SRPT

Good afternoon, and welcome to Sarepta's first quarter 2026 earnings results call. As a reminder, today's program is being recorded. I would now like to turn the call over to Tam Thornton, Sarepta's Director of Investor Relations. Please go ahead.

Thank you, Antoine, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2026. The press release, along with our presentation slides and supplementary information, will be 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 today are Doug Ingram, our CEO; Dr. Louise Rodino-Klapac, President of Research and Development 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 Operations Officer, and Dr. James Richardson, our 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.

Please refer to slide 2 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 for 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. 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, Doug Ingram. Doug?

Thank you, Tam Thornton. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' first quarter 2026 financial results conference call. We entered 2026 with a clear set of priorities: stabilize the business, restore confidence and growth, maintain financial strength, and continue advancing a pipeline with the potential to define Sarepta's next era. In the first quarter, we made meaningful progress against each of these priorities. First, our marketed product performance has stabilized following the disruption and uncertainty of 2025 with expanded field reach, increased physician engagement, and a growing body of compelling evidence supporting the disease-modifying impact of ELEVIDYS. We believe that therapy is positioned to return to growth. Second, Sarepta remains in a strong financial position.

We ended the quarter with approximately $748 million in cash and investments, delivered positive GAAP and non-GAAP earnings, generated positive cash flow excluding Arrowhead-related payments, remain on track for positive cash flow even under our base case assumptions. The financial strength matters. It allows us to fund our pipeline without relying on the equity markets. We are fully funding our programs in DM1, FSHD, Huntington's disease, the spinocerebellar ataxias, our preclinical and research portfolio. Third, we are making progress in what we believe is a potentially best-in-class portfolio of siRNA therapies. As Dr. Louise Rodino-Klapac will discuss shortly, we are especially encouraged by the early data from SRP-1001 in FSHD and SRP-1003 in DM1, we look forward to additional readouts in the second half of this year.

Turning to 1st quarter performance, total net product revenue was $331 million. That included $229 million from our PMO therapies, EXONDYS, VYONDYS, AMONDYS, and $102 million from ELEVIDYS. Starting with the PMO franchise, we were pleased that the FDA agreed that we can submit our clinical data and real-world evidence for VYONDYS and AMONDYS. We have submitted sNDAs seeking to transition those therapies from accelerated approval to traditional approval. That is an important step for patients, physicians, and of course, the durability of this franchise. Turning to ELEVIDYS, Patrick will provide more detail on the commercial initiatives underway and the early signs of progress we are seeing. I want to underscore the central point. Our confidence in ELEVIDYS is grounded in evidence, not in mere aspiration.

To date, more than 1,300 patients have been treated with ELEVIDYS across clinical trials and commercial use around the world. The totality of the evidence continues to strengthen. The data show that ELEVIDYS is protecting muscle and changing the trajectory of Duchenne. It is giving boys and young men an opportunity that, until now, this disease has never afforded them. We saw this in EMBARK, the only robust double-blinded placebo-controlled trial demonstrating the benefit of a gene therapy in Duchenne. We saw meaningful benefits at year 1. We saw those benefits grow at year 2, and yet again at year 3. Boys continue to diverge on every measure from the expected course of untreated disease. That matters because Duchenne does not wait. Muscle damage is progressive, irreversible, and cumulative. Every month of delay risks further loss.

The evidence increasingly supports a simple but urgent message. Physicians and families should evaluate ELEVIDYS now before additional irreversible damage occurs. We have also seen supportive muscle MRI evidence showing that ELEVIDYS dystrophin helps protect muscle from damage, resulting in less muscle loss and less replacement by fat and fibrotic tissue. This is exactly the kind of biological evidence one would hope to see from a therapy intended to alter the course of Duchenne. We are confident that as physicians and families better understand the disease-modifying potential of ELEVIDYS and the urgency of intervening before further decline, more patients will move towards treatment. That said, we are still in the middle of our commercial and educational initiatives. The path from consideration to infusion takes time.

For that reason, we are reiterating our full year guidance of $1.2 billion-$1.4 billion and would counsel prudence in raising estimates prematurely. Staying with ELEVIDYS, we are also advancing our ENDEAVOR Cohort 8 study, which uses sirolimus as a pretreatment. More than 25% of sites are already using sirolimus on their own initiative. In our interim analysis from the long-term real-world evidence study that we have ongoing, patients pretreated with sirolimus have shown no evidence of elevated liver enzyme to date. That gives us further confidence in Cohort 8 and in the potential with the success of that study and the concurrence of the FDA to resume offering ELEVIDYS to non-ambulatory patients. Turning to the pipeline, our focus is execution. We are rapidly advancing our siRNA portfolio, including our DM1 and FSHD programs.

The first data readout earlier this year showed encouraging signals that these may be differentiated, potentially best-in-class approaches for two very challenging diseases. We look forward to providing additional data later this year. We have initiated and are on track to dose our first patients in our Huntington's disease program, and we are progressing clinical trials in SCA2 and idiopathic pulmonary fibrosis. To summarize, the business is stabilized. ELEVIDYS is supported by an increasingly compelling body of evidence. Our financial position is strong. Our high-value siRNA pipeline is advancing across multiple programs. We believe Sarepta is well-positioned in 2026 and beyond. With that, let me turn the call over to Louise, who will provide an update on our siRNA portfolio and broader development progress. Louise?

Thanks, Doug, good afternoon, everyone. Our diverse and advancing rare disease portfolio has always been driven by a core fundamental truth: pursue the very best science and then follow where it leads. In March of this year, we announced positive preliminary data from our lead programs to treat FSHD and DM1, which are based on the potential of our alpha-v beta-6 integrin-targeting ligand to produce best-in-class therapies in these unmet disease areas. Importantly, our integrin receptors are highly expressed in muscle in addition to other tissues. They are also actively trafficked between the cell surface and endosomal compartments through relatively well-understood pathways. Non-clinical data show that targeting these integrin receptors via small peptides leads to enhanced skeletal muscle uptake compared to using a much larger TfR1 antibody.

