Good afternoon, and welcome to the Sarepta Therapeutics First Quarter 2025 Financial Results Conference Call. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Mary Jenkins, Associate Director, Investor Relations. Please go ahead.

Thank you, Marvin, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2025. The press release, slides, and supplementary information are available on the Investor section of our website at sarepta.com, and our 10-Q was filed with the SEC 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 refer to Slide 2 on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta'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 SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. As noted on Slide 3, we will discuss non-GAAP financial measures on this webcast. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available in the Investors section of our website. 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, everyone, and thank you for joining Sarepta Therapeutics' first quarter 2025 financial results conference call. Across biotech and indeed the market more generally, the first quarter of 2025 has been a challenging one. Likewise, for Sarepta, we have faced challenges that have motivated us to take a more measured view for the remainder of 2025. Fortunately, Sarepta is in a better position than most of biotech today, as we have a significant number of approved therapies, significant revenue, a strong P&L, a balance sheet, and the ability to continue to independently drive our portfolio of gene therapies and siRNA programs. We are well positioned to weather this chaotic period. In the first quarter of 2025, we achieved $612 million in total net product revenue, representing 70% growth over the same quarter last year. Our PMO franchise grew 5%, achieving $237 million for the quarter, and ELEVIDYS achieved sales of $375 million in the quarter, representing a 180% increase over the same quarter last year. While our ELEVIDYS first-quarter growth still represents the most successful in vivo gene therapy launch in history, in fact, in Q1, we treated more patients with gene therapy than ever before in the US in a single quarter; we nevertheless fell short of expectations. In a moment, Dallan will explain some of those quarterly factors, including administrative issues, a severe flu season that resulted in delays, and the effect of the recently reported safety event that motivated some families with scheduled infusions to pause for additional information. Looking forward, we are changing our net product revenue guidance for the year to $2.3 billion to $2.6 billion across our four approved therapies. This change is driven by three factors. First, as you know, we recently reported that a boy infused with ELEVIDYS suffered an acute liver failure and passed away. This was an unimaginably tragic event for that family who, with ELEVIDYS, finally had reason to hope for a brighter future for their son. At Sarepta, we are deeply committed to the patients we serve. This event, markedly different from all other experiences with ELEVIDYS, was heartbreaking for all of us. While it is of no comfort to the family involved, it's important to remember that more than 800 patients have been infused with ELEVIDYS. The outcome of this event is inconsistent with all other experiences with ELEVIDYS, and we are continuing to explore what was uniquely different about this case compared to all the other hundreds of infusions that have occurred to date. What we do know is that while this young man's outcome was surprising, this did not represent a new safety signal for AAV-mediated gene therapy generally or ELEVIDYS more specifically; nor did it change the positive risk-benefit of ELEVIDYS, which has had a stable and commendable safety profile in the context of AAV-mediated gene therapy since first being infused back in January of 2018. Of course, to support optimal outcomes, we have always prioritized patient safety. We have proactively placed significant monitoring requirements in our label. We require all sites to complete training before being permitted to treat, and we have a never-before-seen program called SAREPTA EXCHANGE that provides physicians with near real-time access to the leading experts around the world so that outcomes are consistent across the country. We also provide education for our patient community and are committed to providing timely information about this life-enhancing therapy. What we have observed is that top thought leaders who understand the data have not changed their treatment approach, and informed families understand the positive risk-benefit of ELEVIDYS. However, there will be an impact on infusions as we roll out education in the broader physician community and families gain better insight into the profile of this disease-modifying therapy and have their questions answered. Second, as we have discussed, the administrative process from start form to infusion is particularly complicated for gene therapy. It includes, for instance, more appointments, more screenings, and steps like single-case agreements, far more than other therapies. As we launched the broader label and expanded the actual cadence from start form to infusion is taking about one month to six weeks longer than our original estimates, informing our forward forecasts. For the avoidance of doubt, this is not about ultimate access but the administrative steps to get infused. As we know, we are quite proficient in working with sites to gain access. In fact, for our PMOs, our ultimate rate for gaining payer access has been well over 90%, and for ELEVIDYS, it currently remains at 100%. We are taking actions to shorten that turnaround time. There are some reasons to believe that our first quarter experience, which includes illness-related delays and the typical first-quarter insurance changes that can cause delays, may have been longer than steady state. However, for purposes of setting guidance for the year, we are assuming our first-quarter experience on turnaround times is representative of the year as a whole. This will have a significant timing impact on infusion and hence a significant impact on revenue in 2025. Finally, the success we have seen with top sites has caused an imbalance that we need to address across this year. Sixty percent of our current revenue comes from top sites and top thought leaders. Their experience and enthusiasm for ELEVIDYS have resulted in many of them being fully booked out to 12 months. We need to direct much of our attention going forward to sites with more capacity. We do not take lightly our decision to change guidance. Given the environment and some of the constraints we are working to address, we do believe it prudent. What we do know is this: ELEVIDYS is the first and only available disease-modifying therapy that offers the possibility of arresting further muscle damage in 80% or more of patients being daily damaged by Duchenne muscular dystrophy. It is a disease-modifying therapy that restores significant amounts of a form of muscle-protecting dystrophin and has observed over multiple studies, over eight years of clinical experience and clinical evidence in hundreds of patients of data; it is the only gene therapy proven to preserve function in boys dying from Duchenne. Without intervention every day, the muscle of boys with Duchenne is destroyed and permanently replaced by fat and fibrotic tissue. With the FDA following the positive expert advisory panel and approving ELEVIDYS broadly for boys with Duchenne, families finally now have a chance to choose a different journey. Now that a disease-modifying therapy is finally available to them, if families are delayed in getting a therapy that can finally protect them from Duchenne's relentless damage and they are delayed either because of administrative issues, other delays, a lack of information, or even at times circulating misinformation, then we will have failed in our mission. I hope we have proven repeatedly over these last eight years, and we do not intend to fail in our mission. After our Chief Customer Officer, Dallan Murray, provides an overview, we will hear from our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac. She will speak to you about the continuing evolution of data for the impressive efficacy of ELEVIDYS and our plans to expand even further the population of patients who will have access to ELEVIDYS. Finally, Dr. Rodino-Klapac will provide an overview of the great progress we are making on our LGMD portfolio and we'll discuss our progress with our siRNA platform, including our plan to share our proof of biology and proof of concept data from both our FSHD and DM1 programs in the second half of this year. And with that, let me turn the call over to our Chief Customer Officer Dallan Murray. Dallan?

