SRPT - NASDAQ

Good day and welcome to the Sarepta Therapeutics Third Quarter 2024 Financial Results Conference Call. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] As a reminder, today's conference is being recorded. At this time, I would now like to turn the call over Mary Jenkins, Associate Director, Investor Relations and Corporate Communications. Please go ahead.

Thank you, Michelle, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the third quarter 2024. The press release is available on our website at sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram; Ian Estepan; Dallan Murray; and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that, during this call, we will be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations, and trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual quarterly report on Form 10-Q filed with the SEC, as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statement, including any financial projections provided today based on subsequent events or circumstances. And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Thank you, Mary. Good afternoon and thank you for joining Sarepta Therapeutics third quarter 2024 financial results conference call. I am pleased to report another strong quarter of commercial performance. Earlier today, we reported total net product revenue of about $430 million growing at 39% versus the same quarter last year. ELEVIDYS net product revenue was $181 million. Our ex-US partner Roche has made good progress in the quarter and if one includes the royalty revenue from Roche's ex-US ELEVIDYS performance, we achieved $190.5 million in the quarter. Even without considering royalty revenue, our ELEVIDYS performance substantially exceeded our prior guidance as well as analyst consensus. We are tracking well to Q4 and 2025 performance consistent with prior guidance. Our PMO sales comprising EXONDYS 51, VYONDYS 53 and AMONDYS 45 achieved approximately $249 million in the third quarter, again substantially exceeding analyst consensus. As anticipated, we are not yet seeing material cannibalization of our PMO franchise from ELEVIDYS performance and we do not expect to see meaningful net cannibalization through 2025. I am also pleased to report that we were again profitable on a GAAP and non-GAAP basis in the third quarter. Dallan Murray, our Chief Customer Officer, will provide more color on commercial performance in a moment. Turning to R&D, we have rationalized and prioritized our pipeline this quarter and we've made great progress advancing programs. Before I discuss our progress, let me discuss our PPMO program. You will have seen in our release that we have made the decision to discontinue the SRP-5051 development program. This was done after dialogue with the FDA and their requirements after our own risk benefit analysis for the program and in consideration for the evolving landscape for Duchenne, including the approval of ELEVIDYS. Now one never takes lightly the decision to discontinue a program, but we are confident that our decision is the right one for the patient community and for our stakeholders. Moving to our pipeline progress, we are beginning to move rapidly into late stage clinical with a planned approval BLA in 2025 for SRP-9003 to treat limb-girdle muscular dystrophy or LGMD type 2E, the commencement of our trial for SRP-9004 to treat LGMD type 2D in the fourth quarter of this year and the commencement of our trial for SRP-9005 to treat LGMD type 2C in early 2025, both of which trials are intended to support accelerated approval. We have also made progress with our clinical development efforts for ELEVIDYS, including clinical activity to support ex-US approvals and meet our post marketing commitments, data presentations that speak to the value of ELEVIDYS to those living with Duchenne and clinical development work intended to expand the population for ELEVIDYS. Additionally, our program to move ELEVIDYS to suspension manufacturing is proceeding very well. We have had very encouraging interactions with the FDA, and we continue our engineering runs in anticipation of commencing a bridging study in 2025. We have also made good progress with the rest of our neuromuscular CNS and cardiomyopathy pipeline and intend to share more concerning our pipeline and its progress in 2025. Our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac will discuss this decision and our R&D progress in a moment. And with that I will turn the call to Dallin Murray for more detail on commercial performance and our plans. Dallin?

Thank you, Doug, and good afternoon. We're pleased to report an impressive third quarter led by the continued strength of the ELEVIDYS launch. The success and performance we've achieved since approval has been and continues to be driven by robust patient demand from both the ambulant and non-ambulant populations, ample site capacity, positive trends in access and reimbursement, and consistent conversion rates, as we continue to see patients gaining access within the three to five-month conversion timeline. Additionally, as the team works to execute on the broad label, it's important to note that we've thoughtfully built a model which allows us to flex as needed to accommodate demand from different segments, such as the older non-ambulatory patient population. Turning to the third quarter revenue numbers. Net product revenue for ELEVIDYS reached $181 million and grew by nearly 50% compared to the prior quarter, exceeding our guidance of quarter-to-quarter growth of 30%. Of note and looking forward, I remain impressed with our team's ability to forecast. As we have shown with our performance this quarter, we have good visibility on the launch dynamics and as predicted, we are now at the inflection point on the launch curve. Further enhanced by the wealth of data presented at World Muscle that Louise will discuss. We have strong momentum going into the fourth quarter and reiterate our previously stated Q4 guidance, which is in line with the current Q4 consensus. Based on all of these factors and our confidence in meeting the Q4 expectations, we remain in a strong position to achieve guidance for 2025. The progress made by this team is unprecedented in our industry. We've anticipated all of the factors necessary to execute on a broad label and our performance provides clear evidence of our continued ability to meet expectations and execute as promised. So, to summarize, we continue to see high demand, strong conversion rates, and we are impressed with how sites of care are successfully treating patients at an unprecedented rate. Together, we are changing the face of Duchenne muscular dystrophy in the United States. Turning to our PMO franchise, which also achieved impressive results in the third quarter. Importantly, we expect to see continued strength in the coming quarters and years. We delivered roughly $249 million in net product revenue and with approximately 4% growth in Q3 compared to the third quarter of 2023, the PMOs represent a healthy and solid segment of our Duchenne franchise. EXONDYS 51 led the way for the PMOs with $140.7 million in net product revenue. VYONDYS 53 delivered $32.2 million in net product revenue in the third quarter, and we delivered $75.9 million in net product revenue for AMONDYS 45 in Q3, representing growth of nearly 15% compared to Q3 of 2023. In closing, I'd like to thank the Sarepta team and all of our partners, whether at the sites of care or elsewhere. And most importantly, I'd like to thank the patient community who have been with us on this pioneering journey, every step of the way. We're grateful to be exactly where we had always wanted to be and that is with approved therapies serving the vast majority of the Duchenne patient community. And with that, I'll hand the call over to Dr. Louise Rodino-Klapac for the R&D update. Louise?