It's also important to note that based on data to date, our alpha-v beta-6 integrin-targeting ligand provides superior muscle concentration compared to transferrin-based approaches without dose-limiting toxicity. I will now summarize the early data from our FSHD and DM1 programs. SRP-1001 is an siRNA-based treatment designed to reduce or knock down the production of DUX4 protein in skeletal muscle in patients living with FSHD1. Study 1001-101 is our combined phase I/II single ascending dose and multiple ascending dose randomized placebo-controlled trial in participants with FSHD1 aged 16 through 70.

As previously shared, we believe our preliminary data from the phase I/II SAD study supports the potentially differentiated attributes of SRP-1001, including a dose-dependent increase in plasma exposure up to the highest dose cohort, also superior delivery to muscle enabled by a differentiated approach with the alpha-v beta-6 integrin, including no saturation of drug uptake, significant suppression of DUX4-related genes, and a rapid and robust reduction in CK to support functional impact. Finally, a favorable safety and tolerability profile with repeated dosing, including no indication of anemia, which physicians have indicated represent an important therapeutic advantage.

We look forward to sharing results from the MAD portion of this study later in the year, which we expect will include at least 6 months of follow-up for our 6 and 12 mg per kg MAD cohorts, which is equivalent to 4 and 8 mg per kg siRNA dosing. This is with respect to safety PK/PD data, including circulating biomarkers and DUX4 related regulated genes as well as early functional data. We also plan to discuss our post phase II with FDA to define an optimal registrational pathway. Moving to DM1. SRP-1003 is an siRNA-based treatment for DM1 designed to target or knock down or silence the DMPK mRNA in target cells. Study SRP-1003-101 is a first-in-human phase I/II SAD/MAD randomized placebo-controlled clinical trial being conducted in individuals with DM1 aged 18 to 65.

The early data we generated for DM1 is important for two reasons. First, our preclinical models are predictive of what we would see 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 demonstrated DMPK knockdown we observed was impressive and directionally strong. As you're aware, DM1 is driven by an expanded CUG trinucleotide repeat in DMPK transcripts, causing mutant DMPK mRNA to accumulate in the nucleus and disrupt RNA splicing. As a result, for any therapy to be therapeutically effective, it must effectively target and knock down or silence DMPK in the target cell. SRP-1003 is being developed to achieve exactly that.

We look forward to sharing these results in the additional SAD and MAD cohorts in this study later in the year, which we expect will include multiple doses measuring mechanistic and functional endpoints with at least 6 months of follow-up for our 6 mg per kg cohort, which is equivalent to 4 mg per kg siRNA. Specifically, we expect to share safety, serum and muscle PK, DMPK knockdown, CASI-22 splicing indices, and VHA-T analyses. We will plan our IND submission for U.S. study shortly after completing our MAD study. We believe these trials, if successful, will support and provide a clear path to support registration. In summary, enhanced muscle delivery, robust target engagement, and maximal knockdown are well recognized as the gold standard for FSHD and DM1, and we're excited by the potential of our therapies to reach this standard.

In terms of our other siRNA pipeline program, we are on track for first patient in for Huntington's, and our SCA2 trial is fully enrolled. We look forward to sharing data as it becomes available. Turning to ELEVIDYS. We are pleased to announce in March that screening and enrollment are underway in cohort 8 of ENDEAVOR or 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 non-ambulant 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, a known risk associated with AAV gene therapy. The cohort is enrolling approximately 25 participants in the United States who are non-ambulatory and dosing is currently underway.

As a reminder, the immunosuppression regimen will include 14 days of peri-infusion sirolimus dosing 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. The approach is based on preclinical data and shaped by real-world clinical experience, including guidance from independent specialists in Duchenne and liver health. As Doug mentioned, in addition to EMBARK 3-year functional data, we also reported at MDA caregiver-reported impressions from EMBARK through 2 years of follow-up, offering complimentary perspectives on treatment impact beyond clinician-reported and performance-based outcomes. We are pleased that our body of evidence for ELEVIDYS continues to grow with an unprecedented number of patients dosed, as well as the years of follow-up. We remain steadfast in our commitment to serve the Duchenne community by generating clinical and real-world data to support understanding of long-term outcomes.

This also includes our phase IV observational study, ENDURE. Moving to AMONDYS 45 and VYONDYS 53. In March, we announced that we requested a meeting with FDA to discuss submitting supplemental new drug applications or sNDAs, seeking conversion of the accelerated approval of AMONDYS 45 and VYONDYS 53 to traditional approvals. This request was supported by data from the ESSENCE confirmatory study, substantial published real-world evidence supporting treatment, and the favorable safety profiles of both therapies. Director received feedback from the agency confirming that we were clear to submit our data from ESSENCE and real world evidence as part of the sNDAs. We are pleased to share that we successfully submitted our sNDAs at the end of April. In summary, we have numerous value-building milestones upcoming across our Duchenne and siRNA portfolio.

Thank you, and I'll now turn the call over to Patrick for an update on our commercial performance. Patrick?

Thank you, Louise, and good afternoon. Today, I'll summarize our performance in the first quarter for our on-market therapies, provide an update on execution of our 2026 initiatives, and close with how that translates into performance for second quarter and the balance of the year. For the first quarter, total product revenue was $331 million, including net product revenue of $102 million for ELEVIDYS and $229 million for the PMOs. For ELEVIDYS, first quarter results reflected measured demand, which we believe was influenced by the ongoing information gap within the ambulatory population. This reflects the dynamics we outlined last quarter as we advance efforts to rebalance the discussion around safety and efficacy to support informed decision-making for ELEVIDYS treatment. Importantly, Q1 demand fundamentals have not deteriorated.

Instead, we are addressing the information gap we know exists and are building momentum around a robust label and new data following the events of 2025. The PMO franchise continued to demonstrate durability with demand remaining stable and in line with expectations for mature therapies that are foundational for slowing the decline of Duchenne. We experienced seasonal dynamics in Q1, which contributed to the quarter-over-quarter decrease versus Q4. Our focus for 2026 and beyond remains squarely on ensuring that patients and physicians have a balanced, data-driven understanding of ELEVIDYS's benefit risk profile. The treatment journey for ELEVIDYS has multiple touch points, including patient identification, referral, evaluation, and payer review, in addition to the time and information a family needs when deciding to pursue treatment.