Thank you, Doug, and good afternoon. My comments today are focused on three areas: context for what happened in Q1, how we plan to achieve our revised full-year guidance for 2025, and what gives us confidence in our ability to achieve that guidance. Regarding our Q1 performance, in addition to the safety event, there were two issues that impacted our results late into the quarter. Firstly, the severe flu season caused a number of patients to delay their infusion dates. Secondly, we faced administrative issues at some sites, the most impactful of which was with Medi-Cal, California's Medicaid program that pushed out patients' infusion dates. Importantly, these specific administrative challenges have now been successfully resolved. Now, I'll outline how our first-quarter performance informs our revised guidance and the actions we'll take. First, the safety event led some patients and families scheduled for late March dosing to delay treatment while they sought more information. We immediately initiated extensive outreach to our leading treaters in the broader community. Conversations have revealed that access to comprehensive safety data, including our biomarker safety data, which Louise will discuss in her prepared remarks, in conjunction with the two-year EMBARK data provides the necessary context for health care providers and patients to move forward with confidence. Our current focus is on disseminating this information across the wider treating and referring physician landscape, which is a process that takes time. As a result, we anticipate Q2 revenue could be as much as 20% lower than Q1. Looking ahead, we project a pickup in demand beginning in the summer and extending through the remainder of the year. Therefore, our long-term demand outlook for the therapy remains strong, and we expect only a temporary impact. Furthermore, we are encouraged that we continue to receive enrollment forms for both ambulant and non-ambulant patients. Secondly, as we discussed, the administrative path for gene therapy from initial paperwork to infusion is inherently complex, involving significantly more appointments, tests, and steps than typical therapies. However, with the broader label and our expansion to a wider range of patients, the actual start form to infusion cadence is extending by 1 to 1.5 months beyond initial estimates. This longer duration is primarily attributable to more rigorous screening protocols implemented to ensure patient safety within this expanded population, coupled with the intricate logistical requirements at the site level, including the navigation of single-case agreements with payers. We are actively working with individual sites to create more efficiencies and less delay and have developed comprehensive tools for families to help navigate the journey. But while we are working to shorten turnaround times, we are nonetheless taking a conservative approach and incorporating the longer Q1 turnaround into our revised 2025 guidance. Thirdly, regarding site capacity. We observed a dichotomy across our network. While our total network capacity is robust, our most established and recognized treatment sites are facing substantial demand, resulting in appointment lead times approaching a year due to near-full operational capacity. Simultaneously, a significant number of treatment centers across the country have the potential to increase their patient volume and contribute more significantly to our reach. Our strategy involves a proactive approach to engage these centers more deeply through enhanced high-touch support like we have done with the leading treatment centers. This focused effort, bolstered by the encouraging two-year clinical data we highlighted earlier, is generating positive momentum in expanding our site engagement and our overall network utilization. Lastly, our teams are now intensifying their efforts to promote the deep and impressive evidence for the benefits of ELEVIDYS. We launched our comprehensive healthcare provider and patient promotional campaign in the first quarter, which includes a fully built-out elevidys.com website and significant direct-to-consumer investment through digital channels designed to drive awareness and understanding. With focused work already underway to address these three key areas—education, tightening turnaround times, and site capacity optimization—we have a clear path forward to effectively support the patient community and achieve our revised guidance. Taken together, we firmly believe that our collective efforts are guided by the critical principle that time is muscle and will ultimately result in more patients gaining access to our therapy faster. The fundamental size of the opportunity remains unchanged, and we are resolute in our intention to reach every eligible patient and continue to change the course of this devastating disease. Thank you for your attention today. And with that, I would like to hand over the call to our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac. Louise?

