treated grows greater and greater with every passing year. These plans will take some time to execute given both the timing of the plans and the long cycle nature of start form to infusion, but based on the market research and advisory boards we have conducted, we are confident about our plans.

We previously chose not to provide guidance on total net product revenue for 2026, due primarily to the uncertainty on the timing of our ELEVIDYS initiatives. However, we will provide broad guidance today to help investors model the year. Now while it is challenging to perfectly model the exact shape of the revenue curve of a one-time therapy like ELEVIDYS, we believe there is a significant opportunity among the prevalent and incident population over the next three-year horizon.

The delay and impact of our initiatives may affect near-term sales, but they should not impact the ultimate opportunity as we expect to pick up those sales as our initiatives result in better understanding of the disease-modifying benefits of this therapy, and a compelling need to treat as soon as possible. But that is not to suggest that we will be satisfied before all patients and physicians have the information they need to make informed decisions about this therapy. Regardless of our long-term sales, every day that goes by without treatment, a boy or young man loses muscle that he can never get back.

Patrick will discuss this in more detail, but given the timing of the initiatives and the long cycle time for ELEVIDYS, we do not expect that we will begin to see the impact of our educational efforts until at least well into the second half of this year. Looking at the first quarter itself, we should achieve revenue that is about flat to perhaps down 15% from the prior quarter. For total net product revenue for the entire year, we are providing a guidance range of $1.2 billion to $1.4 billion for our approved therapies. To be clear on our expectations, without our educational efforts, we would expect to track to $1.2 billion in net product revenue for the year.

Depending on the timing of the initiatives, that could be as high as $1.4 billion if the initiatives more immediately showed impact. But given the long cycle times I just outlined and the resulting quarter-to-quarter variability, we believe that it is prudent to model toward the low end of the range at least for the time being. While we are being disciplined in our near-term projections, our confidence in the ultimate demand for ELEVIDYS and the transformational nature of this therapy remains exceptionally strong, and we believe our initiatives will support this opportunity. Now the third pillar of our company is the strength of our pipeline. We have an exciting siRNA pipeline that is advancing.

We have now five clinical-stage programs including our neuromuscular programs for DM1 and FSHD, our pulmonary programs for IPF, and our CNS programs for SCA2, and now for Huntington's disease. Given the unique approach we are taking with the Arrowhead TRiM platform, these programs hold the potential to be best-in-class. They also hold the potential to bring a better life to more than 160,000 patients in the United States and multiples of that number internationally. We have two additional programs completing preclinical work for deadly CNS diseases, that is SCA1 and SCA3, and we have additional discovery programs with Arrowhead for high-value targets across neuromuscular and cardiac and CNS diseases.

We are making good progress with our siRNA programs, and we will have some important updates this year as Dr. Rodino-Klapac will discuss later in this call. And with that, let me turn the call to our Chief Commercial Officer, Patrick Moss. Patrick? Thank you, Doug, and good afternoon, everyone. As preannounced in January, net product revenue for 2025 totaled $1.86 billion.

Patrick Moss: As preannounced in January, net product revenue for 2025 totaled $1.86 billion consisting of $966 million from our PMO franchise and $899 million for ELEVIDYS. For the fourth quarter, net product revenues for the PMOs totaled $259 million, which is relatively stable compared to 2024. Individual PMO net product revenues were $148 million for EXONDYS 51, $134 million for VYONDYS 53, and $77 million for AMONDYS 45. Turning to the ELEVIDYS performance, fourth quarter revenues totaled $110 million impacted by the severe flu season and six planned infusions that had to be rescheduled in 2026.

Now looking forward, it is important to recognize that the $500 million revenue floor for ELEVIDYS reflected a steady-state mix of incident patients along with a meaningful contribution from the prevalent ambulatory population. The safety events of 2025 reshaped the perceptions of gene therapy and of ELEVIDYS specifically. As a result, it has become more clear to us that 2026 serves as a critical reset year for the ambulatory patient population, where there is an information imbalance and the disease-modifying benefits of ELEVIDYS are less understood. Patients need and deserve a clear and comprehensive understanding of ELEVIDYS' risk-benefit profile to have informed and thoughtful conversations with their physicians.

Physicians also deserve to be armed with a full understanding of the data and the totality of the evidence to help patients make the best treatment decisions. Thankfully, we have a robust and growing body of data for ELEVIDYS. Two-year data for EMBARK Part 2 has recently been included in our promotional efforts, and the three-year EMBARK top-line data we shared last month will be presented at the upcoming MDA conference. Both the two- and three-year data show sustained ELEVIDYS benefits over time, with evidence of slowed disease progression versus natural history. I do need to emphasize something that matters, something that truly matters to patients, and that is the significance of the muscle MRI data.

Our muscle MRI data is powerful in that it provides unbiased evidence showing the difference between those treated with ELEVIDYS versus untreated Duchenne. The muscle MRI data shows that muscle decline is evident well before functional decline is observed, and delaying treatment results in irreversible muscle damage that cannot be restored. This is empirical evidence that reinforces the importance of preserving muscle by treating Duchenne as soon as possible. Clinicians have affirmed their belief in the data and the disease-modifying effects of ELEVIDYS through feedback at advisory boards and conference discussions. Their clinical experience is consistent with the data.

Yet they believe, as we do, there is still work to be done to ensure patients have a balanced view of the benefit-risk profile of ELEVIDYS. Our newer commercial initiatives are squarely focused on addressing the information deficit by reengaging with our customers with enhanced messaging and an expanded footprint of our field teams. The traditional approval of ELEVIDYS creates a meaningful opportunity to strengthen our commercial messaging and engage customers in new ways. We have updated our materials with substantial new data from the two-year EMBARK results to improve clarity and support a balanced understanding of ELEVIDYS' benefit-risk profile.

And as a reminder, ELEVIDYS is the only FDA-approved gene therapy for Duchenne and has treated more than 1,200 patients across clinical trials and commercial settings with that number continuing to grow. In addition to updating our messaging, expansion of our customer-facing teams enables us to go beyond treatment centers to educate referring physicians, patients, and their caregivers. Our teams are addressing treatment hesitancy through accurate and clear information with a repetition that supports informed decision making. The decision by a patient and their caregiver to pursue gene therapy is an important one.

Our outreach to clinicians, caregivers, and patients is designed to address what is on their minds at each of these stakeholders, and support them with educational efforts, resources, and data. We remain confident that our new 2026 initiatives will benefit patients while recognizing that it will take time for these efforts to translate into accelerated new patient demand. Unlike chronic therapies, which benefit from an installed base, ELEVIDYS is a one-time therapy and each treatment represents a new patient start. We continue to believe there is significant opportunity for ELEVIDYS, and our confidence in capturing that opportunity is supported by emerging green shoots.