While our commercial model supports all the touch points within this treatment journey, as discussed last quarter, we are actively implementing a number of initiatives to augment our execution, including expanding the number of field resources to support referring physicians, extending our reach within sites of care. The company is deploying new educational resources and tools to support patients and families. We have increased our footprint fielding a contract sales force to focus on physicians who may be in a position to refer patients to a site of care for gene therapy or prescribe one of our exon-skipping therapies. This team recently completed training and deployment in the field is underway. We expect the team to be fully operational as we enter the second half of this year.

Expanding our footprint with a contract sales force has enabled us to deepen our efforts at sites of care with our Sarepta sales team. Our sales team will devote time to more robust interactions with prescribers at sites of care and engage with the extended care team. In addition to my team's initiatives, the company is developing more educational resources and tools to aid patients and families in their preparation for a conversation with their clinician. In an age where information online is abundant and can be difficult to navigate, having clear resources and tools available to caregivers and patients is Sarepta's response to supporting the unique and very personal journey of each patient. All these interactions with referring clinicians, prescribers, supportive care providers, families, and caregivers are grounded in clarity, repetition, and transparency as we recognize the decision to treat with ELEVIDYS requires time and trust.

To date, a growing body of empirical evidence supports that ELEVIDYS is changing the trajectory at Duchenne. We integrated the long-term EMBARK data, including muscle MRI findings, into our educational efforts and discussions with clinicians addressing what matters most: preservation of muscle over time. Our efforts are having an impact, feedback from prescribers and the patient advocacy community affirms our approach. Safety must be considered within the totality of evidence, including the durable benefit of ELEVIDYS. HCPs and the ambulatory population were directly affected by misperceptions of ELEVIDYS, education remains essential and is a focal point of our work. We remain confident that all these initiatives should address the needs of prescribers and patients. I do want to set expectations very clearly. The time from enrollment form to infusion is a 6-month process.

Given this, it will take time to see the potential impact of my team's action to be reflected in sales. Last quarter, I said we are seeing green shoots, early signals that give us confidence we are headed in the right direction. The team is squarely focused on delivering the efficacy message to derive demand. For example, enrollment form activity is more geographically diverse. Sites have previously paused activity in 2025 are participating and submitting enrollment forms. Across the broader referral ecosystem, we are seeing more consistent HCP engagement, suggesting that awareness and understanding of the benefits of ELEVIDYS is resonating. We expect momentum to build progressively through 2026, with greater visibility into improvement most likely to emerge in the latter part of this year and into 2027.

Our efforts are substantive in responding to the needs of prescribers and patients and will improve with reach and repetition. Reestablishing momentum will lead to steady growth over time and not a sharp inflection. We believe our guidance assumptions for 2026 appropriately reflect a measured trajectory accounting both for timing dynamics and patient decision cycles. Given this reality, we are comfortable with the Q2 consensus. As Doug stated earlier, we reiterate the full year guidance of $1.2 billion-$1.4 billion and would counsel prudence in raising estimates prematurely. Our long-term conviction in ELEVIDYS remains strong. As the only FDA-approved gene therapy for Duchenne muscular dystrophy, we have treated more than 1,300 patients in both the clinical and commercial settings with ELEVIDYS. The current and growing body of data demonstrates the disease-modifying potential of ELEVIDYS.

As a result, we believe ELEVIDYS has the opportunity to remain a cornerstone therapy in Duchenne for years to come. Finally, a brief update on the PMO franchise. The PMO franchise remains durable in 2026, supported by long-standing physician experience, a well-understood safety profile, a continued commitment to preserving muscle function, and exceptionally high rates of adherence with our therapies. Physicians continue to view exon-skipping as an important treatment, particularly for patients who are not candidates for gene therapy or for those who choose to defer treatment. The robust body of real-world evidence that demonstrates meaningful benefits in survival and cardiac function reflects more than a decade-long commitment of Sarepta's scientific investment and leadership dedicated to improving outcomes for those with Duchenne. In closing, our commercial focus in 2026 is clear.

Execute with discipline, educate with data-driven conversations, build momentum, and support the unique needs of each and every patient. We are encouraged by the early rebuilding signals for ELEVIDYS, the stability of our PMO business, and the long-term opportunity to support those with Duchenne and change the trajectory of the disease. Thank you, and I'll turn the call over to Ryan. Ryan?

Thank you, Patrick, and good afternoon, everyone. On behalf of the Sarepta team, I'm pleased to report a strong quarter of financial execution to start the year, where our base business was profitable and cash flow positive. In my brief remarks today, I'll share highlights from the quarter and some perspective on how we're thinking about the rest of 2026. Starting with the P&L, first quarter total revenues were $731 million, a decrease of 2% compared to Q1 of last year. The decrease in our net product revenues year-over-year was driven by lower ELEVIDYS sales and was partially offset by an increase in collaboration and other revenues.

In Q1, we reported $400 million of collaboration and other revenues, and consistent with previous guidance, this included $325 million of non-cash collaboration revenue related to Roche declining a program option, as well as $40 million of milestone revenue from the first commercial sale of ELEVIDYS in Japan. Turning to gross margin, total cost of sales for the quarter was $109 million, a decrease of 21% compared to last year, driven primarily by lower sales volume. On a unit sales basis, gross margins were 82%. Moving now to OPEX. Combined R&D and SG&A expenses in the first quarter were $263 million and $224 million on a GAAP and a non-GAAP basis, respectively. Both included the $50 million annual Arrowhead collaboration license fee recorded to R&D.

This was a significant decrease compared to the prior year quarter because of the cost restructuring initiatives enacted last summer and as the prior year quarter included the upfront transaction cost from the Arrowhead collaboration. Putting it all together, in the first quarter, we delivered a GAAP operating profit of $358 million and a non-GAAP operating profit of $398 million. These results are reflective of the strength of our underlying business and the non-cash collaboration revenue recognized during the period. Shifting to the balance sheet, we ended the first quarter with $748 million of cash and investment, a sequential decrease of $206 million, driven by $250 million of payments to Arrowhead for the second DM1 milestone and the annual collaboration payment I just mentioned.