Thank you, Dallan. The role of science in transforming patient lives has never been more important than it is at this moment. At Sarepta, science is foundational to who we are. I'll focus my comments today on three areas: ELEVIDYS, including additional data that supports safety and efficacy; the progress we've made in advancing our limb-girdle portfolio, solidifying our scientific leadership in neuromuscular diseases; and the momentum behind our siRNA therapies, including the opportunity they hold to be best in class. Further, we are excited to share the depth of our research at our upcoming R&D Day later this year. This work will fuel future innovations to treat diseases for which therapies are either nonexistent or inadequate. Beginning with ELEVIDYS, we provided data to the FDA, and we'll continue to work with them on any necessary updates to the ELEVIDYS label or monitoring requirements. Safety remains our top priority and as we have these past weeks, beginning at MDA, we will continue to ensure that our community stakeholders are informed in a timely manner and that we address their questions. Regarding safety, in patients treated with ELEVIDYS, we see no difference in the rates of adverse events related to age or weight. Furthermore, no relationships have been identified between the liver safety biomarkers, bilirubin, GGT and INR and the total dose administered for patient age or patient weight. Shown on this slide are bilirubin values versus all cohorts in Study 103 and EMBARK. Regardless of whether it's change from baseline, absolute peak, or peak value, there is no correlation with weight or age. The same holds true for cardiac safety biomarkers, including troponin. The totality of our data in over 800 patients support the safety of ELEVIDYS weight-based dosing across the label population of patients with Duchenne, regardless of ambulatory status. Life cycle development for ELEVIDYS continues to progress, highlighted by multiple activities. Starting with ENVISION, our post-marketing commitment trials for ELEVIDYS. ENVISION is a Phase 3 global placebo-controlled trial in older ambulatory and nonambulatory individuals with Duchenne and has progressed well. In the United States, enrollment is complete, and we continue to dose outside the US. Our last patient visit is expected in 2027 following an 18-month placebo-controlled period. Next, for AAVrh74 antibody-positive patients, we are conducting two studies, Study 104 with imlifidase to cleave antibodies and Study 105 to remove antibodies with plasmapheresis. We expect to have expression and safety data from both of these studies in the second half of 2025. We continue to advance our understanding of ELEVIDYS and publish and share these scientific data in support of the DMD population. The evidence continues to build supporting the safety and efficacy of ELEVIDYS, particularly as time progresses as compared to natural history. In that spirit, we shared important updates at this year's MDA meeting, including results from our two-year EMBARK and three-year pooled analysis, indicating stabilization or slowing of disease progression compared with well-matched external control assessed by functional outcomes predictive for delaying loss of ambulation. At two years, EMBARK Part 1 ELEVIDYS-treated patients demonstrated statistically significant and clinically meaningful functional benefit in NSAA total score, time to rise and 10-meter walk run versus a propensity score-weighted external control cohort. In addition, as previously mentioned on last quarter's call, the muscle MRI data we observed showed minimal progression in underlying muscle pathology in ELEVIDYS-treated patients, underscoring the importance of treating as soon as possible to preserve muscle. Lastly, we're looking forward to sharing additional data from the EMBARK study at this year's ASGCT's annual meeting this month in New Orleans, Louisiana. Moving now to our program for limb-girdle muscular dystrophies, or LGMDs, each of the LGMD programs builds on our experience with