A meaningful proportion of recent enrollment forms this year have come from sites that have not submitted since last summer, and a growing percentage of enrollment forms have come from sites outside of our existing network. While this early traction from new sites is encouraging, we remain focused on executing our commercial initiatives to accelerate demand across the treatment network. The PMO franchise remains stable in 2026, with demand declining modestly year over year as patients choose ELEVIDYS. This durability continues to be a testament to the clinical value of protecting muscle to slow the decline of Duchenne through the use of exon-skipping therapy and the relentless operational excellence of the team.

We are comfortable with the current consensus estimates for our PMO core in 2026. Now in closing, we are energized by the stability of our PMO business and the opportunity created by the traditional approval of ELEVIDYS. The robust long-term data included in our updated ELEVIDYS messaging, our expanded field force, and demand from the Duchenne community support our efforts. Our confidence for 2026 is heightened by what we have witnessed: the ability to change the arc of the relentless decline of Duchenne.

Our execution is driven by our commitment to serve patients, and we draw our inspiration from them, their families, and the clinicians who continue to share their stories on how our treatments are changing what we know about Duchenne.

Douglas Ingram: I will now turn the call over to Louise.

Dr. Louise Rodino-Klapac: Thanks, Patrick. I am happy to share with you our progress over the last several months, beginning with the positive top-line three-year functional results from Part 1 treated patients in EMBARK for study SRP-9001-301, our global randomized placebo-controlled Phase 3 study evaluating ELEVIDYS in ambulatory individuals with Duchenne. Sarepta Therapeutics, Inc. has led what is the largest and longest-running Phase 3 trial, making ELEVIDYS the most studied gene therapy in Duchenne.

We were thrilled to share the results last month, which showed that three years after treatment, patients who received ELEVIDYS in Part 1 of EMBARK demonstrated statistically significant, clinically meaningful, and durable efficacy across all key motor function measures, which include North Star Ambulatory Assessment, Time to Rise, and 10-meter walk/run, when compared to a prespecified propensity-weighted untreated external control group. The mean NSAA score remained above baseline at year three for the ELEVIDYS-treated group, while the external control group continued to show the expected age-related decline below their baseline score.

Specifically, the ELEVIDYS group showed a 73% slowing of disease progression as measured by Time to Rise and a 70% slowing of disease progression as measured by the 10-meter walk/run when compared to the external control group. The North Star Ambulatory Assessment showed a 4.39 difference at year three between the treated and external control group, with a highly significant p-value of 0.0002. To put into context the importance of these results, please note that functional outcomes like Time to Rise and 10-meter walk/run are prognostic for delayed loss of ambulation. Slowing disease progression is expected to help preserve functional abilities for longer and delay more debilitating stages of disease.

The EMBARK data show that as ELEVIDYS continues to slow disease progression and the cumulative benefits increase over time, a greater divergence from natural history occurs as patients in the external control group progress into the declining phase of the disease. Further, as Dr. Crystal Proud, a pediatric neurologist, EMBARK investigator, and someone who has treated many Duchenne patients stated, she has witnessed the transformative impact of ELEVIDYS for her Duchenne patients who can now do many daily activities in ways we would not expect. In children who have not received treatment with ELEVIDYS, as they get older, these functions decrease exponentially as the disease progresses.

Further, no new safety signals were observed in three years after treatment and no treatment-related serious adverse events were reported, which is consistent with our understanding of the safety profile of ELEVIDYS, as evidenced by more than 1,200 patients treated clinically and commercially. These data support ELEVIDYS as a disease-modifying therapy, providing a clear and growing benefit over time in those treated versus those untreated. I would also like to provide a brief update now on Cohort 8, which is part of our open-label study ENDEAVOR for study SRP-9001-103. As a reminder, as of July 2025, we treated 155 nonambulatory patients with ELEVIDYS before dosing was paused.

This new cohort, Cohort 8, was designed to assess the impact of a sirolimus treatment regimen on reducing acute liver injury, or ALI, a known side effect of all AAV gene therapies. Cohort 8 will enroll approximately 25 U.S. patients who are nonambulatory. Our primary endpoints are dystrophin expression at 12 weeks and the effectiveness of sirolimus on the incidence of ALI. We initiated this trial in late 2025 and are currently screening patients for enrollment. We expect to share findings by the end of 2026. Moving now to the 2026 MDA Clinical and Scientific Conference, which will take place in Orlando, Florida from March 8 through March 11.

Sarepta Therapeutics, Inc.'s robust presence at this year's conference will include important highlights across our portfolio. Of note, the three-year EMBARK functional data, including cardiac safety data, will be presented. We will also have several presentations from our PMOs demonstrating real-world evidence of long-term benefit along with our Phase 3 ESSENCE results. Turning now to our PMOs and an update on our exon-skipping therapies, VYONDYS 53 and AMONDYS 45, to treat patients with Duchenne amenable to exon 53 or 45 skipping, respectively. We believe the totality of the data we have generated to date with real-world evidence is compelling. Our meeting has been scheduled with FDA, and it will take place towards the end of Q1.

We have also submitted a briefing book. Moving now to siRNA. Our DM1 and FSHD programs continue to advance. As announced in November, our Phase 1/2 single ascending dose and multiple ascending dose clinical study of SRP-1003 to treat DM1 is progressing well. Cohort 1 and Cohort 2 of the study are complete, and Cohorts 3 and 4 are fully enrolled and ongoing. Dosing in the final cohort, Cohort 5 at 12 mg/kg, will be initiated by the end of the month. For FSHD, enrollment in our SAD study is complete, and Cohorts 5 and 6 of our MAD study are fully enrolled.

We are excited by the potential of these programs to offer differentiated profiles, including better safety and greater muscle concentration over other therapies currently in development. Specifically, we look forward to evaluating our early proof-of-concept data to establish the αVβ6 targeting ligand as a potential best-in-class approach for muscle penetration and corresponding ability to dose at levels required for maximum knockdown. As previously communicated, we plan to announce our preliminary data from our proof-of-concept studies for DM1 and FSHD programs at the end of this quarter. Of critical importance will be the safety and PK data. We expect to have serum and muscle PK to validate preclinical dose model prediction and evaluate dose response.

Preliminary PD data will be valuable to further support our models to inform Phase 3 trial design. We look forward to sharing these early results with you. Moving now to our Huntington's program, SRP-1005. We have initiated our trial for Huntington's disease using SRP-1005. It is an investigational siRNA therapeutic for the treatment of Huntington's disease. This program utilizes a subcutaneous route of administration allowing for target engagement in deep brain regions like the striatum, particularly affected in Huntington's. The Huntington's gene located on chromosome 4 produces the huntingtin protein, which is vital for neuronal development, signaling, and survival.

Last month, we announced the submission of our clinical trial application for study SRP-1005-101, also known as INSIGHT, to Medsafe, New Zealand’s medicines and medical devices safety authority. They have accepted our application, and our next milestone is to commence dosing in the first half of this year. As you can see from this slide, we have numerous value-enhancing milestones coming up over the next 12 to 18 months. We are particularly excited about the promise of our advancing siRNA pipeline and continuing to add to the robust body of evidence for ELEVIDYS and our PMO exon-skipping therapies. In closing, I would like to take a moment to recognize Rare Disease Day, which takes place on Saturday, February 28.