As noted earlier, excluding these planned payments, our base business continued to generate positive cash flow. Looking ahead to the remainder of the year, we are reaffirming our prior revenue and OPEX guidance as well as our expectation of profitability and to be growing our cash balance from here. As you heard earlier on the call, we are very encouraged by the early data emerging from our FSHD and DM1 programs. If the data continue to translate clinically as they have so far, we believe they represent significant opportunities to benefit patients with unmet needs and create long-term value for investors. In closing, I will highlight that our current operating expense outlook and medium-term planning fully contemplate enhancing both programs through a late stage of development.

Leveraging the strength and durability of our commercial execution, we believe we are uniquely positioned to fund and execute these programs and our broader pipeline responsibly without placing strain on the balance sheet. With that, I'll turn the call back to Doug. Doug?

Thanks, Ryan. Let's open the call for questions.

Thank you. At this time, we'll conduct a question and answer session. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we ask that you please limit yourself to one question each. Our first question comes from Anupam Rama from JPMorgan. Please go ahead.

Hey, guys. This is Joy Sohn for Anupam. Thanks so much for taking our question. With your sales force expansion and ongoing initiatives to help close some of these information gaps, I was just wondering if you could comment on feedback you've been receiving regarding your 3-year EMBARK data and which parts of this data specifically have been especially resonating with physicians. Thanks so much.

I'll turn this over to Patrick briefly. You can sort of comment on some of the advisory boards you've had and some of the direct interactions you've had with physicians on the three-year data and other data.

Yeah. Thanks, Doug. We've been having multiple ad boards and discussions with physicians, both myself and Ian and Doug one-on-one, but also the field team as they're out there engaging. What's moving the needle is the efficacy data, as well as the MRI data. Once the physicians see both, the divergence over time from natural history of patients that are treated with ELEVIDYS tied down with the MRI data, that's moving the needle and also reflects exactly what they were expecting from a therapy like ELEVIDYS, as well as what they're seeing in their clinic.

Well, I think all that's exactly right. You had more experience with it even than I have. You know, there are a couple reasons that this is occurring. The first is the data itself is really impressive. If you look at the one-year EMBARK data on every secondary measure, every climb measure, we were statistically significant on this placebo-controlled and blinded, well-controlled study. You look at 2 years on all measures. We are doing much better. ELEVIDYS is doing much better than untreated patients, and that gap grows even more in year 3. Exactly what you'd expect from a disease-modifying therapy that's changing the trajectory of disease.

From an urgency perspective, we have muscle MRI data, which is exactly what you would expect to see, which is that if you get treated, you are going to save yourself from a lot of damage and the fat and fibrotic tissue that comes from that damage and the loss of muscle. So it's understandable that it's compelling when you talk to physicians about all of this data. That's not even all the data that we have. We obviously have the 5-year data from our original cohort as well. The other thing that's important to understand when you think about our initiatives is something that is both frustrating but in a big opportunity, which is when you do market research, what I've just told you now and what Patrick's mentioned to you now is not well understood.

That in large measure because of a lot of the important things that happened last year, but that distracted us last year, there was a lot of focus away from what this therapy was doing for patients. As we sit here right now, both in the patient community and significantly in the physician community, there is a massive information gap around those issues. When you sort of take that and kinda shake off the frustration that comes from that and realize that's actual opportunity, you think about the initiatives that Patrick's putting in place, gives us an enormous amount of confidence for the future. We've more than doubled the size of our sales force. We have a contract sales force. We have crammed data now. We have much better promotional material founded on that great data.

We have great educational efforts in the patient community and the, and the like. We have the muscle MRI data that makes the point that you cannot wait, that you will never catch up if you wait. There's an enormous amount of opportunity here to benefit patients and to get ELEVIDYS moving. With that said, I'm gonna say what I said in my script, and I do wanna be very careful. We are excited about where we are. We have these initiatives that are in play. This is a long cycle process, and you know, we're reiterating our guidance, $1.2 billion-$1.4 billion, and we'd ask you along with us to exercise some prudence in changing estimates until we get these initiatives going along the way.

The good news is that we're in a great place, even in a base case situation, to fully fund without the need to go to the equity markets, what is a very, very exciting siRNA pipeline.

Thank you. Our next question comes from Kostas Biliouris from Oppenheimer. Please go ahead.

Thank you so much for taking the question. One question on AMONDYS and VYONDYS sNDA, and sorry if I missed it. Can you clarify whether you have requested or received priority review there? And when should we expect a decision from the FDA? Thank you.

Yeah. This is, these are sNDA. We didn't ask for priority review, so it's the regular time cycle. We would imagine that the PDUFA date will be sometime in February of next year.

Thanks.

Thank you. Our next question comes from Eliana Merle from Barclays. Please go ahead.

Hey, guys. Just two questions from me. You mentioned some 1Q seasonal dynamics. Can you just elaborate on what you saw there and how we should think about the appropriate run rate as we head into 2Q and beyond for both the PMO franchise and ELEVIDYS? A question on the Huntington's program. Can you walk us through what you see as potentially differentiating versus other silencing approaches in development and what we could expect from the proof of biology data next year? Thanks.

Sure. I'll turn the first part of the call over to Patrick, after which Louise can touch on the Huntington's program.

Yeah. What we do know and what we do see is quarter-to-quarter dynamics. They're noisy, right? It reflects just a small number of patients, either this quarter or the next quarter. When we look at it's not, you know, something we can be extremely precise on. We do know things like illnesses, you know, patient family dynamics do impact those quarterly dynamics. That's something that, you know, we do look at and evaluate as we provide our guidance.