ELEVIDYS. We use the same vector, rh74, in both ELEVIDYS and our LGMD programs, which has a differentiated safety profile and high transduction efficiency. To this end, we've requested a platform technologies designation to enable leveraging of shared technology and future applications. We were thrilled to announce in December 2024 that we completed enrollment and dosing from study SRP-9003-301 for EMERGENE. Our Phase 3 clinical trial SRP-9003 to treat LGMD type 2E or beta-sarcoglycanopathy. EMERGENE is a global study and the primary endpoint is biomarker expression of the beta-sarcoglycan protein. A pre-BLA meeting has occurred and the Office of Therapeutic Products or OTP has confirmed eligibility for the accelerated approval pathway for this program. Due to the similarities between ELEVIDYS and SRP-9003, we have agreed to leverage ELEVIDYS data for the SRP-9003 BLA. Sarepta remains on track to submit a BLA to the FDA in the second half of 2025. We are also encouraged by the progress of our other LGMD programs. Just last month, we announced that we completed enrollment in dosing for study SRP-9004-102 or our DISCOVERY study. DISCOVERY is a Phase 1 proof-of-concept study evaluating safety and expression of the alpha-sarcoglycan protein after treatment with SRP-9004. SRP-9004 is in development to treat LGMD type 2D or alpha-sarcoglycanopathy. We plan to initiate a Phase 3 trial before the end of the year. Also last month, we announced the following input from OTP; we were cleared to proceed with study SRP-9005-101 for our COMPASS study in the United States. COMPASS is a first-in-human clinical study of SRP-9005, which is in development for the treatment of LGMD type 2C or gamma-sarcoglycanopathy. As a reminder, with support from the agency, we adopted a Phase 1/3 seamless design clinical trial for SRP-9005, with the aim of facilitating a more efficient and faster path to BLA. We also look forward to highlighting our impressive pipeline and research at an upcoming R&D day in the latter half of 2025. As a preview, we have numerous programs in various stages of development across neuromuscular, central nervous system, cardiac, and pulmonary indications. Many of these programs are nearing IND. On the research side, we've continued to innovate across platforms, developing new AAV capsids as well as driving innovation in gene editing and enhanced delivery for RNA. The momentum around our other programs continues. We look forward to sharing data with you later this year around our FSHD1 and DM1 programs. Beyond the multiple high-value catalysts to come this year and into the coming years, our siRNA programs leverage Sarepta's successful track record in developing and commercializing neuromuscular therapies, while also expanding our portfolio into CNS and pulmonary therapies and broadening our focus into chronic therapies alongside onetime therapies. SRP-1001 is currently in clinical development to treat FSHD1, and we are encouraged by the nonclinical data generated thus far. Cohort 2 in the SAD study is now fully enrolled, and we look forward to the data readout later this year. Turning to myotonic dystrophy type 1, or DM1, Cohort 1 in the SAD study is now fully enrolled, and we look forward to sharing the data from that study later in the year. Now to discuss our PMO platform. The ESSENCE trial, our post-marketing requirement for golodirsen and casimersen, as well as mission for post-marketing commitment for EXONDYS, are both fully enrolled and remain on track. We look forward to sharing data as soon as these studies are completed and continue to collect and publish real-world data on the long-term effects of our PMO. In closing, I'd like to take this opportunity to thank my Sarepta colleagues and those in the patient and clinical community. For those of us in the field of genetic medicine, the work continues, and good science will always prevail. We must scrub the opportunities before us because patients are waiting. I'll now turn the call over to Ian for an update on the financials. Ian?