We are reminded that when it comes to rare disease, we must look for the unexpected and think beyond the common answer of diagnosis. The zebra has become a symbol for rare diseases, reminding us that, like a zebra’s stripes, every rare disease patient’s journey is unique. To those living with rare disease, we see you, and we are with you. Thank you, and I will turn the call over to Ryan Wong for an update on our financials. Ryan?

Ryan Wong: Provided details for the fourth quarter and full year on a GAAP basis as well as a non-GAAP basis are available on Sarepta Therapeutics, Inc.'s website for full results. My appreciation to the Sarepta Therapeutics, Inc. team for their continued dedication and diligence in driving our goals forward. We took decisive actions to reduce our cost structure and proactively address our 2027 debt, supporting long-term financial resilience. We expect operating profit and cash flow through 2026 with a solid foundation to execute against our goals. By way of our 2025 performance, I will share some forward-looking perspective for 2026. For full year 2025, total revenues were $2.2 billion, an increase of 16% year over year.

This included $1.86 billion in net product revenue and $334 million in collaboration, contract manufacturing, and royalty revenue from our partnership with Roche. Looking ahead to 2026, in addition to our net product revenue guidance of $1.2 billion to $1.4 billion, I can share further detail on our expectations for other revenues. As noted in our press release yesterday, ELEVIDYS is now launched in Japan. In Q1 2026, we expect to record a $40 million milestone payment from Roche upon the first commercial sale. Additionally, we anticipate recognizing $125 million of non-cash collaboration revenue tied to Roche declining an option for a specific program.

Altogether, we expect total collaboration, contract manufacturing, and royalty revenues in 2026 to be in the range of $450 million to $550 million. Moving on to gross margin, in the fourth quarter, total cost of sales was $399 million, a significant increase over the prior year. During Q4, we conducted a review of our raw material inventory and adjusted purchase commitments to avoid carrying materials that would expire before use. This review resulted in a $193 million charge consisting of $165 million in non-cash reserves for excess inventory and $28 million in purchase commitment cancellation fees. For the full year, cost of sales totaled $840 million.

Nearly half of this amount reflects failed production batches, inventory reserves, and other period charges associated with recalibrating our go-forward manufacturing plans. Excluding these charges, our unit sales-driven margins were in the low 80% range for the year. Despite the immediate impact to margins in 2025, we expect improved margins and fewer period charges in 2026, as production volumes will be significantly lower than in prior years, as we were building ELEVIDYS inventory for a broad ambulatory and nonambulatory population last year. On a unit-volume basis, we expect 2026 margins in the high 70% range.

Shifting to expenses, combined non-GAAP R&D and SG&A expense in the fourth quarter were $413 million, driven in part by the $200 million second DM1 milestone under our collaboration with Arrowhead. For the full year, non-GAAP expenses totaled $1.85 billion, with $884 million related to the same collaboration. Excluding Arrowhead, our core operating expenses were $965 million. Consistent with cost reduction targets we announced last July, we are reaffirming our 2026 non-GAAP operating expense outlook of $800 million to $900 million. Rounding out the P&L for 2025, we reported a GAAP operating loss of $700 million and a non-GAAP operating loss of $492 million.

Adjusting for restructuring and Arrowhead transaction expenses, our underlying business would have delivered its second consecutive year of positive operating profit: $226 million on a GAAP basis and $391 million on a non-GAAP basis. Turning to the balance sheet and cash flow, in the fourth quarter, we completed a second debt exchange transaction refinancing an additional $291 million of the 2027 notes into 2030. This leaves the remaining $159 million stub that we believe is very manageable given the cash generation profile of our business. We ended the year with $954 million of cash and investments. Ex Arrowhead payments, our base business generated more than $330 million of positive cash flow in 2025.

In closing, as we move through 2026, we will continue to focus our resources on initiatives that drive demand for our on-market therapies and advance our pipeline toward key value inflection points. We remain committed to disciplined financial execution and to delivering sustained non-GAAP operating profit and positive cash flow. And now I will turn the call back to Doug for closing remarks. Doug?

Douglas Ingram: Thank you, Ryan. Before we open the call to questions, I want to share an update regarding my own plans. By this summer, I will have had the privilege of leading Sarepta Therapeutics, Inc. for some nine years now. It has been, without a doubt, the single honor of my professional life to serve alongside this extraordinary team. Over those nine years, we set audacious goals for ourselves, chief among them, the goal of lessening the burden and extending the lives of boys and young men with Duchenne muscular dystrophy.

And along the way, as you all know, we solved many thorny scientific and technical problems even as we faced and overcame many exogenous and extraordinary obstacles, challenges that would have undone a less committed, less creative, less resilient organization. And yet this team that works with me and for these families never wavered. They innovated. They executed. They often pulled off what others saw as improbable or even impossible, but because of that commitment, we now have four approved therapies, and thousands of boys and young men with Duchenne are living more vibrant lives today than would have been imaginable a decade ago.

And that impact can count, not only for those families, but for those yet to be treated and for a generation of future patients who will benefit from the foundation that we have built. Despite an unusual market dynamic that has not yet caught up, Sarepta Therapeutics, Inc. is in fact stronger today than just about any other point in its history. We are on a strong financial footing, with four approved therapies bringing a better life to patients, an exciting pipeline of clinical-stage siRNA programs, and one of the strongest, most passionate, and committed teams in our history.

For that reason, and after a lot of thoughtful consideration, I have informed the Board that I intend to retire as CEO, and I intend for that to occur by around the end of 2026. This decision was a deeply difficult one for me, as this is the most meaningful and rewarding role that one could imagine, and we stand at one of the most exciting moments in our entire history. However, I have family commitments that require my attention, and I will explain them even though I am normally a relatively private person.

When I joined Sarepta Therapeutics, Inc., I had no personal connection to dystrophy, but through my work at Sarepta Therapeutics, Inc., I have developed a passion for our quest to improve the lives of those living with muscular dystrophy. I doubt anyone who knows me would disagree with that. That commitment required nearly my exclusive time in Boston and Cambridge while my family primarily resides in California. As you know, in late 2024, we entered into a partnership with Arrowhead and we gained access to a number of very promising therapies, including SRP-1003 for the devastating disease DM1.

Well, subsequent to that partnership, in a fairly shocking and certainly ironic twist of fate, my personal commitment to muscular dystrophy has deepened, as two members of my immediate family have been diagnosed now with myotonic dystrophy, DM1. By the end of 2026, the time will have come for me to spend more time in California focusing on family commitments and addressing the realities of DM1. The Board and I have initiated a comprehensive search for my successor both internally and externally. We will seek a visionary leader, someone capable of maximizing this team's potential, accelerating our opportunities, and one who is unwaveringly committed to this extraordinarily important Sarepta Therapeutics, Inc. mission that we have.

