Title

Presentation

Sarepta Therapeutics, Inc. beats earnings expectations. Reported EPS is $2.88, expectations were $0.976.

Operator: Good afternoon, and welcome to Sarepta Therapeutics, Inc.’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 Tamara Thornton, Sarepta Therapeutics, Inc.’s Director of Investor Relations. Please go ahead.

Tamara Thornton: Thank you, Antoine, and thank you all for joining today’s call. Earlier this afternoon, we released our financial results for 2026. The press release, along with our presentation slides and supplementary information, will be available on the Investors 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 Douglas Ingram, our CEO; 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 Therapeutics, Inc.’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 of Sarepta Therapeutics, Inc.’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 Therapeutics, Inc. 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 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, Douglas Ingram. Doug?

Douglas Ingram: Thank you, Tam. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics, Inc.’s 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 advance a pipeline with the potential to define Sarepta Therapeutics, Inc.’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 Alevitus, we believe that therapy is positioned to return to growth.

Second, Sarepta Therapeutics, Inc. 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, and 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, and our preclinical and research portfolio. And 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, and we look forward to additional readouts in the second half of this year.

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

To date, more than 1.3 thousand patients have been treated with Alevitus across clinical trials and commercial use around the world. The totality of the evidence continues to strengthen. The data show that Alevitus 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 one. We saw those benefits grow at year two. And yet again at year three, 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 Alevitus now before additional irreversible damage occurs. We have also seen supportive muscle MRI evidence showing that Alevitus dystrophin helps protect 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 and the urgency of intervening before further decline, more patients will move toward treatment.

That said, we are still in the middle of our commercial and educational efforts, and the path from consideration to infusion takes time. For that reason, we are reiterating our full-year guidance of $1.2 billion to $1.4 billion and would counsel prudence in raising estimates prematurely. Now, staying with Alevitus, we are also advancing our ENDEAVOR Cohort 8 study, which uses sirolimus as a pre-treatment. 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 enzymes 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 Alevitus 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 patient in our Huntington’s disease program, and we are progressing clinical trials in SCA2 and idiopathic pulmonary fibrosis. So, to summarize, the business is stabilized. Alevitus is supported by an increasingly compelling body of evidence. Our financial position is strong, and our high-value siRNA pipeline is advancing across multiple programs.

We believe Sarepta Therapeutics, Inc. is well positioned in 2026 and beyond. And with that, let me turn the call over to Louise, who will provide an update on our siRNA portfolio and broader development progress. Louise?

Louise Rodino-Klapac: Thanks, Doug, and 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, 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, these integrin receptors are highly expressed in muscle in addition to other tissues. They are also actively trafficked between the cell surface and the endosome through relatively well understood pathways. Nonclinical 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 is 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 1/2 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 1/2 study support the potentially differentiated attributes of SRP-1001, including a dose-dependent increase in plasma exposure up to the highest dose cohort, 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, and finally a favorable safety and tolerability profile with repeated dosing including no indication of anemia, which physicians have indicated represents 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 six months of follow-up for our 6 and 12 mg/kg MAD cohorts, which is equivalent to approximately 4 and 8 mg/kg of siRNA dosing. This will include safety, PK/PD data including circulating biomarkers and DUX4-related genes, as well as early functional data. We also plan to discuss our post–Phase 2 plans with FDA to define an optimal registrational pathway. Moving to DM1, SRP-1003 is an siRNA-based treatment designed to target and knock down DMPK mRNA in target cells. Study SRP-1003-101 is a first-in-human Phase 1/2 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, 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 directional and strong. As you are aware, DM1 is driven by an expanded CUG trinucleotide repeat in DMPK transcripts, causing mutant DMPK mRNA to accumulate in the nucleus and disrupt RNA splicing. As a result, for any therapy to be therapeutically effective, it must effectively target and knock down DMPK in the target cell. SRP-1003 is being developed to achieve exactly that.

We look forward to sharing results from additional SAD and MAD cohorts later in the year, which we expect will include multiple doses measuring mechanistic and functional endpoints with at least six months of follow-up for our 6 mg/kg cohort, which is equivalent to approximately 4 mg/kg siRNA. Specifically, we expect to share safety, serum and muscle PK, DMPK knockdown, CASI-20/2 splicing indices, and VHOT analyses. We will plan our IND submission for U.S. studies shortly after completing our MAD study. We believe these trials, if successful, will 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 are excited by the potential of our therapies to reach this standard.