Yeah. One thing I will say about that as well is, remember, the reason for all of that is that this is a one-time therapy. You know, with a chronic therapy, you kind of get this installed base, and you're really just forecasting on the margin. With a one-time therapy, you're forecasting new every quarter. With a therapy with like ELEVIDYS, which is a couple of million dollars net, a couple patients that have the flu in the last week of the quarter can impact. There's just a little more variability here. As much as we have a nice line of sight, there's more variability here than you might see in a chronic therapy.

On the PMO side, with there's lumpiness in the ex-U.S. business as well. At the beginning of the year, we do see insurance changes. That does impact the PMO side of the ledger.

With that, we will turn the call to Louise.

Thank you. As you mentioned, we're very excited about the Huntington's program, and we think that we are potentially differentiating for several reasons. The first is really the use of the mechanism of action, and that's using the TFR ligand in combination with the subcutaneous injection. This really allows us, based on preclinical data, to get into the deep brain regions, which is essential for Huntington's disease like the striatum. Based on the preclinical data in mouse models as well as non-human primates, we have particularly high knockdown in these deep regions, and that's really what set this program apart for us and got us excited. It's early days.

We are on track for first patient in. We will be looking for proof of biology, in terms of safety and then evidence of activity in terms of knockdown, in the first data that we see, and that'll be earlier next year. I'm very excited based on preclinical data and very much looking for differentiation based on the mechanisms of action and the dosing itself, which is much less invasive than some other programs.

Thank you. Our next question comes from Andrew Tsai from Jefferies. Please go ahead.

Hey, congrats on the quarter. This is Matt Barchas on for Andrew Tsai. I just wanted to ask about what you guys are expecting in terms of the reduction of ALI incidence in the non-ambulatory cohort 8 from this dataset expected later this year. I think you said you wanted to see a 50% reduction in ALI rates, where I think the clinical rate is around 40%, but is it different in the real world? Might ALI rates in cohort 8 actually mimic the real world setting?

I'm gonna turn this question over to Louise, but before I do, let me make a quick comment, which is that we do have some evidence for cohort 8 that gives us some confidence around the success of cohort 8. Dr. Sossahlo, as you may know, has pre-treated a number of patients and presented that data, I believe, at World Muscle earlier this year. In that setting, the pretreatment with sirolimus completely abated any increase in liver enzymes. Also, we have the real world evidence study, ENDEAVOR, I believe, and we've done an interim analysis there. Early days, I wanna be very clear, the overlapping evidence 'cause some of Dr. Sossahlo's data is in there as well.

In that setting as well, we've seen no increases in liver enzymes so far when a patient is pre-treated with sirolimus. Obviously, we need to dose more patients. Obviously, we need to get cohort A dosed and get the readout on there. As you can imagine, given that, given our preclinical data, and given the experience anecdotally from other physicians who've used sirolimus in other immunosuppression regimens, we feel a significant amount of conviction around the potential success of cohort A, the ability to get back to offering this therapy to non-ambulatory patients who desperately need a therapeutic option, would have none but for this therapy. With that, I'll turn it over to Louise to talk about the clinical trial itself and what the standards are there pursuant to the stat plan.

Sure. You are correct. We are looking for a 50% reduction in the incidence of ALI. The trial is an open label trial that's enrolling approximately 25 patients. We do have the ability to look at the data and enhance the end if required. Regarding the ability to reach that 50%, I'm going to ask Dr. Richardson to just comment on it in the clinical trial versus the real world.

Yeah. Thank you, Louise and Anya. Yeah. Thank you, Louise. And you're quite right that we have seen a different instance of ALI in the clinical trial setting versus the real world setting. That's partly driven by the use of the research as a GLDH in the clinical trial setting. We'll be using it in cohort A. Our primary analysis will be to look at a reduction of 50% or more versus our historical clinical trial rates, which include GLDH. We'll also be able to look at it without GLDH to make sure that there is no specific signal to that biomarker. As Louise says, as an open label study, should we see anything that deviates from these original assumptions, we'll be able to adjust the sample size accordingly.

Thank you. Our next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

Hi, guys. This is Kevin on for Brian. Thank you for taking our questions. Maybe following up on the sirolimus study. Can you talk a bit about your new N of 20 phase IV enhanced study of patients receiving ELEVIDYS and sirolimus in the real world? Just curious how that fits with your potential regulatory strategy for non-ambulatory patients, whether maybe it was required by regulators, and just your considerations on, you know, potentially just simply upsizing the current study versus running this real world study in parallel as well. Thank you.

Well, that, Louise.

Yeah. I'm gonna turn this to James in a minute, at a highest level, the phase IV study gives us the ability to look at the use of sirolimus in ambulatory patients as well, as well as looking at gene expression based on this. These two elements are important to looking at sirolimus in a population other than the non-ambulatory population. James, maybe you can give a few more details about the study.

Yes, sure. Absolutely. I mean, this is a study looking at commercially dosed patients under the same sirolimus regimen as we're using in cohort A. It's not part of a broader regulatory strategy, but simply just asking the hypothesis about the use of sirolimus and its mitigation of ALI in a broader Duchenne population. The data could be supportive to cohort A, but is not necessary for that non-ambulatory strategy. We'll simply reaffirm the current sort of hypothesis that sirolimus is equally well tolerated across a broad range of Duchenne patients than we would expect a similar efficacy in terms of reduction of ALI.

Our next question comes from Michael Ulz from Morgan Stanley. Please go ahead.

Hi, it's Avi Novak on the line for Mike. Thank you for taking our questions. I guess just a quick one on guidance. I think on the prior call you indicated that you're more comfortable with the low end of guidance, so that would be more likely. I guess, given the positive green shoots you've seen early this year, I guess, would you be more comfortable that maybe the middle or high end of guidance might be more likely? I guess if not, what do you need to see to sort of get there? Thanks.

Yeah, thanks for your question. You're exactly right. We guided $1.2-$1.4 and sort of revised folks that they should be thinking toward the lower end of the $1.2-$1.4 until we see more. The short answer is that we are making very good progress in our initiatives, but the initiatives are long cycle initiatives. A number of them have already gone underway. As an example, our sales force is doubled, and they're out in the field talking to physicians, and that's great. We've got great marketing material. We have additional marketing material coming out with our 3-year data as well. That's going to be great. We've got educational efforts.