Thanks, Dallin. I'll begin my remarks with ELEVIDYS and then provide an update on our pipeline. We continue to advance the ELEVIDYS clinical program and share new datasets as they become available. We recently published the primary one year EMBARK results in Nature Medicine, a high impact journal. In addition, we had multiple presentations at the World Muscle Society Congress in early October. This included additional EMBARK data, Muscle MRI and Cardiac MRI. Muscle MRI changes were consistent with functional outcomes from EMBARK Part 1, showing stabilization or slowing of disease progression with SRP-9001, while progression occurred in placebo treated patients evidenced by accumulation of fat and fibrosis. Cardiac MRI demonstrated that at one year post gene therapy there was no evidence of harm observed. Future longitudinal cardiac MRI studies will assess long-term protection of cardiac muscle. As we previously described, ELEVIDYS contains an MHCK7 promoter that expresses well in the heart to protect cardiac muscle. We have shown in the mdx rat model of Duchenne improvements in cardiac function as well as overall survival. In addition to the EMBARK data, we've also presented safety and expression data from Study 103 or ENDEAVOR, demonstrating consistent safety and expression data across ambulatory and non-ambulatory patients. As of the end of October 2024, we have dosed over 80 late ambulatory and non-ambulatory patients within our clinical program and continue to see a consistent safety profile. Finally, we shared five-year longitudinal data from Study 101 demonstrating that SRP-9001 stabilizes or slows DMD progression with an increase in divergence from natural history over time. As shown by external control analysis and supported by the independent cTAP analysis. No new safety signals were identified. As mentioned on our last call, the ELEVIDYS accelerated approval for non-ambulatory patients includes a post marketing commitment to confirm clinical benefit which will be addressed via our non-ambulatory and late ambulatory Study 303 also known as ENVISION. As a reminder, ENVISION is a global randomized double-blind placebo controlled two-part study. ENVISION is progressing well with US enrollment complete and the remaining recruitment occurring ex-US. Enrollment is expected to be completed in 2025 with our last patient last visit expected in 2027 following an 18-month placebo-controlled period. We also continue to advance clinical studies that monitor long-term follow up with the ELEVIDYS. Our long-term follow up studies include ENDURE and EXPEDITION. As a reminder, ENDURE is a Phase 4 observational study that will follow individuals treated with ELEVIDYS for up to 10 years. In addition, EXPEDITION is a Phase 3 study enrolling approximately 400 patients that were previously enrolled ELEVIDYS clinical trials and followed for consistent safety and efficacy measures for up to five years. Regarding patients currently ineligible to receive ELEVIDYS under the expanded label, we continue to advance multiple studies. For the approximately 15% of patients who are screened out for preexisting anti AAV rh74 antibodies, we have commenced two studies, one with embodies to cleave antibodies and a second with plasmapheresis to remove antibodies. We expect to have expression and safety data from fentanyl patients in early 2025. In addition, for patients under the age of 4, we've treated patients as young as 2 in our Study 103 and together with our partner Roche, we are executing Study 302 involved to gain experience dosing patients under 4 and as young as 3 months. We continue to communicate the range of trial experience in patients treated with ELEVIDYS from those that are under 4 to those with more advanced disease. Moving now to our programs for the limb-girdle muscular dystrophy or LGMD. Starting with SRP-9003. As we mentioned on the first quarter call, we initiated dosing early this year and study SRP-9003-301 also known as EMERGING [ph] or Phase 3 multinational open label clinical trial of SRP-9003 for the treatment of limb-girdle muscular dystrophy type 2E for beta sarcoglycanopathy. The agreed primary endpoint of EMERGING is expression of beta sarcoglycan, the absence of which is the sole cause of the disease. The study is on track to be fully enrolled by the end of 2024. Assuming a positive pre BLA meeting, we will anticipate a BLA filing in 2025. We are encouraged by the agency's willingness to support a viable pathway for SRP-9003, an ultra rare genetic condition that is progressively debilitating, results in loss of ambulation and leads to early mortality. The ability to progress a small NF15 biomarker study, together with our ability to demonstrate delivery of a functional beta sarcoglycan protein is extremely important not just for this program, but for the other sarcoglyconopathies in our pipeline, including LGMD2D and LGMD2C, both of which are progressing to the clinic. Having successfully advanced SRP-9003, we submitted our SRP-9004 IND update reflecting our suspension process this year with Phase 1 initiation expected by year's end. As a reminder, SRP-9004 is designed for the treatment of limb-girdle muscular dystrophy type 2D or alpha sarcoglycanopathy. Finally, we are also rapidly progressing our program for SRP-9005 for the treatment of limb-girdle muscular dystrophy type 2C or gamma sarcoglycanopathy. We plan to engage with FDA in Q4 of this year with plans to initiate a clinical study in Q1 2025. To summarize, we are very pleased with the progress of our LGMD portfolio and expect to have three of our LGMDs in the clinic in less than six months. We are maximizing the synergies across this platform from both an R&D and manufacturing perspective, and our sites are firmly set on accelerating the remainder of the LGMD assets to the clinic. Continuing with our RNA platform and beginning with our PMOs, the ESSENCE trial, our post marketing requirements for golodirsen and casimersen as well as mission or post marketing commitment for EXONDYS are both fully enrolled and remain on track. We look forward to sharing data as soon as the study is complete. Turning now to PPMO. As announced today and in line with our unwavering commitment to patients first, we have decided to discontinue development of SRP-5051, also known as vesleteplirsen, our investigational peptide-conjugated PMO or PPMO to treat Duchenne. This means dosing and our momentum study SRP-5051-201 has stopped. The safety of study participants is our highest priority, and while we are encouraged by the dystrophin expression results with SRP-5051, the long-term safety in a chronic treatment setting does not support further development. Our initial hypothesis was that the hypomagnesemia was manageable and monitorable. Although events thus far remained medically manageable in a small number of patients, we saw persistent hypomagnesemia despite treatment discontinuation, and our risk benefit analysis led us to end the study. The MOMENTUM study has provided important information around the use of RNA targeted therapies to increase dystrophin production in Duchenne, and we are extremely grateful to the patients, families and clinicians who participated in our studies. Now, let's spend a moment discussing our current and future pipeline. During the past six years since I joined Sarepta, we've been diligently building expertise and capabilities to advance our current portfolio and identify new assets. We've significantly advanced the field of genetic medicine through clinical trials and advanced research for patients with preexisting antibodies and the potential for redosing. We've also advanced regulatory precedent for gene therapy for rare disease as evidenced by a rapidly developing LGMD platform. On the research side, we have optimized, developed and characterized new AAV capsids that will change the landscape for neuromuscular gene therapy and unlock potential in cardiac and central nervous system disease areas. As an example, we've optimized the construct for Charcot-Marie-Tooth type 1A or CMT1A using AAV rh74 and are now rapidly advancing to the clinic following exciting preclinical data. As a reminder, we are using a surrogate approach for delivery of the neurotrophin-3 or NT3 gene to improve myelination and nerve regeneration in CMT1A. This pipeline in a product approach has applicability to other CMTs as well as other demyelinating indications. We look forward to highlighting our impressive pipeline in an R&D Day in 2025. I'll close by thanking all the patients who participate in our trials and my incredibly talented R&D colleagues who make all of this possible. The future is bright because of their work. I'll now turn the call over to Ian Estepan for an update on our financial results. Ian?