Thanks, Louise, and good afternoon, everyone. This afternoon's financial results press release provided details for the first quarter of 2025 on a GAAP basis as well as a non-GAAP basis. Please refer to our press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results. Beginning in the first quarter of 2025, the gains and losses on mark-to-market of strategic investments are excluded from our non-GAAP results. For comparison purposes, non-GAAP financial results for the first quarter of 2024 have been updated to reflect this change. In Q1, we delivered strong year-over-year growth in revenue, continued disciplined approach to investment in R&D and SG&A, and maintained our strong cash position with $647 million in cash, cash equivalents and investments and restricted cash as of the end of the quarter and $600 million of additional liquidity available through our revolver. The decrease in our cash balance from last quarter was due to the funding of the Arrowhead collaboration upfront consideration of $825 million with cash on hand. Note, we have reported a Q1 GAAP and non-GAAP operating loss of $300 million and $250 million, respectively, both included a $584 million of R&D expense associated with our global licensing and collaboration and stock purchase agreement with Arrowhead. Excluding this transaction, we are reporting a GAAP and non-GAAP operating profit of $283 million and $334 million, respectively. In the first quarter, we delivered $612 million in total net product revenue, representing year-over-year growth of 70%. ELEVIDYS net product revenue was $375 million and grew 180% year-over-year, and net product revenue from our PMO exon skipping franchise was $237 million, up 5% over the prior year. In Q1, we recognized $133 million of collaboration and other revenues. This primarily reflects $112 million of collaboration revenues related to Roche expired options of a certain program, as well as $17 million of contract manufacturing revenues for sales of commercial ELEVIDYS supply to Roche. The reimbursable co-development costs under the Roche agreement, which is recorded at the contra operating expense totaled $29 million in Q1 compared to $22 million for the same prior year period. Total revenues were $745 million in the first quarter and increased $331 million, or 80% year-over-year. Q1 cost of sales totaled $138 million compared to $51 million in the same period of '24. The increase was driven by an increase in ELEVIDYS sales, as well as an increase in cost of sales related to products sold to Roche. Now moving to our R&D expenses. On a GAAP basis, we recorded $773 million and $200 million in R&D expenses for the first quarter of 2025 and 2024, respectively, a year-over-year increase of $573 million. The increase is primarily due to the $584 million upfront and milestone expenses associated with the aforementioned Arrowhead collaboration. On a non-GAAP basis, R&D expenses were $749 million for the first quarter of 2025 compared to $178 million for the same period of 2024, an increase of $571 million. Now turning to SG&A. On a GAAP basis, SG&A totaled $134 million, up 5% year-over-year. This increase was primarily driven by an increase in compensation and other personnel expenses and higher sales and marketing spending to commercialize ELEVIDYS. On a non-GAAP basis, SG&A expenses totaled $107 million, up 7% year-over-year. On a GAAP basis, we recorded an $83 million charge in other expenses net in Q1 '25. This was primarily due to the loss on strategic investments, which includes recurring fair value adjustments of investments of publicly traded companies, including Arrowhead. GAAP income taxes were $64 million in the quarter compared to $5 million in the prior year. The increase is driven primarily by increased taxable profit, largely due to ELEVIDYS revenues. Also on a GAAP basis, we reported a net loss of $448 million or $4.60 per basic and diluted share for the first quarter of 2025. We reported a non-GAAP net loss of $332 million or $3.42 per diluted share. Now, turning to our outlook for 2025. As mentioned earlier, we are revising our total product revenue guidance to $2.3 billion to $2.6 billion. This still represents a 37% increase from our 2024 total product revenue at the midpoint. Our PMO guidance remains the same at around $900 million. Our combined 2025 non-GAAP R&D and SG&A expenses, excluding the impact of the Arrowhead collaboration upfront transaction expense and potential DM1 development milestones, remain at $1.2 billion to $1.3 billion. However, we anticipate to be at the closer to the low end of the range. With our undrawn $600 million revolving credit facility, we are in a strong position to further invest in internal and external innovation and to support our capital allocation strategy. We believe our recent share price levels do not reflect the current value of the company today nor the growth potential we expect to achieve in the future. As such, we remain opportunistic and disciplined within our capital allocation strategy to deliver value to our shareholders while also preserving financial flexibility to invest in our long-term growth opportunities. We remain well-positioned for the future with four approved therapies generating significant revenue and revenue growth, and we remain committed to sustained profit, operating expense leverage, and positive cash flow for the remainder of the year. And with that, I'll turn the call over to Doug to start the Q&A. Doug?