We got a contract sales force that'll be getting in the field very, very shortly and has been trained up. With all of that said, as, you know, as excited we are and the conviction we have about these tools, we wanna speak cautiously for the time being and just be thoughtful. We're not changing our guidance, and we would caution others to be prudent in raising their internal estimates prematurely. Let's get underway and get these initiatives going. We do see some green shoots, and we certainly see when we, you know, qualitatively when this information is understood by physicians and understood by patients, it has a meaningful impact.

It's going to take some time because these are all, you know, long cycle, essentially, resetting people and getting them to really understand the evidence set, both on safety and efficacy.

All right. Great. Thank you for taking our question.

Thank you.

Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Thanks for taking our question. This is Tommy on for Salveen. Maybe if we could get to a sense that you're available the details on patient numbers at dose levels for the siRNA data by year-end. Especially how will the functional measures for this data factor into how you're thinking about the registrational outlook and kind of competitive comparisons? Thank you.

Great. I'll turn this to Louise.

Sure. Just for both studies. For FSHD, we will have data from our 6 and 12 mg per kg MAD cohorts. Those are our highest dose cohorts. It's equivalent to 4 and 8 mg per kg siRNA. With respect to DM1, we will have our follow-up from our 6 mg per kg MAD cohort, which is equivalent to 4 mg per kg siRNA. As I mentioned, we'll be looking at safety, biomarkers, and early evidence of functional outcomes. James, perhaps you can comment on how we're thinking about the functional data as it's early in terms of the follow-up and the number of patient numbers.

Thank you, Louise. I mean, I think primarily as you say, safety and the PD biomarkers will help us select the appropriate dose to carry forward into the phase III program. Clearly, we're gonna look at the functional data to understand what we think is supposed to be the most responsive outcome that help us select our and drive our design for our phase III. I would not, as Louise has said, expect any significant movement in the functional measures at 6 months in FSHD. In DM1, we would expect to see a signal in vHOT at this timeframe, similarly for the other time function tests, it's very early in this disease state and in the size of cohorts to make any definitive conclusions.

Thank you. Our next question comes from Tazeen Ahmad from Bank of America. Please go ahead.

Hi, guys. Thank you so much for taking my questions. A couple on FSHD and DM1, or rather one on those. How do you think about comparing the data that you've presented so far to products that have already shown data that might be, you know, further ahead in development? Specifically, how should we be thinking about what the right endpoints should be in order to look at? I know that there's a Novartis study that's being debated as to whether or not in DM1 the right endpoint is being used. I'd love to hear your thoughts on that. Secondly, as you talk to FDA about the shift to get the PMOs to permanent approval, can you talk about if there's been any change, any further change in who you talk to in the divisions that are relevant?

Just trying to get a sense of continuity of people that you might be engaging with. Thanks.

Yeah. I'll turn this over to Louise.

Sure. Regarding the comparative data, as we've, as we mentioned in the disclosure call, in terms of what we're looking at and why we think that our program is differentiated in terms of the amount of siRNA that we're getting into the muscle, and that's using the alpha-v beta-6 targeting ligand. That truly in terms of comparison allows us, the more you can get into the muscle, the more knockdown you can get, and that leads to better biomarkers and downstream functional markers. That's the way we're thinking about it with this early data is how can we get the highest level into the muscle so that we can have the most robust effect.

We wanna make sure that we are having a product that is giving us the best chance of efficacy and consequent function. With regards to functional outcomes, I'm gonna turn that to Dr. Richardson in a second regarding DM1. On the PMOs, we're generally interacting with the same individuals in the agency that we have been for the PMO programs and for those NDAs. James, perhaps you can comment on the DM1 function.

Yeah, I mean, I think we're seeing in the DM1 space what you commonly see, as developers move into a disease space that we see an evolution in our understanding of the functional endpoints, and we also see a greater investment in natural history data. We've seen recently with Nicholas Johnson's group publishing from the DM1 study, which is building on our understanding of the appropriate functional outcomes.

I think from our point of view as a sponsor, without commenting other sponsors' program, we're at, you know, at an advantage position of being able to take these natural history data internally, be able to speak to people like Nick Johnson and others and take their opinion on the, on the primary endpoints, and then look at the functional data coming out of the cohorts we're seeing in phase I and II, put that together and reach our own decision on what we think is the most appropriate primary and secondary endpoints for our phase III study, and obviously discuss that subsequently with the FDA.

Thank you. Our next question comes from Joe Schwartz from Leerink Partners. Please go ahead.

Thanks very much. I have a question on the siRNA programs, which we'll have data on later this year. First, is there any data, preclinical or otherwise, which suggests that deeper reductions in DUX4 expression would be expected to translate into greater clinical benefits for your approach in FSHD compared to competitor therapies with lower knockdown p-profiles? In DM1, what specific magnitude of splicing correction would you wanna see in the upcoming MAD cohorts to prove that 1003's differentiated delivery can translate into a best-in-class clinical profile? Why wouldn't VHA-T improve fairly quickly for your approach, since it has seemed to be fairly sensitive for other RNA approaches early on?

I'll turn this to Louise. I will note that I think James did suggest that VHA-T may be an appropriate measure at in the MAD, but that the other longer-term functional endpoints require more time with the disease. With that, I'll just turn to Louise to answer both of those questions.

Sure. On FSHD and the knockdown of DUX4. If you'll recall, DUX4 shouldn't be expressed at this time in late development. It's expressed early in development, then turned off. It should not be expressed in adults. Any stochastic expression is toxic, and so therefore, the greatest amount of knockdown gives you the greatest amount of benefit. If 100% knockdown would be fantastic. Obviously more knockdown is better, and that's what we're looking for. In terms of the target for DMPK knockdown, the answer is similar in terms of what we're looking for. We're looking for increases in muscle concentration leading to improvement in DMPK knockdown. We know that increased from preclinical data, correlation of DMPK knockdown correlates with functional improvement.