Thanks Louise and good afternoon, everyone. The financial results press release provided details for the third quarter of 2024 on a GAAP basis as well as a non-GAAP basis. Please refer to our press release available on our website for full reconciliation of GAAP to non-GAAP financial results. As a reminder, beginning in the fourth quarter of 2023, amortization of in license rights and income tax expense are no longer excluded from non-GAAP results. The company has added the income tax effective adjustments which represents the estimated income tax impact of each of our pretax non-GAAP adjustments based on the applicable effective income tax rate. Non-GAAP financial results for the third quarter of 2023 have been updated to reflect this change for comparability purposes. So for the three months ended September 30, 2024, the company recorded total revenues of $467.2 million which consists of net product revenues in collaboration and other revenues compared to revenues of $331.8 million for the same period 2023, an increase of $135.4 million. Net product revenue for the third quarter of 2024 from ELEVIDYS was $181 million compared to $69 million same period of 2023. Net product revenue for the third quarter of 2024 from our PMO EXONDYS skipping franchise was $248.8 million compared to $240 million for the same period of 2023. The increase in net product revenue primarily reflects the net product revenue associated with sales of ELEVIDYS. For the three months ended September 30, 2024, the company recognized $37.4 million of collaboration and other revenues which primarily relates to the commercial ELEVIDYS supply delivered to Roche and royalty revenue from Roche compared to collaboration revenues of $22.5 million for the same period of 2023, an increase of $14.9 million. The reimbursable codevelopment cost under the Roche agreement totaled $61.5 million for the third quarter of 2024 compared to $34.9 million for the same period of 2023. As a reminder, these Roche reimbursable codevelopment costs aren't offset to our operating expenses. On a GAAP basis, we reported a net income of $33.6 million or $0.35 per basic share and $0.34 per diluted share and a net loss of $40.9 million or $0.46 per basic and diluted share for the third quarters of 2024 and 2023, respectively. We reported a non-GAAP net income of $67 million or $0.62 per diluted share in the third quarter of 2024 compared to a non-GAAP net income of $31.5 million or $0.31 per diluted share in the third quarter of 2023. In third quarter of 2024 we recorded approximately $91.7 million in cost of sales compared to $37 million in the same period of 2023. The increase in cost of sales primarily reflects the cost of sales related to ELEVIDYS during the three months ended September 30, 2024, following the label expansion in June. On a GAAP basis, we recorded $224.5 million and $194.3 million in R&D expenses for the third quarter of 2024 and 2023, respectively, a year-over-year increase of $30.2 million. The increase primarily reflects a $55.4 million cost associated with the termination of an inherent commercial manufacturing and supply agreement net of the reimbursement termination cost by Roche, partially offset by a decrease in clinical and manufacturing activity for our PPMO and Eteplirsen program. On a non-GAAP basis, R&D expenses were $199.8 million for the third quarter of 2024 compared to $163.9 million for the same period of 2023, an increase of $35.9 million. Now turning to SG&A. On a GAAP basis, we recorded approximately $128.2 million and $120.9 million of expenses for the third quarters of 2024 and 2023, respectively, an increase of $7.3 million. The increase was primarily driven by an increase in professional services used to support the continued efforts to commercialize the ELEVIDYS and an increase in compensation and other personnel expenses primarily related to the changes in headcount. On a non-GAAP basis, the SG&A expenses were $100.2 million for the third quarter of 2024 compared to $92.8 million for the same period of 2023, an increase of $7.4 million. On a GAAP basis, we recorded $11.8 million in other income net for the third quarter of 2024 compared by $12.3 million of other loss net for the same period of 2023. The change is primarily due to an impairment of a strategic investment during the three months ended September 30, 2023 with no similar activity in 2024. We had approximately $1.4 billion in cash, cash equivalents, investments and long-term restricted cash as of September 30, 2024. So, to conclude, unsurprisingly our strong commercial execution and our continued focus on expense management has put us in a strong financial position. We now expect to be sustainably profitable from both the GAAP and non-GAAP perspective and will turn cash flow positive early in 2025. And with that I'll turn the call back over for Doug to start the Q&A. Doug?