In terms of our other siRNA pipeline programs, 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. Now turning to Alevitus, we were pleased to announce in March that screening and enrollment are underway for Cohort 8 of ENDEAVOR, 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 Alevitus in non-ambulatory individuals with Duchenne. Data from Cohort 8 will be used to determine whether administering sirolimus prior to and after Alevitus infusion helps reduce acute liver injury, a known risk associated with AAV gene therapy. The cohort is enrolling approximately 25 persons 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 Alevitus administration and will continue for 12 weeks after Alevitus administration. Primary endpoints include incidence of ALI and Alevitus 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 three-year functional data also reported at MDA, caregiver-reported impressions from EMBARK through two years of follow-up offer complementary perspectives on treatment impact beyond clinician-reported and performance-based outcomes. We are pleased that our body of evidence for Alevitus continues to grow with an unprecedented number of patients dosed as well as 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 4 observational study in 45 and 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 53 to traditional approval. 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. Sarepta Therapeutics, Inc. received feedback from the agency confirming that we were cleared 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 in April.

In summary, we have numerous value-building milestones upcoming across our Duchenne and siRNA portfolio. Thank you, and I will now turn the call over to Patrick for an update on our commercial performance. Patrick?

Patrick Moss: Thank you, Louise, and good afternoon. Today, I will summarize our performance for 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 Alevitus and $229 million for the PMOs. For Alevitus, 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 Alevitus 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 Alevitus’ benefit-risk profile. The treatment journey for Alevitus 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 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 and extending our reach within sites of care. In addition, 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 Therapeutics, Inc. sales team. Our sales team will devote time to more robust interaction 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 Therapeutics, Inc.’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 Alevitus requires time and trust.

To date, a growing body of empirical evidence supports that Alevitus is changing the trajectory of 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, and 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 Alevitus. HCPs and the ambulatory population were directly affected by misperceptions of Alevitus, so 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, but I do want to set expectations very clearly.

The time from enrollment form to infusion is a six-month process. Given this, it will take time to see the potential impact of my team’s actions 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—and the team is squarely focused on delivering the efficacy message to drive demand. For example, enrollment form activity is more geographically diverse. Sites that 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 Alevitus 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, and as Doug stated earlier, we reiterate the full-year guidance of $1.2 billion to $1.4 billion and would counsel prudence in raising estimates prematurely. Our long-term conviction in Alevitus remains strong. As the only FDA-approved gene therapy for Duchenne muscular dystrophy, we have treated more than 1.3 thousand patients in both the clinical and commercial settings.

The current and growing body of data demonstrates the disease-modifying potential of Alevitus, and as a result, we believe Alevitus has the opportunity to remain a cornerstone therapy in Duchenne for years to come. And 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 Therapeutics, Inc.’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 Alevitus, 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 will turn the call over to Ryan. Ryan?

Ryan Wong: Thank you, Patrick, and good afternoon, everyone. On behalf of the Sarepta Therapeutics, Inc. team, I am 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 will share highlights from the quarter and some perspective on how we are 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 Alevitus sales and was partially offset by an increase in collaboration and other revenue. 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 Alevitus 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 costs 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 investments, a sequential decrease of $206 million driven by $250 million of payments to Arrowhead—the second D1 milestone and the annual collaboration payment I just mentioned. Also, 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.

And 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 advancing both programs through late-stage 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. And with that, I will turn the call back to Doug. Doug?

Douglas Ingram: Thanks, Ryan. We will now open the call for questions.

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Operator: Thank you. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you will need to press 11 on your telephone and wait for your name to be announced. To withdraw your question, please press 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.

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

Douglas Ingram: I will turn this over to Patrick briefly to comment on some of the advisory boards you have had and some of the direct interactions you have had with physicians on the three-year data and other data.

Patrick Moss: Thanks, Doug. We have been having multiple advisory boards and discussions with physicians—both myself, Ian, and Doug one-on-one—and the field team as they are out there engaging. What is moving the needle is the efficacy data as well as the MRI data. Once physicians see both the divergence over time from natural history of patients treated with Alevitus, tied down with the MRI data, that is moving the needle and reflects exactly what they were expecting from a therapy like Alevitus as well as what they are seeing in their clinic.