That's what we are looking for. Based on the data to date, we've seen dose-dependent increase in muscle concentration. We'll be looking at the DMPK knockdown with our MAD data later in the year. As Doug already mentioned on the VHA-T, we certainly would expect earlier signals as you said for VHA-T as an early sign of function. James, anything to add to that?

No, just completely agree. Just to distinguish between VHA-T, as we said, which we do think we will see a signal with at this point and other functional outcomes which will take longer.

Thank you.

Thank you. As a reminder, to ask a question, we ask that you please press star one one on your telephone and wait for your name to be announced. In the interest of time, we ask that you please limit yourself to one question. Our next question comes from Yigal Nochomovitz from Citigroup. Please go ahead.

Hi. Great. Thank you for taking the questions. I had a question on SRP-1001 and the dose response with respect to muscle concentration. When you doubled the dose, you got about a 6-fold super linear increase in muscle concentration. I'd just be curious if you could comment on that in terms of the mechanistic rationale and whether in the multiple ascending dose part of the study, you would also expect that kind of far exceeding linear dose proportionality at the higher doses. Thanks.

Louise?

Yeah. We certainly saw an increase there which wasn't linear. We would expect to see it start to plateau based on the preclinical data. We did see a jump from the lowest dose, which wasn't un-unexpected based on the preclinical data. We would see it plateau at the higher doses, but certainly continue to increase based on the preclinical data.

Okay. Just one follow-up. With regard to the study that you mentioned, for sirolimus in the real world where you didn't see any evidence of liver enzyme elevations, could you just expand on that in the sense that where there were no grade 1 or any abnormalities in liver enzymes in that real-world study?

Sure. Louise?

Yeah. This is our real-world data where we can go back and survey the results from investigators, and this is an investigator called in terms of ALI. We see that 25% are using it, and we're not seeing any evidence of ALI as determined by the investigator.

Yeah. Thank you.

Thank you. Our next question comes from Ritu Baral from TD Cowen. Please go ahead.

Hi, team. This is Joshua Fleischman on for Ritu. Thanks for taking our question. I wanted to start by asking, what is the current progress of cohort 8 recruitment, and are there any current timelines to enrollment completion? On the call, you guys also mentioned DM1 functional data, but what FSHD functional data will be included in the second half 2026 data release? Lastly, what are Sarepta's plans for additional BD deals, thinking about both timelines to a deal and potential disease areas? Thank you.

Like on cohort 8, I'll just be quick on it and then turn the FSHD question to Louise. I'll touch on the BD. First on cohort A, just so we're clear, we are right where we said we would be. We're dosing patients now, and our goal is to have the study complete and the data available by the end of the year. That we're on track for that. With respect to business development, you know, the good news is that we're in a great place as an organization. We are not required to do business development for our future success. We have a very straightforward strategy right now. We've stabilized the business. We have four approved therapies. They are performing well, and we think they'll perform as it relates to ELEVIDYS even better with our new initiatives.

In a very strong financial position as an organization. We saw that we were profitable on a GAAP and non-GAAP basis, absent our Arrowhead payments. We were cash flow positive. We'll be cash flow positive going forward, even in our base case assumption. That allows us to fully fund our siRNA pipeline, and we're really excited about this siRNA pipeline. You've seen the DM1 and FSHD data, early though it is, and we're excited to see that data later this year. We have Huntington's disease and IPF and multiple SCAs and six research programs, we're in great shape there. With that said, we have a very active search and evaluation group that looks for transactions, we'll continue that. We've got a very proactive head of business development in Joe Zenkus, we're constantly looking for opportunities.

You know, we also have a very high bar for that. That's where we are with that. With that, I will turn the FSHD question to Louise.

Sure. The question was, what functional outcomes are we looking for in FSHD? James, do you wanna comment?

Yeah, absolutely. I mean, I guess to reiterate, the primary purpose of this study is to assess safety, PK, and then the PD response. I think we're particularly excited about also looking at circulating biomarkers at this point. We are obviously conducting functional assessments as part of the study, including reachable workspace, standard battery of time function tests, and strength testing that you would expect. This is a slowly progressive neuromuscular disease. This is, you know, not a point in time where I would expect a very strong signal from a functional endpoint perspective. Clearly, if we do see something at this point, that would be a fantastic upside.

Anything what we do see in terms of responsiveness of the various endpoints compared to one another will help us select the appropriate primary outcome for our phase III study.

Out of reachable workspace, time function tests, and strengths, which of those will be included in the second half 2026 data release?

James.

James.

Yeah. I mean, we will have data on all of these endpoints. I think that we'll be able to give a summary of the above, but again, as I said, I wouldn't be expecting a priority to see significant changes in any of them.

Thank you.

Thank you. Our next question comes from David Hoang from Deutsche Bank. Please go ahead.

Hi there. Thanks for taking my questions. Maybe one on ELEVIDYS. Do you have any sense of how many centers are currently offering ELEVIDYS and maybe how does that compare to the number at the time of initial launch? Just quickly on Cohort A, could you talk about the regulatory path after you have the data in hand? Would this be like submitting an sNDA or just how should we think about the FDA interaction with Cohort A data? Thank you.

I don't think Have we given information on numbers of sites historically, Patrick?

I mean, we've talked about the number of sites that we've had just in the market. We've got, you know, 75 plus sites that are available and offering up ELEVIDYS, and that has not changed over time. It's still consistent out there.

We have also seen, again, in the green shoots category, we have seen sites that with some of the dislocation of last year, it paused, that have picked up and have commenced submitting start forms again. That's a positive green shoot as well. And with that, I'll turn the second part of the question over to Louise.

Sure. Once we have the cohort A data in hand, we'll meet with the agency, and then we'll determine the path forward after that. We've committed to share the data with them as soon as we have it, and that's we will meet with them and discuss.

You know, certainly we have to have a meeting with the FDA to figure out the exact regulatory process one has to go through. In the event this, the role of this data proves to be, change the risk benefit of this therapy significantly in favor of the non-ambulatory patient. We would hope that the agency would work with us to get this therapy offered to non-ambulatory patients as fast as possible for the obvious reason. Duchenne generally is a disease that doesn't permit waiting. It's just not a therapy that can wait. Every day these kids are damaged, no group of patients know that better than the non-ambulatory patients who have a desperate need for intervention to save what muscle that they have remaining after they've become non-ambulatory and have progressed the disease.