Thank you very much, Ian. And Michelle, let's open the call for questions.

Thank you. [Operator Instructions] Our first question is going to come from the line of Tazeen Ahmad with BofA Securities. Your line is open. Please go ahead.

Hi, good evening, guys. Thanks for taking my question. I wanted to clarify what you said a little bit earlier when your prep remarks about maintaining guidance for the rest of the year. So, when you gave us original guidance, you had said that based on the number you expected in 3Q that you would guide to 100% upside for 4Q results. Now that you've beaten expectations, can you tell us what that base number is? Is it 100% upside from what you just reported? Thanks.

Yeah. We feel very comfortable with the guidance we gave before which was we'd be 100% above the guidance that we had for Q3. I will also linger and note that we are continuing. We continue to be very, very comfortable with the guidance we gave for 2025, the long-term guidance, $3 billion, about two-thirds of which will be ELEVIDYS and one-third of which would be our PMOs. And we're also very confident in our long-term projections which would have peak year sales across the four approved therapies at $5 billion or more and that we would be treating with the ELEVIDYS, the prevalent population over the course of the 2020s into -- around 2030 or so and we'll be growing for some number of years.

Thank you. And one moment for our next question. Our next question comes from the line of Gena Wang with Barclays. Your line is open. Please go ahead.

Thank you. Since I can only ask one question, I will ask about the PPMO discontinuation 5051. So maybe can you give a little bit more color regarding the hypo magnesium? Is that the main concern FDA raised? And can you give a little bit more color since at what point that you see more severe cases? And also, when we -- the old data back at the 30 milligram at the 12 weeks was 6.55% protein expression. And at that time, you project it could be over 10% at 96 weeks with the protein level is still in line with what you projected and is mainly is the safety. And are you planning to complete discontinue the PPMO franchise?

Yeah. So, I will -- first of all, thank you for your question, Gena. I'll turn the question over to Louise to make some comments about our decisions regarding the PPMO program.

Certainly, I'll try to make sure I remember all of the parts. So, on the franchise, we are discontinuing the entire PPMO franchise. They all use the same cell-penetrating peptide. And so this also includes the discontinuation of the other PPMO programs. The decision to stop the program was based on -- through multifactorial. So, it included our discussions with the FDA, which we've had on the development of that. At this point, the FDA said that the accelerated approval pathway was not open based on the current profile. To date, it was primarily based on our own benefit risk assessment. And that was including safety, which included the hypomagnecemia that we saw, which consisted of prolonged hypo magnesium, magnesium in some cases. And then the evolving landscape of Duchenne, including the approval of ELEVIDYS. So, taking all of those things together led to our decision.

Let me just contextualize all this just to remind folks, so commencing really In February of 2018, the FDA had confirmed that it had a precedent for the use of the accelerated approval pathway for PMOs. And that precedent was really rested on two things. It's obviously rested on the value of dystrophin production for Duchenne muscular dystrophy. But it also rests as well on the safety of the morpholino oligomer nucleotides, the PMOs. And that safety profile itself is very laudable. It's second really to almost none. When one attaches a delivery MODI [ph] to a PMO, then you will change that safety profile potentially in that risk benefit analysis. And I think the agency wasn't comfortable with the concept of accelerated approval in light of this change. And then, of course, we independently did a risk benefit analysis and concluded that the program shouldn't continue. So that's where we are. And I think this is in the first and foremost, first and foremost, it is in the benefit of the patients that we serve. And then secondly, of course, it benefits our other stakeholders as well.

Thank you. And one moment for our next question. And our next question is going to come from the line of Andrew Tsai with Jefferies. Your line is open. Please go ahead.

Hey, thanks. Good afternoon. Congrats on the execution. Thanks for taking my question. So, about the ELEVIDYS launch, your partner Roche made a comment about two weeks ago how 500 patients have been treated worldwide so far, including 450 in the US. so can you help us reconcile that 450 US patient number, presumably a good chunk are in clinical trials, but even backing out those patients, we could be getting a nice implied jump in Q4 sales that could be above your Q4 guidance. So maybe help us reconcile that. Thank you.

Yeah. Andrew, I'm not going to comment or confirm that we haven't provided those numbers like that. We're going to use revenue as our metric and we're, as it stands today, standing on the guidance that we've provided previously. I mean, it certainly is the case qualitatively that we have dosed an enormous number of patients. We have an extraordinary amount of experience with ELEVIDYS. Louise will have mentioned to you that we have already dosed between clinicals and some commercial 80 or so, probably more than that by now. About 80 patients that are either late ambulatory or non-ambulatory, in addition to all of the other patients we dose. And as you know, we've not seen a difference in any safety metrics. So things that look great. The profile of the therapy looks great and the launch is going great. So that's where we are right now with it. And we're excited to give you an update after Q4.

Thank you. And one moment for our next question. Our next question is going to come from the line of Brian Abrahams with RBC Capital Markets. Your line is open. Please go ahead.

Hi, this is Kevin on for Brian. Thanks for taking our questions. I just wanted to ask, can you speak to what progress you've made in conversations with payers on broader coverage policies and maybe can you speak more to your efforts in insuring Medicaid coverage policies, and if you can remind us what proportion of patients with DMDU [ph] estimate to be on Medicaid. Thanks a lot.