When I eventually leave this role, it will be with complete confidence in this team and in Sarepta Therapeutics, Inc.'s trajectory, first and foremost in fulfilling our mission to lessen the burden of devastating diseases and ultimately in delivering the value that our science and execution warrant. Thank you for indulging me. And with that, let us turn the call to questions. We will now open for questions.

Operator: As a reminder, to ask a question, press 1-1 on your telephone and wait for your name to be announced. To remove yourself, press 1-1 again. In the interest of time and as a courtesy to other analysts, we ask that you please keep your questions to one. One moment while we compile the Q&A roster. First question is from Anupam Rama with J.P. Morgan. Please proceed.

Anupam Rama: Hey, guys. Thanks so much for taking the question. Doug, I was wondering if you could speak to how you think about and how the Board thinks about internal versus external candidates as you go into your retirement. The company is in a place where, you know, you are still, you know, coming out of a tough period for ELEVIDYS in 2025. You know, you have to defend your PMO franchise. You have to deliver on the Arrowhead assets. Right? And how do you think about continuity with somebody like Ian Estepan, for example, who has been forward facing with the street, forward facing with the patient community, forward facing with the KOL community. Your partners know him.

Versus bringing in someone externally who may break that continuity?

Douglas Ingram: Well, thank you for your question, Anupam. Look, I would just say in the broadest of strokes that the Board is looking for both internal candidates, taking that very seriously, and looking at external candidates at the same time. Certainly, we are at a very important point in our history. We have a lot to do and a lot of execution to do, and I think we will have to be very mindful that whoever we choose, whether internal or external, understands what we are up against and understands how to execute and understands how to lead this team and shares our cultural values, which, while that sounds very soft, is an exceptionally important and important part of this company.

I think the thing that fuels us and allows us to keep going even in the face of oftentimes very challenging obstacles that occur when you are the leader is this patient focus that we have. So, I can at least commit to all of you that I and the Board understand where we are as an organization, and we are going to be very thoughtful that we choose a person that can continue to drive us forward and execute these plans and get the most out of this team. I mean, I will just linger for a second, and, hopefully, any Sarepta Therapeutics, Inc. employees that are listening to this call will listen and hear me.

This is the most exciting time we have as an organization, and this is one of the most impressive teams I have ever had the good fortune of working with, and I have had a lot of teams in my many years now. I have been doing this now for three decades, and I have had a lot of really impressive teams that have worked for me. None are as impressive as this team.

So we have a lot to execute and a great team, and whoever we ultimately choose to be the successor CEO, I am confident will be a person that can drive our plans, can speak as a leader to this great team, and can get the most out of an exceptional team.

Anupam Rama: Thank you. And, Doug, I am so sorry about your family as well. And so

Douglas Ingram: Yeah.

Anupam Rama: Our thoughts are with you.

Douglas Ingram: Thank you all. Bye-bye.

Operator: Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Please proceed.

Brian Abrahams: Hey. Good afternoon. Thanks for taking my question. Doug, thanks for the heartfelt message, and my best wishes to your family as well. With regards to the kind of renewed efforts around messaging for ELEVIDYS, what are some of the key metrics that you are going to be looking for over maybe the first half of this year that might suggest initial receptivity? And what are some of the takeaways we should think about from some of these signals you discussed with new sites initiating start forms, and the return of some sites that had not prescribed since the summer? Thanks.

Douglas Ingram: Yeah. Those are very good questions. I am going to turn this over to Patrick for a more detailed answer. In the broadest of strokes, the ultimate signal is going to be embedded first and foremost in enrollment forms and then ultimately in infusions. But there are probably many signals we can get long in advance of that through the use of things like regional advisory boards and market research and the like to really see that people are beginning to fully embrace and understand the data on this therapy.

I mean, it is remarkable how much data we have on the completely trajectory-changing benefits that come from this therapy, and really being able to contextualize that for having people fully understand that is an exceptionally important issue. But with that, Patrick, you can provide certainly more detail than I can on this topic.

Patrick Moss: Agreed. And, really, what we do is we consider there is value in promotion. Right? And so our team is just beginning to get out there and promote the value of ELEVIDYS with our updated traditional label. And so our promotional efforts, they are rooted in the strong data, and that data continues to show the value of restoring dystrophin using ELEVIDYS. But one thing I would also point out is that, you know, this is rare disease and more specifically a one-time therapy in rare disease. So each patient is a new patient. It is not a refill or script renewal. So efforts do take time. And so a small number of patients can impact performance.

And so all those various metrics we do evaluate as we are looking at our performance.

Douglas Ingram: Thanks very much.

Operator: Our next question comes from the line of Eliana Merle with Barclays. Please proceed.

Tejas: Hi. This is Tejas on for Eliana. Thanks for taking our question. For the siRNA readouts in Q1, are there any particular benchmarks we should keep in mind when we think about target engagement? Should we think of these doses as getting to a therapeutic level, or if not, what levels could we see that read well to higher doses?

Douglas Ingram: I am going to turn this question over to Dr. Rodino-Klapac. I will speak in the broadest of strokes and, again, I am going to preview this, and then Dr. Rodino-Klapac is both going to correct anything I say that is incorrect and provide far more informed views.

But if you think about the main conceit of these therapies, particularly our muscle-directed therapies, DM1 and FSHD, the unique thing about these therapies is that they employ the integrin receptor in a very specific way, which at least preclinically would suggest a number of things, that you can do this very safely, and that at equivalent doses, you can get much greater concentration, which means that ultimately you should be able to dose escalate even more significantly with more headroom, and you should get much greater and at the same time safe knockdown and then downstream splicing, which means that in these early days of the readout, the two things we should be looking at most significantly are safety and muscle concentration.

Because if you have a very safe therapy or a relatively safe therapy and you have great muscle concentration, you know, at low doses, then, you know, Occam’s razor, the rest will come, including the downstream splicing, and the functional benefits and the like. So those are the big things to look at, and we will have more than that, but those are the big things to look at. But I will turn it over to Dr. Rodino-Klapac to provide her views.

Dr. Louise Rodino-Klapac: Thank you, and I do not need to correct anything. I will just add a few things in the fact that certainly we are looking for muscle concentration, and based on our preclinical data, and data from the SAD data so far, we can continue to dose escalate. The important thing is also getting muscle concentration and also because we are using siRNA and we know how potent they are, we are not limited by the cellular machinery like an ASO where they are reliant on the RNase H in order to create knockdown. And so using siRNA, we are not limited by that.

So taken together, those two things, so both muscle concentration and the ability of siRNA to produce efficient knockdown, we feel optimistic based on our preclinical data to be able to continue to dose escalate and potentially provide best-in-class knockdown. That is what we are looking for, is consistency with the preclinical data. Most of the data will be the SAD data. Obviously, that is one dose, and we will continue to get data throughout the year on the MAD as well, which we will further evaluate.

Operator: One moment for our next question. That comes from the line of Andrew Tsai with Jefferies. Please proceed.