Douglas Ingram: I think that is exactly right. There are a couple of reasons this is occurring. First, the data itself is really impressive. If you look at the one-year EMBARK data, on every secondary measure, every timed measure, we were statistically significant in this placebo-controlled and blinded study. Then you look at two years—on all measures, Alevitus is doing much better than untreated patients. That gap grows even more in year three, exactly what you would expect from a disease-modifying therapy that is changing the trajectory of disease. From an urgency perspective, we have muscle MRI data showing that if you get treated, you are going to save yourself from a lot of damage, the fat and fibrotic replacement that comes from that damage, and the loss of muscle.

It is understandable that it is compelling when you talk to physicians about all of this data, and that is not even all the data that we have; we obviously have the five-year data from our original cohort as well. The other important point is that, due to the events last year that distracted from what the therapy was doing for patients, there is a massive information gap in both the patient and physician communities around these issues. While that is frustrating, it is also a real opportunity. With the initiatives Patrick is putting in place, we have an enormous amount of confidence for the future. We more than doubled the size of our sales force. We have a contract sales force. We have brand data now. We have much better promotional material founded on that great data.

We have strong educational efforts in the patient community and the muscle MRI data that makes the point that you cannot wait—you will never catch up if you wait. There is enormous opportunity here to benefit patients and to get Alevitus moving. That said, as I noted earlier, these are long-cycle initiatives. We are reiterating our guidance of $1.2 billion to $1.4 billion and would ask you, along with us, to exercise prudence in changing estimates until these initiatives take fuller effect. The good news is that we are 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 exciting siRNA pipeline.

Operator: Our next question comes from Kostas Biliouris from Oppenheimer. Please go ahead.

Kostas Biliouris: Thank you so much for taking the question. One question on AMONDYS and VYONDYS sNDAs—and sorry if I missed it—can you clarify whether you have requested or received priority review there, and when should we expect the decision from the FDA? Thank you.

Douglas Ingram: These are sNDAs. We did not ask for priority review, so it is the regular time cycle. We would imagine that the PDUFA date will be sometime in February. Thanks.

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

Eliana Rachel Merle: Hey, guys. Just two questions from me. You mentioned some Q1 seasonal dynamics. Can you elaborate on what you saw there and how we should think about the appropriate run rate as we head into Q2 and beyond for both the PMO franchise and Alevitus? And then a question on the Huntington 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.

Douglas Ingram: Sure. I will turn the first part of the question over to Patrick, after which Louise can touch on the Huntington program.

Patrick Moss: Quarter-to-quarter dynamics are noisy, reflecting a small number of patients moving between this quarter or the next. It is not something we can be extremely precise on, but we do know things like illnesses and patient or family dynamics impact those quarterly dynamics, and that is something we evaluate as we provide guidance.

Douglas Ingram: One thing to remember is that Alevitus is a one-time therapy. With a chronic therapy, you build an installed base, and you are forecasting on the margin. With a one-time therapy, you are forecasting new every quarter, and with a therapy like Alevitus—net a couple of million dollars—a couple of patients catching the flu in the last week of the quarter can impact results. So, there is more variability here than you might see in a chronic therapy. And on the PMO side?

Patrick Moss: There is lumpiness in the ex-U.S. business as well. At the beginning of the year, we see insurance changes, and that does impact the PMO side of the ledger.

Louise Rodino-Klapac: Thank you. As you mentioned, we are very excited about the Huntington’s program, and we think that we are potentially differentiating for several reasons. First is the mechanism of action—using the TfR-targeting ligand in combination with subcutaneous injection. This allows us, based on preclinical data, to get into the deep brain regions essential for Huntington’s disease like the striatum. In mouse models and nonhuman primates, we have seen particularly high knockdown in these deep regions, which sets this program apart and got us excited. It is early days; we are on track for first patient-in. We will be looking for proof of biology in terms of safety and evidence of activity in terms of knockdown in the first data we see early next year. We are very much looking for differentiation based on the mechanism and the less invasive dosing relative to some other programs.

Operator: Our next question comes from Andrew Tsai from Jefferies. Please go ahead.

Andrew Tsai: Hey, congrats on the quarter. This is Matt Barkis on for Andrew Tsai. I just wanted to ask about what you are expecting in terms of ALI in the non-ambulatory Cohort 8 sirolimus 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, and might ALI rates in Cohort 8 actually mimic the real-world setting?