Yeah. So it's about -- Dallan, following my remarks, if there's anything to add or if I've made a fundamental error, you can correct me. Broadly speaking, it's about 50% commercial. 50% Medicaid. Things are going very well. Interactions both from a Medicaid perspective and a commercial perspective are very productive. And one of the things that we're really benefiting right now is a couple things. One, the amount of evidence and data that we have that supports bringing ELEVIDYS to a broad group of Duchenne patients is great and gives us a lot to talk about. The depth of the conversations that we're having with payers and the quality of those conversations is absolutely fantastic. And we're all benefiting from this. If one focuses down on Sarepta itself, we have become very expert over the last nearly a decade, about eight years, in working with payers and gaining access to patients for our therapy. At the same time, in fairness, physicians have become increasingly more sophisticated in how to manage through the process to get kids on therapy. And payers, both Medicaid and commercial, have become far more experienced with Duchenne muscular dystrophy and how that disease works and the like. So that the entire quality of the discussions are far more productive than they may have been some eight years ago. And it's also resulting in the performance that you're seeing today, which is, of course, very, very good launch, which is matching the trajectory that we had imagined that we would have with all of the work that we did to prepare ourselves for this launch.

Thank you. And one moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open. Please go ahead.

Thanks for taking our question. This is Tommy on for Salveen. So just on the 2Q call, I believe it was mentioned that there were some infusions that were rescheduled from 2Q to 3Q. Is it possible to quantify that impact? And more broadly, what's the latest thinking on how to think of the tail end of the launch and the peak year? Thanks so much.

The first part of the question I will turn over to Dallan. The second part of the question is that what I will say to you right now is that we're going to go through a period of significant growth over the course of this decade, and we will get through the prevalent population by 2030. With that said, Dallan, if you want to comment a little more on Q3.

Yeah. If the question was if that impacted our performance or our guidance in any way, remember we guided off of Q2 sales growth off of Q2 sales. So that was factored into our guidance and expectations for Q3 and Q4 already. So, there's no real quantification of the impact of that.

Thank you. One moment for our next question. Our next question comes from the line of Anupam Rama with JPMorgan. Your line is open. Please go ahead.

Hey, guys. Thanks so much for taking the question. Just a quick one for me. You've given a little bit more details on kind of your internal pipeline focus here in the near term. Looks like we're going to hear a little bit more at an R&D Day in 2025. Just wondering how we should think about sort of the time and resources spent on the internal pipeline versus you guys doing some external business development. And I know you guys only said one question, but since it's third quarter earnings, if I could just ask if you might bring me an ounce at a small healthcare conference in January, that would be cool. Thanks.

Okay. So, first of all, let me -- first of all, thank you very much for your question, Anupam. As relates to your first question, let me say that, we have -- we are really focusing right now on two major and very important things. One, of course, is the launch of ELEVIDYS, which as you can see right now hopefully is going swimmingly. And that's not -- that's the result of an enormous amount of work over many years by a lot of folks. And also in that first part is the continuing performance of the PMOs, which themselves are doing very well, bringing a better life to kids, very durable and so far not seeing any significant impact from the launch of ELEVIDYS. So all fantastic there. The second big effort of this organization right now is advancing our internal pipeline. We're getting a lot of great traction there. There is a lot of excitement. We're going to do kind of a curtain raise next year and really show you some of the deeper pipeline and some of the things that we're very excited about. But even in the near term, in the late stage, you can see we are in the next few months really we'll be in clinical trials on three of our limb-girdle programs. So that's really beginning to accelerate and we're very, very excited about that. That's what we're focused on as an organization right now. Yes, we are going to go as Ian, as I said, we're going to be profitable from a GAAP and a non-GAAP basis on a go forward basis as we have been in prior quarters now. And we're going to be cash flow positive really starting very early next year and that gives us some opportunities to think even more broadly. But if you're asking us about the things that we're focusing on right this minute, right now, it's ensuring the success of our four approved therapies, including the launch of ELEVIDYS and really advancing and accelerating our internal pipeline which we are excited about. Now on the second one, I'm not going to make any commitments as we stand here right now. We have had, as you know, a history of doing some pre-announcements at that conference in January. But, of course, we'll wait and see in January what we do there. But we will likely be consistent with history. That's where we are.

Thank you. One moment for our next question. Our next question is going to come from the line of Danielle Brill with Raymond James. Your line is open. Please go ahead.

Hi, guys. Thanks so much for the question. So, by our math, there was about 20 additional patients treated in 3Q versus 2Q. And for all intents and purposes it sounds like the launch is going great. So, I guess, we just thought that the step up in treatment rates could be more pronounced following the label expansion. Can you just talk a little bit more about what you're seeing in the market and what the main bottlenecks are to giving these kids treated? Thanks.

Let me just say again -- first of all, we're going to -- when we talk about performance, we're going to talk in revenue as our market. We're not going to use other metrics and we're very, very excited about the progress of our launch. And it's going exactly to plan and we're seeing the trajectory that we had envisioned and we spoke about a few quarters back. So, everything is going fantastic. The shape of that growth is a combination broadly of three things and it always will be. Some of it is -- piece of it is site capacity. And that's not simply a matter of getting more sites up and running. It's making sure that you have sites that are well educated, well informed, expert and that they have the ability to manage and monitor kids post dosing so that we always have this extraordinarily positive safety and efficacy profile that we have today with ELEVIDYS, at least from my perspective. The second one, of course, is just manufacturing and batch release and making sure that we are thoughtful about that. The third one is payer interactions which are going great both from a Medicaid perspective and a commercial perspective. Everything is going very well. So things are tracking exactly as we had hoped. And that's why we're able to reiterate the guidance that we provided previously both about Q4 and our guidance for 2025, which is $3 billion is the mean of that and our long-term forecast and the fact that we will be going through a period of multiple years of significant growth as we over the course of this decade treat the prevalent population even as we are also treating the incident population now and deeply into the future.