Andrew Tsai: Hey, thanks. I appreciate the update, Doug. Wishing you and your family all the best. So I also wanted to ask on the siRNA readout strategy in general. When would you be prepared to start pivotal studies? I think I heard you mention the word pivotal for DM1 and FSHD. Would it be right after the full MAD data set in second half, or do you need to do more dose expansion work? And then I am also curious your latest thinking on the accelerated approval pathway for these indications. In DM1, I think one company is going after accelerated, the other full approval. So I would love to know what your stance is. Thanks.

Douglas Ingram: I will turn this over to Louise.

Dr. Louise Rodino-Klapac: Yeah. So, first on the Phase 3. So in my script, I indicated, yes, we are working towards the Phase 3. We will be continuing the MAD study, which will inform that. And at the same time, we are getting ready on the manufacturing side for Phase 3, again so that we can make sure that we are ready to go with commercial-ready material for that Phase 3 and can move as fast as possible. So we are, as you would predict, moving as fast as possible.

In terms of the potential for an accelerated approval, it will be facts and circumstances depending on where we are at with the state of the environment with other companies and where they are with approval. I think with FSHD, for example, there is early potential readouts that would not have a long delay between accelerated and traditional approval. We are taking our fastest approach regardless of whether we ultimately end up getting an accelerated versus a traditional approval, and we will do so and make sure that we are collecting the appropriate data, functional data, to support both.

Operator: Our next question comes from the line of Joe Schwartz with Leerink Partners. Please proceed.

Joe Schwartz: Thanks so much, and please accept our condolences and best wishes, Doug, for you and your family. I was wondering if you could talk a little bit about how clinicians are currently risk stratifying patients for ELEVIDYS using things such as liver enzymes, age, weight, steroid exposure, concomitant meds, etcetera. How has your view of ideal candidates changed based on the experience that is building currently?

Douglas Ingram: Yeah. Let me say one thing, and I will turn it over to Patrick to answer the details. I do not think that our view has changed, whether what the current state in the market may be before more education occurs. You know, it may be different than that. But just to be clear, we think there is this enormous opportunity. As we said, the vast majority of the addressable ambulatory patient population remains to be dosed, and we are confident that all those patients would benefit. We will not get all of those patients.

I am not unrealistic, but we can get a lot of those patients when everybody understands the context and understands the benefits of this therapy and understands the compelling need to dose as soon as possible. And I think the muscle MRI data, maybe more than any other single piece of objective empirical evidence, tells us that you need to dose as soon as possible to save muscle before it is lost. But we have work to do there. And in the interim period, I think, Patrick, maybe you can talk to how you see physicians stratifying patients and excluding and including patients and the like.

Patrick Moss: Yeah. In addition to that, Doug, what we see is with Duchenne, obviously a rare disease that impacts the entirety of the family. And so it is really each patient; they have a unique situation. So there is travel, schedule, siblings. And so all of that is contemplated as a physician and the patient family decide whether they are going to move forward and at what rate.

Douglas Ingram: Yeah. We do see, I think, you know, some physicians without more information, meaning younger, and so we have got to think about that and work with physicians, show them the data, understand the risk-benefit of this therapy so that they and their patients can make better informed decisions across the entire ambulatory spectrum. One additional thing that we cannot and will not promote because it is currently not in our label, but it is occurring exogenous to us, is that about 25% of sites today, and I suspect that is growing, are proactively using sirolimus, either prophylactically before dosing or reactively if they see, for instance, an increase in liver enzymes.

And that practice may also over time impact the patients that physicians see as amenable for this therapy. Thank you.

Operator: Thank you. Our next question comes from the line of Johann Kim with Citigroup. Please proceed.

Johann Kim: Hi. This is Johann Kim on for Ygal. Thanks for taking our question and wishing you and your family the very best, Doug. One quick one from us. We are just wondering if you could provide some context on the size of the Japanese market, whether there are any important ordering dynamics to note, and then broadly speaking, any color on the potential for nonambulatory patient treatment in Japan and what additional activities you would need to do. What would need to be done to be able to enable that.

Douglas Ingram: Yeah. Patrick, do you have any perspective on the size of the Japanese market other than the broad perspective that Japan is obviously one of the highest-value countries from a pharmaceutical perspective that exists across therapies? But do you have any more information than that, or should we turn folks to Roche for a better understanding of that?

Patrick Moss: I would turn them over to Roche.

Douglas Ingram: Okay. We are excited, as you all know. Our partner is launching that therapy in Japan. Japan is an extraordinary opportunity, very large population, very advanced health care system, understands the value of therapies and how to price therapies as a culture. And, of course, there are a lot of boys and young men in Japan who are living with Duchenne muscular dystrophy who will benefit from this therapy. So we are very excited about not merely the opportunity, but the ability to do some good in Japan.

Operator: Got it. Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed.

Tommie M. Reerink: Thanks for taking our questions. This is Tommie on for Salveen. We are just hoping for some more details on ELEVIDYS’ quarterly dynamics. So your guidance of the Q1 being flat to 15% down, how do the rescheduled infusions play into that? And just checking on some of the math, you are assuming $900 million in PMO revenue, giving you an ELEVIDYS range of around $300 million to $500 million. Maybe you can give some more detail on how the timing of that acceleration and kind of magnitude in the second half of the year plays in.

Douglas Ingram: Yeah. I will give you the broad strokes, and then, again, Patrick may have more color for you. As we look across the year, the first thing to consider on a quarterly basis, if we say we are going to be flat to slightly down, is that given this is a rare disease and given the cost per patient, a few patients move one way or the other on the therapy. Also, you will know that six patients were delayed into 2026 from 2025, but also understand there is always this knock-on effect. So that to the extent you are able to dose a patient in the first quarter that was delayed, that will almost delay another patient.

So it does not just become additive. But, ultimately, the patients will be there. I think we already—and, Patrick, you will correct me if I have this number wrong—but we have already dosed three of those patients who were delayed into 2026. And then there are two things to know on those ranges, the sort of $1.2 to $1.4 billion. It does relate to ELEVIDYS more than the PMOs. The PMOs are very stable, and they are easier to forecast because they are chronic therapy.

So you tend to be forecasting on the margins of a therapy as opposed to what you have to do with a one-time therapy like ELEVIDYS, which is basically you start new every quarter, and then you have to forecast that way. So $1.2 billion implies that we are at steady state with no new educational efforts of any benefit. Our educational efforts should drive awareness and understanding of the risk benefits and should drive patients to get in front of the doctors and doctors to be starting more enrollment forms, and that gets you up toward the $1.4 billion. But as we have said, you have to be thoughtful about the lead time on these.

The initiatives themselves take lead time. We already hired up our salesforce. We have a contract salesforce. We have patient educational liaisons that we are going to be hiring. We have promotional material, but all of that requires training and getting out there and getting it through the process. And that takes its own time to be meaningful and impactful. But then the enrollment-to-infusion time is itself something in the, you know, at the very lowest, four months to even six months.