With that said, we're going to meet with the agency, as Louise has said, it is our very hope that the FDA will work creatively with us to get the indication back in the label so we can begin to have thoughtful conversations with physicians and families and offer this therapy to them.

Thank you. Our next question comes from Andy Chen from Wolfe Research. Please go ahead.

Hey, this is Brandon for Andy. Thanks for taking the question. You noted that ELEVIDYS or the business has stabilized. Does a return to growth assume only access in the ambulatory setting, or does that growth assume that you're able to resume treatment in non-ambo patients? Thank you.

Yeah, when we talk about return to growth, we're talking about in the ambulatory population right now. Obviously, with the success of sirolimus and cohort A, if it is successful, and we certainly have conviction that it will be, and getting that back in the label, then of course, we'll have to reforecast the post-op. When we talk about our initiatives right now and the return to growth, we're talking about the ambulatory population because obviously non-ambulatory is not in our label. We would never promote to non-ambulatory as it is not in our label. We're talking about ambulatory.

Thank you. Our next question comes from Jiayue Wang from Mizuho. Please go ahead.

Hello, this is Jiayue Wang on behalf of Warier. I guess I just want to ask about, you know, the 20% you mentioned the sites that are already using sirolimus. I guess what's holding the remaining 75% from adopting this regimen, assuming it's really gonna help reduce the ALI risk? Do you think it's because they're concerned about any immunosuppressing side effects, or they're just not familiar with the regimen?

Our best guess would be that education and information has to flow between physicians and thought leaders and the like. One of the things that we are not permitted to do is play a proactive role in that. We don't have sirolimus on our label. We can't promote to it. You know, the simple approach, which would be to go and share data with physicians, is something that we are not permitted to do. The spontaneous use of sirolimus in 25% of the physicians comes entirely from physician practice and from sharing of best practices among physicians.

I would anticipate it, that it would grow. We can't play a role in that growth. That will mute that growth until we get the cohort A data out. We get the ability to get this in the label for non-ambulatory patients in particular.

Thank you. Our next question comes from William Pickering from Bernstein. Please go ahead.

Hi. Thank you for taking my question. For DM1 and FSHD, are you seeing any difference in half-life across the two drugs and any implications that might have on dosing interval in a phase III trial? We read in the protocol documents that the FSHD half-life is expected to be twice as long as DM1, 5 weeks versus 2.5 weeks. Hence the question. Thank you.

Louise?

Sure. We're seeing similarities because we're using the same peptide across the programs. With respect to the timing interval, we are looking at 10 weeks versus 12 weeks in terms of the dosing interval. James, perhaps you'd like to comment on how we're analyzing that in the protocol.

Just to reiterate what you said really, Louise, that we're not expecting differential half-lives between the two products given that they are chemically very similar. Same ligand and just different siRNA cargo. The clinical data that we've seen is largely supportive of our preclinical data. We do think that we can probably drive a little bit better efficacy even than we've seen already by reducing dosing interval to 10 weeks. We will see those results as part of the cohort 5, DM1, and the subsequent FSHD, cohort 7.

Thank you. Our next question goes to Mitchell Kapoor from H.C. Wainwright. Please go ahead.

Hi. Thanks for taking our question. It's Jade on for Mitchell. Just on ELEVIDYS, could you comment on the recent FDA adverse event reporting system-listed fatality due to cardiac and breathing issues, which was reported three weeks ago? If so, how much time has elapsed between the patient receiving ELEVIDYS and this incident? How old was the patient? What was their ambulatory status? Do you have any information on the specifics of their DMD mutation?

Louise?

Yep. That was a commercially treated patient treated with ELEVIDYS, nearly 14 months post-treatment. Based on the available information, we analyzed it and it was deemed to be unrelated to ELEVIDYS treatment.

Thank you. Our next question comes from Brian Skorney from Baird. Please go ahead.

Hi, this is Luke on for Brian. Thanks for taking the question. Just wanted to get an update on your efforts of addressing AAV immunity, maybe to treat lower titer patients or eventual retreatment. Thanks.

Louise?

Sure. This data will be presented, so we have preliminary data from our apheresis study and some preliminary data from the study with Hans as well, indicating there is some ability to reduce titers in patients that have antibody positive. This is something that we've paused those studies for now, but something that we will certainly look to in the future, and that we do see the potential to lower antibodies and have an effect, but it would need more clinical study.

Thank you. This does conclude the question and answer session. I will now turn it back over to Douglas Ingram for closing remarks.

Yeah. Thank you for that. Thank you all for joining us this evening and for your very thoughtful questions. You know, we are, as I said before, tracking through 2026 with an enormous amount of opportunity in front of us. We have a very straightforward strategy to capitalize on that opportunity. We have four, in my view, tremendous therapies. Our goal is to maximize the opportunity with those four approved therapies, first and foremost for the Duchenne patients who benefit from them, but also for our investors. The second, of course, is our very strong financial position. You will have seen that we were profitable on a GAAP and a non-GAAP basis. We have over $750 million in cash and investments. We were cash flow positive.

If you exclude the Arrowhead payment, we'll be cash flow positive on a go-forward basis, even in our basest case with respect to our approved therapies. All of that allows us to fund this very exciting siRNA pipeline and to do it very independently. We've got a lot there. DM1, FSHD, Huntington's disease, IPF, SCA2, SCA1, SCA3, the research programs. We're really excited about them. We've seen some great data on DM1 and FSHD to lead the way, and we're very excited at the second half of this year to share with you more robust data still on both of those programs, which we think could potentially be best in class. The fourth pillar of our strategy is our employees.

We have a really dedicated group of very seasoned expert folks who, say what you will, have shown nothing but exceptional execution over these many years. I think taking those 4 pillars into account, we have one of the most exciting opportunities in front of us than we've had as an organization in our long history. I look forward over the course of the, this year to sharing more information on our execution and some of our milestones. With that, have a lovely evening, everybody.

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