Thank you. And one moment for our next question. Our next question comes from the line of Eliana Merle with UBS. Your line is open. Please go ahead.

Hey, guys. Thanks for taking the question. Can you just elaborate a bit more on your comments on site capacity just now? Just the latest that you're seeing. You mentioned you're seeing ample site capacity, but I guess how many sites dose patients in 3Q and I guess how dispersed or concentrated has this dosing been across the sites? Thanks.

Yeah. So we have about -- so I'll just say broadly, we have about 75 sites. They might modestly increase over time reactively. And Dallan can provide an answer to us on, as we sit here today, what percentage of those sites have actually been dosing sites?

Yeah. The vast majority of centers have dose patients and we really don't get into specifics quarter to quarter on how concentrated these sites are. So, as Doug had said earlier, we're guiding our -- we're focusing our guidance on revenue, net product revenue.

Thank you. And one moment for our next question. Our next question is going to come from the line of Gil Blum with Needham & Company. Your line is open. Please go ahead.

Hey, guys. Thanks for taking our question and congrats on the progress. So, now that 5051 seems out, are there any thoughts for lifecycle management of the PMOs? And it kind of feels like Sarepta is strategically moving away from Exon skippers. Thank you.

First, I don't want to suggest for a moment that we're moving away from Exon skippers. And we do have a lot of thoughts on other modalities for Exon skipping. We're not in a position right now to discuss them in any detail, but we are constantly looking at opportunities to enhance the benefit that, that our therapies provide to patients. The reason that we're not moving away from Exon skipping right now, even though we are very excited both about ELEVIDYS and what ELEVIDYS can do, but -- and also the rest of our deep pipeline, including cardiomyopathies and CNS and other neuromuscular as well, the reason we're still excited about PMOs is they're doing an enormous amount of good right now. Okay? So -- and that's an important thing to consider. The PMOs make a small amount of dystrophin, but a small amount of dystrophin is very meaningful. As we have recently published the real-world evidence on EXONDYS, which will presumably be the same answer for VYONDYS and AMONDYS over time as payers experience are really tremendous. We're seeing multiple years out of a wheelchair, multiple years better mortality, multiple years off event reductions in emergency room visits and the like. So we remain very excited about the benefit that our PMOs can safely provide to patients. And that's one of the things that's really great about the PMOs and that is that they not only are providing a really significant benefit to patients, but the safety profile is great. And that's why one should remember, even as we think about our own pipeline and we think about others, that while we're always ambitious, the bar for beating the PMOs is very high and the road to any approval for an alternative to our PMOs on the Exon skipping side is very long. So, I don't want to suggest for a minute that we're in any way less excited about our PMOs. We're excited every week that a patient gets an infusion and benefits from either EXONDYS or VYONDYS or AMONDYS, and we will remain that way. And I think one of the things that I'm excited about right now, particularly during the launch of the fact that we're not seeing a ton of cannibalization, is that there is a long road for the PMOs, and I think they're going to be very durable.

Thank you. And one moment for our next question. Our next question is going to come from the line of Ritu Baral with TD Cowen. Your line is open. Please go ahead.

Hi, guys. Thanks for taking the question. I wanted to ask about forward guidance, especially given the insight you guys have on basically revenues. Doug, you mentioned, three to five months time to fill. And just given where you guys are notified about when a patient is seeking reimbursement and when you have to make their kit, ship the kit, et cetera, and when they're dosed. Are we going to -- one, are we going to continue to get some pretty granular guidance as you've given, and two, given the healthy beat, congratulations this quarter. What sort of swing factors should we be thinking about despite that three to five-month insight? Logistical swing factors beyond Ian's tendency to give conservative guidance.

Look, of course, it's always our goal to provide reasonable and accurate guidance, but guidance that we're very comfortable with and we will continue to ensure that we are comfortable with the guidance that we provide. And if that makes us seem conservative, I'm probably proud of that. We have an enormous amount of insight, as you know, about not only broadly about Duchenne muscular dystrophy and EPI in prevalence, but all the way down to things like start forms and the like. And that does provide us with a lot of confidence as we think about forecasting and guidance and the like. And with that said, as we sit here today, notwithstanding are very, very positive, in my view, and significant beat, we're going to -- we're not going to update our guidance at this moment. And we'll talk again probably at JPMorgan if we do preannounce at JPMorgan about 2025.

Thank you. And one moment for our next question. Our next question comes from the line of Joe Schwartz with Leerink Partners. Your line is open. Please go ahead.

Great. Thanks very much. I have a question about the next MRI study you plan to do. I'm wondering how will this differ from the MRI data that you presented at WMAS [ph]? And will you be using gadolinium enhancement to evaluate tissue characteristics like edema and fibrosis periodosing and will you evaluate global longitudinal strain?

Louise?

Sure. So, from the EMBARK study, the longer term data will be following the patients over time and then that will be compared. There's a wealth of natural history data compared to natural history since all patients have been dosed now, so they'd be compared to their baseline and then to natural history. So, we'll continue to do MRI, MRS and T2. T2 gives the early signal of the inflammation and edema that you noted. So that's a precursor to changes that you would see by MRI and MRS. So we'll continue to use those three measurements and strain is a portion of the MRI result.

Thank you. And one moment for our next question. Our next question comes from the line of Kostas Biliouris with BMO Capital Markets. Your line is open. Please go ahead.

Hi, everyone. Thanks for taking our questions and congrats on the quarter. One question from us on manufacturing. Given the 300% quarter-over-quarter growth of ELEVIDYS sales ex-US and potential further acceleration with upcoming approvals in Europe and Japan, can you comment on your manufacturing capacity to meet this high level of demand? And a follow up on the same topic, can you clarify whether the suspension manufacturing will be only with Thermo Fisher or there is optionality to do that with Catalan [ph] as well? Thank you.