So all of that suggests that for planning purposes, you should assume that while we will get signals that this is really working in the next quarter or two, to really see that turn into revenue is going to be something that is going to occur significantly into 2026. So that is kind of the delta between the $1.2 to the $1.4 billion. Patrick, you may have other metrics that you think I have missed.

Patrick Moss: Yeah, I mean, you hit most of them, and I would really start off to say that with ELEVIDYS the quarter-to-quarter dynamics, as you mentioned, they can be noisy. Right? And so we have to consistently look at performance over the longer arc rather than each quarter. With the identification and screening of the patients and ultimately dosing, that can lead to that variability. But what we are focused on is to ensure that our team is out there executing on our plan, out there engaging with physicians, with payers. We are coordinating with the sites, supporting the patients, and all of that remains solid.

Douglas Ingram: Yeah. One other thing to know. We talk a lot about getting the information out there and really educating people, getting them to understand the risk-benefit of this therapy and understand all of the efficacy data that we really had little time to do in 2025, for all of the reasons you know about. We were dealing with a lot of issues. We were working with the agency. We were getting the label updated and the like. And, of course, it did not allow us the time to really do this. Plus, we have more data today than we ever did before. The one-year data looked brilliant. The two-year data looked exceptional.

We just got the three-year data, and it is just—the gap is growing and growing and becoming obvious that these patients really, if they understood this data, need to understand that they need to get in there and get infused. But there is another big issue as well on this issue of educating and information. And that is—and this I find really troubling—that you have a much better chance of getting infused with ELEVIDYS if you are middle class, English speaking, well educated.

There is a real delta that exists where people that are not in the middle class, Spanish speakers, other people in a different socioeconomic environment, just may not even have access to any information to be able to make thoughtful decisions about the therapy. We are going to address that this year. We have some very good plans to address that and to really serve the full community, not pieces of the community. One thing on the Spanish-speaking side, we are really focusing in on ensuring that we have a lot of field salesforce that speaks Spanish, that can talk to people where they are.

We have other thoughts about how we can support people that are struggling but have children with Duchenne, which is very, very common, frankly. And so that is a big part of the efforts. It is not merely just more and more information, but really getting information to everybody whose lives will benefit if they understand what this therapy can do for them when they restore shock-absorbing dystrophin to muscles that desperately need it.

Operator: One moment for our next question. That comes from the line of Tazeen Ahmad with Bank of America. Please proceed.

Tazeen Ahmad: Hi, good afternoon. Thanks for taking my question. I just wanted to clarify with regards to what you are seeing with PMO use, initially, doctors were saying that they wanted to keep the PMOs on board with patients even after the patients receive ELEVIDYS. Is that still what you are seeing, and is that assumption also embedded in the $1.2 to $1.4 billion guidance that you provided? Thanks.

Douglas Ingram: Probably that thesis is probably not fully embedded in the $1.2 to $1.4 billion, but to your interesting point, physicians definitely on whole definitely want their patients to have the full armamentarium of gene therapy and a PMO. We have always taken the view, as you know when you talk to investors about it over and over again over the long years even before we got launched, that may not happen a significant amount of time and the patients may be washed out of the PMOs as a predicate to getting the gene therapy, and there will be significant amount of cannibalization.

I would say, at this point, there is more dual use of PMOs and gene therapy than I at least would have envisioned. And I think there is a real opportunity here for patients to fully benefit. This is a very complicated disease, as we all know, and I think having adjunctive therapies with a gene therapy like a PMO makes a ton of sense, and I think that we might be seeing more, not less, of that over time. Patrick, you might provide more detail on that.

Patrick Moss: Right now, we are seeing a handful of patients that have been treated with ELEVIDYS go back on PMO. It is not materially embedded in our forecast. But it is something, as Doug mentioned, that is an interesting proposition and something that the physicians are contemplating as they think beyond ELEVIDYS.

Tazeen Ahmad: Okay. Thank you. And, Doug, best wishes to you and your family.

Douglas Ingram: Thank you so much, Tazeen.

Operator: Our next question comes from the line of Mitchell Swaroop Kapoor with H.C. Wainwright. Please proceed.

Mitchell Swaroop Kapoor: Thanks so much. And sorry to hear about your family, Doug, and wishing you and your family the best as you navigate this new journey and also your retirement. I wanted to ask on the early trends you are seeing in 2026 for ELEVIDYS so far. Obviously, guiding to flat to down 15% for the quarter, but want to know what you are seeing on new patient starts, time to infusion, payer behavior, infusion center capacity, and if any of these factors or other factors are measurable performance signals that you are tracking in the next quarter or two to hit that $1.4 billion versus the $1.2 billion guidance number?

Douglas Ingram: Patrick, I will send this to you.

Patrick Moss: Yeah. And I caution reading too much into really any single quarter. And I mentioned before, ELEVIDYS is not a product where performance unfolds in this, like, smooth linear quarter-to-quarter way. We are seeing consistent enrollment forms come in. However, it is early. And with our efforts and our messaging around the new data, expanding the field salesforce, and really expanding our footprint, we are expecting those efforts to materialize later in 2026. We do have early green shoots, as I mentioned, from prescribers that have paused in the past. But, again, that time from enrollment form to infusion is still around six months.

Mitchell Swaroop Kapoor: Thank you.

Operator: One moment for our next question. It comes from the line of Mike Oates with Morgan Stanley. Please proceed.

Mike Oates: Good afternoon, and thanks for taking my question. And Doug, let me add my best to you and your family as well. Maybe just a follow-up on DM1 and FSHD data you are expecting to share later this quarter. Could you please clarify what PD data we should be anticipating? From the slides, it looks like maybe splice correction. We should not expect that, but maybe you can clarify what we might get. And then, should we anticipate VYONDYS as well? Thanks.

Douglas Ingram: Sure. I will turn this to Louise.

Dr. Louise Rodino-Klapac: Yep. So in terms of PD for DM1, we will have early DMPK knockdown data, and for FSHD, it will be FSHD DUX4 target gene correction, in terms of the early data for that.

Mike Oates: Great. Thanks.

Operator: Our next question comes from the line of Biren N. Amin with Piper Sandler.

Biren N. Amin: Yeah. Hi, guys. Thanks for taking my questions. And I also wanted to convey my well wishes to you, Doug, and your family. Maybe on the Cohort 8 data, what do you need for FDA to demonstrate safety? I expect it would be, you know, clear for acute liver injury, but would FDA also want to see ALT, AST elevations in the trial? And what bar would be acceptable on ALT, AST elevations? And I guess maybe just a second question would be, can you give us the status of ENVISION and when you would hope to restart that trial? Thanks.

Douglas Ingram: Sure. I will turn this to Louise.

Dr. Louise Rodino-Klapac: Sure. For the Cohort 8, we are certainly collecting all parameters, which include AST and ALT, and that goes into the calculation of ALI in addition to GGT and others. So, certainly, that will be part of the calculation, but that goes into the definition of how we define acute liver injury. So certainly, FDA and us, importantly, will be looking at that. In terms of ENVISION, we expect in the U.S. to first look at some of the Cohort 8 data to help inform restarting that trial.