Douglas Ingram: I am going to turn this to Louise, but before I do, let me note that we do have some evidence before Cohort 8 that gives us confidence. Dr. Soslow, as you may know, has pretreated a number of patients and presented that data, I believe at World Muscle earlier this year. In that setting, pretreatment with sirolimus completely abated any increase in liver enzymes. Also, we have the real-world evidence study ENDEAVOR, and in an interim analysis there—early days, and overlapping with some of Dr. Soslow’s data—we have also seen no increases in liver enzymes so far when a patient is pretreated with sirolimus. Obviously, we need to dose more patients and get the Cohort 8 readout, but given that, along with our preclinical data and anecdotal experience from other physicians who have used sirolimus and other immunosuppression regimens, we feel significant conviction around the potential success of Cohort 8 and the ability to get back to offering this therapy to non-ambulatory patients who desperately need an option.

With that, I will turn it over to Louise to talk about the clinical trial itself and the standards pursuant to the statistical analysis plan.

Louise Rodino-Klapac: You are correct—we are looking for a 50% reduction in the incidence of ALI. The trial is an open-label study enrolling approximately 25 patients. We do have the ability to look at the data and enhance the N if required. Regarding the ability to reset by 50%, I will ask Dr. Richardson to comment on the clinical trial versus the real-world context.

James Richardson: Thank you, Louise. You are quite right that we have seen a different incidence of ALI in the clinical trial setting versus the real-world setting. That is partly driven by the use of the research assay GLDH in the clinical trial setting. We will be using that in Cohort 8, and so our primary analysis will be to look at a reduction of 50% or more versus our historical clinical trial rates, which include GLDH. We will also be able to look at it without GLDH to make sure that there is no specific signal to that biomarker. And as Louise said, as an open-label study, should we see anything that deviates from these original assumptions, we will be able to adjust the sample size accordingly.

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

Brian Corey Abrahams: Hi, guys. This is Kevin on for Brian. Thank you for taking our questions. Maybe following up on the 2026 Phase 4 ENHANCE study of patients receiving Alevitus 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 your considerations on potentially upsizing the current study versus running this real-world study in parallel as well. Thank you.

Douglas Ingram: Louise?

Louise Rodino-Klapac: I am going to turn this to Dr. Richardson in a minute, but at the highest level, the Phase 4 study gives us the ability to look at the use of sirolimus in ambulatory patients as well as looking at gene expression. These two elements are important for evaluating sirolimus in a population other than the non-ambulatory population. James, maybe you can give a few more details about the study.

James Richardson: Yes, absolutely. This is a study looking at commercially dosed patients under the same sirolimus regimen as we are using in Cohort 8. It is not part of a broader regulatory strategy, but simply tests the hypothesis about mitigation of ALI in a broader Duchenne population. The data could be supportive to Cohort 8, but it is not necessary for that non-ambulatory strategy. It will simply reaffirm the current hypothesis that sirolimus is equally well tolerated across a broad range of Duchenne patients, and we would expect similar efficacy in terms of reduction of ALI.

Douglas Ingram: Thank you.

Operator: Our next question comes from Analyst from Morgan Stanley. Please go ahead.

Analyst: It is Avi Novik on the line for Mike. Thank you for taking our questions. A quick one on guidance. I think on the prior call, you indicated that you were more comfortable with the low end of guidance, so that would be more likely. Given the positive green shoots you have seen early this year, would you be more comfortable that maybe the middle or high end of guidance might be more likely? If not, what do you need to see to get there? Thanks.

Douglas Ingram: Thanks for your question. You are exactly right—we guided $1.2 billion to $1.4 billion and advised folks to think toward the lower end until we see more. The short answer is that we are making very good progress in our initiatives, but they are long-cycle initiatives. A number have already gotten underway—for example, our salesforce is doubled and out in the field talking to physicians. We have great marketing material, with additional materials coming tied to our three-year data. We have educational efforts, and our contract salesforce has been trained and is getting into the field. That said, as excited as we are and given the conviction we have about these tools, we want to speak cautiously for the time being and be thoughtful.

We are not changing our guidance and would caution others to be prudent in raising internal estimates prematurely. Let us get these initiatives underway. We do see green shoots, and we see qualitatively that when this information is understood by physicians and patients, it has a meaningful impact. But it will take time, as these are all long-cycle efforts essentially resetting understanding of the evidence on both safety and efficacy.

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

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

Salveen Richter: Thanks for taking our questions. This is Tommy on for Salveen. Maybe if we could get details on patient numbers at dose levels for the siRNA data by year end, and especially how the functional measures for this data factor into how you are thinking about the registrational outlook and competitive comparisons. Thank you.

Douglas Ingram: I will turn this to Louise.