Yeah. Thank you very much for your questions, Kostas. First, as relates to the first part of your question, we're very comfortable with our forecast and our manufacturing to supply. We're in a very good position from a manufacturing perspective to serve ours and our partners' needs. As relates to suspension, to remind everyone things are going very well with suspension. Right now, we're in engineering runs both in 500 liter and 2,000 liters and we're going to start our bridging steady next year assuming everything goes well and we believe it will. And we have not made a decision as it stands today on who we will use as a commercial supplier for suspension. So that's an issue we're continuing to ponder and evaluate.

Thank you. And one moment for our next question. Our next question comes from the line of Brian Skorney with Baird. Your line is open. Please go ahead.

Hey, good afternoon, everyone and thanks for taking my question. Actually my question is on redosing, I guess when should we think about seeing initial data here from either the apheresis study or the Hansa collaboration study you're planning to go about? And how do you kind of think about clinical development here? Do you focus on patients who had received prior ELEVIDYS but had inadequate dystrophin response? Do you target naive patients with higher rh74 serology? And do you have access to just Imlifidase in your Hansa deal? Or is HNSA-5487 their next gen cleaver included in that? Thanks.

All right. I'm going to turn this to Louise. Before I do, I want to make sure I have a clarification here. And Brian, thank you very much for your question and the opportunity to clarify. So, there is definitely an opportunity down the road to use some modality to either cleave or clear neutralizing antibodies in a manner that might allow for redosing. And we're very excited about that potential. But just so we're clear as we sit here today, that is not actually the goal of our near-term studies. Our near-term studies are intended to do something slightly different, which is to clear or cleave antibodies that have been acquired by a Duchenne patient through environmental exposure to put them in a position where we could dose them with a ELEVIDYS. And that would provide an opportunity for another 15% or so of Duchenne patients who would right now be screened out to actually get the opportunity to have a ELEVIDYS. And with that, Louise, if you want to provide some color on Brian's questions.

Sure. So, the question about when we'll have data for both studies, we'll have safety and expression data in early 2025 on the initial cohorts. And really that data will inform us for anything we do in the future with regards to a potential study for redosing. As Doug mentioned, that's not the goal right now, but we've been positioning ourselves to be ready in case we do. We've shown good data in non-human primates. So the challenge for redosing is much higher antibody levels. And so, this data from these preexisting antibody charts will be critical in seeing how far we can go and how we might design a study if we were to do so with three dosing.

And then, Brian, to answer your final question, we have a right of first negotiation on a next generation therapy.

Thank you. And one moment for our next question. Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Your line is open. Please go ahead.

Hi. Congratulations on the revenue beat. You seem to not be getting a whole lot of credit for the limb-girdle portfolio. So, I wanted to ask if you could remind us about the number of patients you expect could be identified around the time of these launches and how we should be thinking about that market opportunity. Thank you.

Yeah. That's a great question. Thank you very much. And it's a particularly poignant question now because we're really starting to make traction and move fast on our limb-girdle portfolio. Broadly speaking, let me say that the limb-girdle portfolio that we have today is about 70% of the opportunity of Duchenne muscular dystrophy. So quite significant. And if you think about the size of Duchenne muscular dystrophy, maybe in the 12,000 to 15,000, probably more like 12,000 range in the United States, then you can see this is a massive opportunity to do good and do well by our investors at the same time. Our near-term program, sarcoglycan, are themselves actually quite significant. They're something in the range of 25% or more of the Duchenne muscular dystrophy. And we're going to be in late-stage development with all three of those programs in the coming few months. So, it is a big opportunity that I think people will start focusing on as they clear and get more excited about and more confident about the launch of ELEVIDYS. And hopefully this quarter has helped them do that.

Thank you. And one moment as we move on to our next question. Our next question comes from the line of Biren Amin with Piper Sandler. Your line is open. Please go ahead.

Yeah. Hi, guys. Thanks for taking my questions. Can you maybe just talk about the split of patients that you saw in the third quarter across ambulatory versus non-ambulatory from a commercial standpoint? And what type of access are you seeing across both groups? Thanks.

Yeah. We're not going to provide a granular breakdown of that, but I can give you some broad qualitative color. One of the things that one would anticipate that we anticipated and others have anticipated at launch is that there may be a bias in favor of ambulatory patients over non-ambulatory patients at launch. And certainly, that is the case, but isn't probably as significant as some may have imagined. We're seeing a very significant percentage of start forms for late ambulatory, non-ambulatory patients, which is fantastic. I think that as more information comes out about the number of patients that have been dosed in the late ambulatory, non-ambulatory setting and the safety profile that we're seeing there, which is the same as the ambulatory patients, it's only going to increase that awareness and excitement. We've already dosed kids in the mid-20s who are obviously non-ambulatory and we have start forms of men in their late 30s which is very, very advanced for Duchenne muscular dystrophy. So while there is, as we have guided to and anticipated, there is some bias towards the ambulatory versus non-ambulatory in the very early days. There is a very significant percentage of non-ambulatory and we're quite confident that's going to continue to increase over time. Dallan, is there anything else about that that I've missed?

No, not at all. And just to add, it's not really going to fluctuate quarter-to-quarter. As you had said, that bias towards the ambulatory population kind of in the early going stages of the launch. But we don't expect much fluctuation in that breakdown from quarter-to-quarter. So thanks.

Thank you. One moment for our next question. Our next question is going to come from the line of Gavin Clark-Gartner with Evercore ISI. Your line is open. Please go ahead.