Operator: Our next question comes from the line of Kostas Biliouris with Oppenheimer. Please proceed.

Kostas Biliouris: Thanks for taking our question. Doug, congratulations on a terrific career and sorry to hear about your family members. You sent a nonevent press release into the most important conference call this year. Maybe one question from us on DM1 given the relevance. We saw recently a publication from Avidity on DM1. And although they saw drug concentration in muscle in a dose response manner, when it comes to splicing correction, the data were very inconsistent and without any trends across placebo and active arms.

Any thoughts on whether this could also happen in your case, if it is a result of variability, and how should we interpret the potential outcome like that if there is muscle concentration but then the biomarkers are not consistent? Thank you.

Douglas Ingram: Sure, Louise. Take that.

Dr. Louise Rodino-Klapac: Without having read that publication, a few things to note. So based on our preclinical data, we see a correlation between muscle concentration and correction. I do believe that there are some limitations with dosing in their case in terms of how high a dose they can get, so that might have played into it. I have not seen the publication. But what I can say from our preclinical data is we do see a correlation with muscle concentration and correction.

Douglas Ingram: Yeah. Also, to me, I may be missing the most recent data, but I was under the impression that at least at the doses that Avidity was capable of dosing to without a dose-limiting toxicity, they did not see enormous differences in muscle concentration. On the other hand, DYN did, but then because DYN’s therapy is a PMO, that additional muscle concentration does not result in significant additional knockdown because of the requirement that you need the machinery inside of the cell to affect the blocking that occurs with the exon-skipping modality of a PMO.

So I may be missing something we need to look at, but at least what we are seeing in our preclinical models is a very clear direct correlation between muscle concentration and the ability to knock down and then downstream splice correction, which, frankly, Occam’s razor for an siRNA would tell you that is what you are going to see.

Kostas Biliouris: Thank you, and congrats again.

Douglas Ingram: Thank you so much.

Operator: Our next question comes from Ritu Subhalaksmi Baral with TD Cowen. Please proceed.

Josh Fleishman: Hi, Doug. This is Josh Fleishman on the line for Ritu. We send our best wishes to you and your family, and thank you for taking our question. How strong has physician and patient interest been in ENDEAVOR Cohort 8 recruitment? Can you give any color on the current extent of enrollment?

Douglas Ingram: Sure. Louise, do you want to touch that?

Dr. Louise Rodino-Klapac: Yeah. Certainly. There is a significant interest in Cohort 8. We are in the process of screening and have not dosed yet. We expect to do that soon, but we are on track, as I mentioned, to present data by the end of this year.

Josh Fleishman: Okay.

Douglas Ingram: Take care.

Operator: Our next question comes from the line of William Pickering with Bernstein. Please proceed.

William Pickering: Hi. Thank you for taking my question. And, Doug, wishing you and your family well. For DM1, could you clarify if the initial disclosure will include Cohorts 3 and 4? And how much follow-up do you think that you need to see a splicing benefit? In the Avidity New England Journal paper, the authors hypothesized that the 1 mg/kg dose did not show a splicing benefit despite good DMPK knockdown because the biopsy was at Day 45 as compared to biopsy at Day 90 for the higher doses that did show a splicing benefit.

So just wondering how you think about the length of follow-up you need to see the splicing improvement and if that informed the plan to wait until second half of the year to share that splicing data.

Douglas Ingram: Louise, do you want to touch on that?

Dr. Louise Rodino-Klapac: Yes. So for DM1, to your point, we will have the SAD cohort data. We will have early data on MAD, which will be primarily safety data for that. In terms of the splicing panel, the CASE 22 for DM1, that will be second half of this year. The DUX4 target gene expression, we will have early data from that in this preliminary readout and then additional data from the MAD cohorts later on in the year.

Operator: Our next question comes from the line of Brian Skorney with Baird. Please proceed.

Luke: Hi, team. This is Luke on for Brian. Thanks, Doug, for your openness on the call, and best wishes for you and your family. We have a broader question on the DM1 indication. Just hoping for some insight on understanding of the importance of numerical splice correction data, just thinking about both clinical impact and the perspective of regulators. Is 20% plus still a reasonable sort of bar just in thinking about the current competitive landscape and how that is shaping up? Thank you.

Douglas Ingram: I am going to turn this again to Louise, who will have some views on it. The one thing to know on some of this is we need to really understand and fully analyze the FDA's perspective on this. We will need to have meetings with the FDA, and I do want to be clear that is not something we have done. But with that said, Louise, thoughts?

Dr. Louise Rodino-Klapac: Yeah. Based on, as I mentioned, we are early on in this, and so we will be analyzing this first cohort of data to look at the correlation of muscle concentration and splice correction, which we will not have for DM1 just now. And so we will be analyzing all of that, working with our KOLs to inform our Phase 3. So it is early for us to commit ourselves to a threshold in terms of what we think will be meaningful for the Phase 3.

Operator: Our next question comes from the line of Gil Joseph Blum with Needham & Company. Please proceed.

Gil Joseph Blum: Good afternoon, everyone, and hope things go well for you, Doug. It is always, you know, it is not great to hear that the people in your family are having issues, especially with an indication like this. The one question that we have is just a clarification as it relates to the LGMD program. Would you need to dose any patients with sirolimus prophylaxis before coming back to that, or is the data from the DMD study sufficient there? Thank you.

Douglas Ingram: So the short answer is we need to have more conversation with the agency about that. There have been suggestions in telephone calls with the agency that they might want to see a patient dosed prophylactically with sirolimus. But, on the other hand, we will have had a significant amount of prophylactic dosing with our DMD therapy, and it is exactly the same asset, so it should be quite relevant. So we will have to have more discussions with the agency. If there is some benefit to, for instance, dosing a patient, this is an ultra-rare disease, so we are not dosing a lot of patients prophylactically as a predicate to a BLA. This is ultra, ultra-rare disease.

But, you know, if we are required to dose a patient, we certainly would do that. But, Louise, if you have more color than that, let me know.

Dr. Louise Rodino-Klapac: No. I just thought that they specifically wanted to see data from Cohort 8 first and subsequent to that, so we will have that conversation once we have data in hand.

Gil Joseph Blum: Thank you, and best wishes again.

Douglas Ingram: Thanks.

Operator: Thank you. Our next question comes from Sami Corwin with William Blair. Please proceed.

Sami Corwin: Hi, thanks for taking my question. And, Doug, sending our best wishes to you and your family as well. Regarding the PMO guidance, I guess I was curious what your internal assumptions are for competition with some emerging exon skippers and how a lack of conversion to full approval could impact that guidance. And then regarding the ENDEAVOR trial, do you plan on sharing what enrollment in Cohort 8 has been completed? Thank you.