Louise Rodino-Klapac: Sure. For FSHD, we will have data from our 6 and 12 mg/kg MAD cohorts—our highest dose cohorts—which is equivalent to approximately 4 and 8 mg/kg siRNA. For DM1, we will have follow-up from our 6 mg/kg MAD cohort, equivalent to approximately 4 mg/kg siRNA. As mentioned, we will be looking at safety, biomarkers, and early evidence of functional outcomes. Dr. Richardson can comment on how we are thinking about the functional data, noting it is early in terms of follow-up and patient numbers.

James Richardson: Primarily, safety and PD biomarkers will help us select the appropriate dose to carry forward into the Phase 3 program. We will also look at the functional data to understand the most responsive outcomes that help us select and drive our Phase 3 design. I would not expect significant movement in functional measures at six months in FSHD. In DM1, we would expect to see a signal in VHOT at this timeframe, but for other timed function tests, it is very early in this disease state and cohort size to make definitive conclusions.

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

Tazeen Ahmad: 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 have presented so far to products that have already shown data that might be further ahead in development? Specifically, how should we be thinking about what the right endpoints should be in order to look at? I know there is a Novartis study that is being debated as to whether or not in DM1 the right endpoint is being used. I would love to hear your thoughts on that. And secondly, as you talked to FDA about the shift to get the PMOs to traditional approval, can you talk about if there has 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.

Douglas Ingram: Thanks. I will turn this over to Louise.

Louise Rodino-Klapac: Regarding comparative data, as we mentioned, what differentiates our program is the amount of siRNA we are getting into muscle using the alpha v beta 6 targeting ligand. The more you can get into muscle, the more knockdown you can get, which leads to better biomarkers and downstream functional markers. With early data, our focus is achieving the highest level in muscle to have the most robust effect and give us the best chance of efficacy and consequent function. With regards to functional outcomes in DM1, Dr. Richardson can comment. On the PMOs, we are generally interacting with the same individuals at the agency that we have been for the PMO programs and for those sNDAs.

James Richardson: In DM1, we are seeing the usual evolution in understanding of functional endpoints as developers move into the space, alongside greater investment in natural history data. For example, Nick Johnson’s group has published from the NDM1 study, building our understanding of appropriate functional outcomes. From our point of view as a sponsor, without commenting on other sponsors’ programs, we can take these natural history data internally, speak to experts like Nick Johnson and others, and combine their views with functional data from our Phase 1/2 cohorts to reach our own view on the most appropriate primary and secondary endpoints for Phase 3, and then discuss that with the FDA.

Operator: Thank you. Our next question comes from Joseph Schwartz from Leerink Partners. Please go ahead.

Joseph Schwartz: Thanks very much. I have a question on the siRNA programs, which will have data 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 profiles? And then in DM1, what specific magnitude of splicing correction would you want to see in the upcoming MAD cohorts to prove that 1003’s differentiated delivery can translate into a best-in-class clinical profile? And why would VHOT not improve fairly quickly for your approach since it has seemed to be fairly sensitive for other RNA approaches early on?

Douglas Ingram: I will turn this to Louise. I will note that I think Dr. Richardson suggested that VHOT may be an appropriate measure to see a signal in the MAD, but longer-term functional endpoints require more time.

Louise Rodino-Klapac: On FSHD and knockdown of DUX4: DUX4 should not be expressed in adult muscle—it is expressed early in development and then turned off. Any stochastic expression in adults is toxic, so deeper suppression is beneficial. For DM1, we are looking for increases in muscle concentration leading to improved DMPK knockdown. From preclinical data, DMPK knockdown correlates with functional improvement. Based on the data to date, we have seen dose-dependent increases in muscle exposure. We will be looking at DMPK knockdown with our MAD data later in the year. On VHOT, we would expect earlier signals, as VHOT is an early sign of function.

James Richardson: I completely agree—just to distinguish between VHOT, where we do think we will see a signal at this point, and other functional outcomes, which will take longer.

Operator: As a reminder, to ask a question, please press 11 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.

Analyst: I am just curious if you could comment on the mechanistic rationale for the greater-than-linear increase in exposure observed at lower doses in FSHD, 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 Rodino-Klapac: We certainly saw an increase that was not linear at the lowest dose, which was not unexpected based on preclinical data. We would expect exposure to start to plateau at higher doses based on preclinical data, while still continuing to increase, though less than proportionally, at the higher dose levels.

Analyst: And then just one follow-up. With regard to the study that you mentioned for sirolimus in the real world where you did not see any evidence of liver enzyme elevation, could you just expand on that in the sense that were there any cases observed?

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