Hey, guys. Thanks for taking the question. I just wanted to ask on the ESSENCE confirmatory trial, is the latest guidance still for data in 2026? I'm just looking at the trial page and it still notes the primary completion date is next week actually. And just more broadly for this trial, do you have any sense what the requirements to actually pull these drugs off the market? Maybe especially in light of the fact we haven't really heard anything following the Viltepso results. Thanks.

Well, first of all, Louise, correct me if I am wrong, the readout for ESSENCE is in 2026, correct?

That's correct.

Yeah. And then as it relates to the standard, the standard for evaluating a therapy and whether it, should be removed from the market is based on the totality of evidence. When all of the evidence is in on the therapy, the FDA will look at the totality of all of the evidence associated with that therapy, including study results, including trends in the study results, including presumably information like the real-world evidence that we've gathered with respect to the PMOs, which has been very positive so far. And then we'll make a decision. It won't be a yes or no based on one single trial. That isn't the standard.

Thank you. And one moment for our next question. Our next question is going to come from the line of Leo Watson with Mizuho. Your line is open. Please go ahead.

Hi, this is Leo on for Uy. Congrats on the strong quarter and thanks for taking our question. How are you thinking about the competitive dynamics in the Exon skipping business given the recent competitor data readouts and the discontinuation of the PPMO? And while you expect no material cannibalization through '25, we're just curious on how you're thinking about cannibalization going forward in the long-term. Thanks.

Let me answer the second question first. So we don't think we'll see net cannibalization over the course of 2025. Remember, we also have ex-US sales of the PMOs and those won't be in the near term at least subject to any cannibalization. We do model cannibalization after '25. How significant, if at all that will be is something we're going to watch and monitor. But we have some reason to believe that these therapies are going to be very durable, certainly on a net basis over this entire decade. But we'll see how that goes post '25. As relates to competition, I should note that we're not very focused on competition. Right now, there is no one near us today either on the PMOs or certainly on ELEVIDYS. And I will not comment on other folks' programs and I wish them well. One of the things I do want to point out as it relates to the PMOs is that how much good those PMOs are doing today. There was an open issue about that perhaps in late 2016 when EXONDYS was approved, Eteplirsen. But the real-world evidence has been really supportive. You can see it in the compliance rates for these therapies. They're doing an enormous amount of good with a really, really laudable safety profile. And so, the one thing I would say is that when we think about the PMOs and we think about competition, one ought to remember that thus bar to overachieve from both an efficacy and safety perspective for the PMOs is a very high bar. And the road for even getting to clinical data that would allow one to think about approval is a very long one. This is not -- this requires one to go Exon by Exon over a very long period of time. So, I wish these folks well. I think that they have a high bar and a long road to get to the right place.

Thank you. One moment for our next question. Our next question is going to come from the line of Sami Corwin with William Blair. Your line is open. Please go ahead.

Hi, there. Congrats on the quarter and thanks for taking my question. Looking ahead to a potential launch in limb-girdle, do you expect any synergies between LGMD and ELEVIDYS in terms of sales reps or treatment centers? And then with the discontinuation of 5051, could any cost savings there be used to accelerate the development of any of those limb-girdle programs? Thanks.

Well, there's in a way a yes and a yes to both of your questions. Is there synergy between the limb-girdle launch and what we've done with ELEVIDYS? 100%, absolutely. It's going to be very, very synergistic. There'll be nuanced things we need to do in advance to make sure we're very successful. But we have a very seasoned group of folks that know how to service the rare disease community and the neuromuscular community and gain access and reimbursement and to focus on distribution. It's a fascinating thing to consider that the group that launched EXONDYS back in late 2016 that have become so expert, 80% of those folks remain here with Sarepta today. So, yes, there'll be a lot of really nice synergy and really, frankly, synergy at the therapy level as well. I would remind folks that these limb-girdle programs that we're talking about share the same capsid. So, they will really be standing on the shoulders of the safety profile of ELEVIDYS and the same promoter as ELEVIDYS. So the productivity of these therapies is standing on the shoulders of ELEVIDYS. And then as it relates to 5051, I don't want to suggest that we can accelerate the plans based on the cost savings from 5051 only because we're already doing everything we can to move these as fast as possible. And you're seeing it in the progress that we've made and announced in this earnings call. But certainly, there will be some cost savings from 5051 that we get to use to focus back down into research and development and advance our program, including our pipeline, which we're very excited to talk about next year.

Thank you. And one moment for our next question. Our next question comes from the line of Mike Ulz with Morgan Stanley. Your line is open. Please go ahead.

Hi, this is Rohit on for Mike. Thanks for taking our questions. Since we're at the inflection point for ELEVIDYS sales, can you provide any color on early 4Q trends and how they're tracking versus expectations? Thanks.

We're not going to do that right now. We sort of reiterated the guidance that we provided previously. Notwithstanding that some appear to have criticized us for being conservative. We are very -- we are standing by our guidance for Q4 and we are reiterating our guidance for 2025, which I would remind you is a very significant $3 billion, two-thirds of which will come from ELEVIDYS and one-third of which will come from our four, our three approved PMOs. So we're feeling very good about where we are as an organization and very consistent with all of our internal forecasts over the last year or so.

Well, thank you all very much for your very insightful questions and for spending time with us this evening. We've had a very positive quarter from our perspective. The ELEVIDYS launch is going swimmingly. The PMOs are performing very well, and we're really starting to see a lot of traction in our pipeline and we're getting very excited about our pipeline generally, but we're very excited about our late-stage limb-girdle programs as well, which are moving into what will be clinical trials that can support the approval of those therapies as well. And as one commenter made today, and I agree with, I don't think there has been enough attention spent on the limb-girdles or the opportunity there both to do good for some patients who really need us and do well by the investors who stand by us. I look forward to keeping you all up to date and talking to you about the fourth quarter performance when we announce fourth quarter performance next year. Thank you all very much.