Douglas Ingram: Yeah. So this is the second part of that question, and Louise can answer that. On the first one, when we think about competition, I think the only credible near- to mid-term potential competition on the exon skippers is an exon 51 therapy. First of all, the transition from accelerated to traditional, or if there was a lack thereof, has no impact in a very real sense because, remember, if DYN is capable of getting an approval anytime in the near term, it is going to be on the basis of an accelerated approval. So it will be a completely flat playing field with respect to that.

And I think that in the event that they are able to get an accelerated approval, with respect to the PMO side of things, you would think that they might be able to. I think that will be real competition, and I think there will be an interesting play in the marketplace. They will have some features that they will certainly be promoting on their therapy. We have a decade of data on ours to support our therapy, and it is extraordinarily well-tolerated. Families absolutely fiercely are committed to these PMOs. So I think it will be real competition, and we will be selling the benefits of our therapy, and DYN will be selling the benefits of their therapy.

I think that is the real one sort of mid-term potential competitor, and it is only for one of our three PMOs, which is, of course, EXONDYS.

Operator: Thank you. And as a reminder, ladies and gentlemen, if you do have a question, simply press 1-1 on your telephone to get in the queue. Our next question comes from David Hong with Deutsche Bank. Please proceed.

Sean: Yeah. This is Sean on for David. And thank you for taking our questions, and our best wishes to you, Doug, and your family. Just a quick question on the recent announcement of DMD being added to the federal Recommended Uniform Screening Panel. Can you give us a sense of how rapid individual states might be rolling out the recommendation in their newborn screening programs? How that will impact the demand for ELEVIDYS going forward? Thank you.

Douglas Ingram: Yeah. A couple thoughts on that. First, before I talk about the mechanics of it, understand that this is fantastic. We have been working towards this day, and the patient community has been working for this day, for a very long time. So it was a really significant moment to get DMD added to the newborn screen panel.

And I also want to give an enormous amount of credit and kudos to Secretary Kennedy himself who really spearheaded this after consultation with specific folks from the patient community, understanding the significant value of having this out there, particularly so that at the earliest possible date patients can benefit from existing therapies, including, for instance, our PMOs, EXONDYS 51, AMONDYS 45, and VYONDYS 53. That was explicitly discussed with Secretary Kennedy. So I want to give a lot of kudos to HHS for their willingness to do that. On the timing of this, this is going to be a really significant opportunity, but it is not going to be a near-term opportunity.

So do not envision that this is going to have some impact on our guidance this year. For two reasons. One, it takes time. I probably cannot tell you how much time per state. My head of Government Affairs, Diane, would do a much better job than I will of exactly that. But it takes some significant time to roll this out on a state-by-state basis. We have a significant number of states that have newborn screening, but this will, of course, really expand it with it being on the federal RUSP. The second thing to know, remember, at least as it relates specifically to ELEVIDYS, is that ELEVIDYS is for the treatment of boys four years and older.

So to really see the benefit of this for the very young patient, we need to lower that age range. And we are working on that and intend to engage with the FDA and have some discussions about that. We think the data that supports going to a younger age is really compelling. We have got only great expression. We have already proven that our therapy is efficacious. We have proved it over and over again, which is really important, by the way. Let us be very clear.

One of the things that is so heartening about our therapy is that we have so many clinical trials and specifically we have this very large placebo-controlled trial that showed data in one year and two years and three years. Taking all that data and then looking at the safety for very young kids and looking at the expression you get with the very young kids, that is a very compelling argument. But to really fully get the benefit of this, we are going to need to adapt that label, and that will take some time and some discussion. So both of those issues are going to delay the opportunity, but the opportunity is coming.

And it is a really big deal. And, again, it is very easy to criticize, but in this situation, I just want to give enormous kudos to HHS. And I really want to give specific kudos to Secretary Kennedy for his willingness to lead in this area and to focus on trying to create a better life for young boys that have Duchenne muscular dystrophy. And it is important because, as we say over and over and over again, to the point of almost being trite, time is muscle. And at any stage in this disease, if you can get in there and treat, you can save muscle that will otherwise be forever lost.

And that is true of a three-year-old versus a four-year-old or a two-year-old versus a five-year-old just as it is true of a nine-year-old versus a 12-year-old or an 11-year-old versus a 14-year-old. So this is a big deal.

Operator: Our next question comes from the line of Andy Chen with Wolfe Research. Please proceed.

Brandon Richard Frith: Hey. This is Brandon on for Andy. Sorry to hear the unfortunate news, and thank you for taking our question. One from us. On the Japan launch, are there any early signs such as start forms or other signals that give us confidence in a positive launch within that region? Thank you.

Douglas Ingram: Yeah. We really are not in a position to provide that information. I think Roche is a perfect group to provide that information. I am very excited about the launch, but that really comes more from the basic knowledge that Japan has a very sophisticated health care system. It is very large. It has a lot of patients that can benefit from this. And I think our partner Roche and their subsidiary, Chugai, I think will do a brilliant job of serving the community in Japan. So I am excited about it, but I cannot give any more detail than that broad stroke, and I think Roche can probably do a much better job of that than I can.

Brandon Richard Frith: That is all from us. Thank you.

Operator: Thank you. And this concludes our Q&A session. And I will pass it back to Mr. Ingram for closing comments.

Douglas Ingram: Alright. Well, thank you all very much for spending time with us today. I am just going to end with the way I started. 2025, as we all will acknowledge, was a difficult year filled with a lot of unexpected obstacles that needed to be overcome. I am proud of this team for having worked through that and stayed resilient and overcoming them. I am also proud of us taking the decisions we took in 2025 that put us in a strong position.

Everything from the way we worked with the community itself, the fact that we restructured our convertible debt to remove any overhang, and we did a restructuring, painful though it was, really allowed us to focus on the highest-value programs—highest value to the patient community and to Sarepta Therapeutics, Inc.—and I think we are entering 2026 in a really strong place. We are strong financially. We have going on a billion dollars in cash and investments. We will be growing that cash balance over time even as we fully invest in our programs and commercial launch.

We have four therapies that are bringing better life to patients every single day—really very resilient PMOs that people love—as well as ELEVIDYS, where the evidence on ELEVIDYS and its benefits grows quarter to quarter to quarter, and we are going to make sure that everybody that can benefit from that knows it. And I am quite confident that is going to have a big impact first on the lives of those patients and then, with the benefit on those patients, to our investors. And then, finally, we have this extraordinarily exciting siRNA pipeline that includes now Huntington's disease, where we have actually started our clinical trial, and we will be dosing patients starting next quarter, not next year, folks.

And we are dosing DM1. We are dosing FSHD. We are dosing SCA2. We are dosing IPF. We will have a readout on IPF later this year as well. So we have got this extraordinarily impactful pipeline as well, and we have got a team that knows how to execute and make the most of this pipeline, bringing better lives to these patients as well. Over time, I think that we will get the benefit of all of this extraordinary work as well. So thank you very much for your time. We look forward to updating you across the course of this year as well. With that, have a lovely evening.

Operator: And this concludes our conference. Thank you for participating, and you may now disconnect.

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