Thank you very much, Ian. Marvin, let's open the line for Q&A.

Our first question comes from Tazeen Ahmad of Bank of America Securities. Your line is now open.

Hi, guys. Good afternoon, and thanks for taking my question. So, Doug, I just wanted to ask you, on those three factors that you mentioned right at the beginning of the call, the capacity issues, the administrative processes that you mentioned, and the results of the patient death, leaving families to have questions, which one, if any, has been the biggest driver of potential downside pressure leading you to revised guidance? And then as 2Q has progressed, have any of those I guess, gotten worse because you're talking about 20% lower sales relative to 1Q, and we're still pretty, I guess, relatively early into the quarter. Thanks.

Thank you for your question. First, regarding the balance, it includes a combination of all three factors. I believe the cycle times are the primary mechanical factor affecting our forward guidance. However, the situation is not deteriorating. We don't currently have sufficient data on the cycle time issue to indicate that we are overly conservative, but we are at least confident that we have reached a steady state. There may be a reason to think that our assumptions might be slightly conservative. As I mentioned earlier, the first quarter experienced the most severe flu season in 15 years, which led to some delays. Additionally, the typical changes in insurance during the first quarter cause further delays. It’s possible that the four to six weeks of extra cycle time we are seeing could be linked to these first-quarter issues. For planning purposes, we are assuming, and I believe you should also assume, that we have reached a steady state for the year. We have a lot of work ahead of us, and we aim to operate even more efficiently, although we shouldn't assume we will achieve this automatically. Regarding the safety event, it's important to note that it occurred right before March, just before the last month of the quarter. Consequently, those who required additional information faced delays, which will also impact the second quarter. It shouldn't be surprising that the second quarter appears to be softer as a result. It will take time to address this, and we need to engage with the broader community. As I mentioned in my prepared remarks, when we meet with key thought leaders—like we did at the MDA conference—it was clear from my interactions that they do not see this safety event changing their prescribing behavior. We receive the same feedback from families; we just need to reach out to more families. Currently, the signals we are observing could be described as early positive indicators, as we are seeing start forms coming in for both ambulatory and non-ambulatory patients. Although I cannot provide a specific breakdown at this moment, we are making progress. As we communicate and educate, we see continued engagement. Over time, the response should not differ significantly between ambulatory and non-ambulatory patients, as the data shows that only a minority experience liver enzyme issues, and these do not occur at a greater rate or severity in non-ambulatory compared to ambulatory patients. Hence, we are seeing positivity when we get out there and educate. We have significant work to do this year to reach those secondary sites where capacity exists. One of our challenges has been our success with the major thought leaders, as those sites are often fully booked. Therefore, we need to connect with other sites to ensure we reach areas with capacity, increase education for both physicians and the broader community, and continue to improve cycle times.

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

Good afternoon, guys. Thanks for taking the question. Doug, I want to follow up on that last phrase that you mentioned, how do you direct patients to those sites with more capacity? Are we talking like more community sites, and why aren't these sites sort of at capacity like the main centers? Is it a staffing issue? Is it a demand issue? How do you plan on doing that? And is this the point where you think about opening more sites?

I believe the current challenge is more about our focus rather than the number of sites. Naturally, when we launch a new therapy, we prioritize larger sites with experienced thought leaders who have a lot of patient involvement. While we've also trained other sites and dedicated time to them, we focus significantly on educational efforts, particularly in response to recent safety events. More positively, we need to promote the impressive data we have from the crossover study. This data shows that children who have been on the therapy for two years outperform the natural history group across every functional measure, even for older age groups where participants are in the decline phase, which poses a challenge for our original NSA-related study. The results are statistically significant across all measures, including NSA. Additionally, the trajectory analysis and muscle MRI findings are noteworthy. Initially, there were doubts about observing significant differences in muscle quality within a year, but the outcomes across multiple muscles are very favorable. Children treated with ELEVIDYS have preserved muscle mass and less fat infiltration compared to those who did not receive the treatment and experienced muscle loss and higher fat infiltration later on. We aim to share this information and foster discussions with the secondary sites. However, it's challenging to simply redirect patients from one site to another. Instead, we can invest our time, energy, and educational resources to help them while also educating the patient community nationwide. I believe this will ultimately yield significant benefits, not only in terms of our revenue but, more importantly, in ensuring more children receive this life-changing therapy. Thank you for your questions, Ritu.

Thank you. One moment for our next question. Our next question comes from the line of Louise Chen of Scotiabank. Your line is now open.

Hi, thanks for taking my question here. I wanted to ask you, of the new guidance you gave, what percent of sales does ELEVIDYS represent? And also, are you planning or expecting that sales will recover starting in the third quarter? Thank you.

So, the—two answers to that. Obviously, we're pulling our guidance down primarily—well, exclusively really from ELEVIDYS. So you can do the math on that. This is an ELEVIDYS related issue. And then yeah, we are assuming starting in the summertime soon, and starting really in the second half of the year that we're going to see a significant uptick. We're already seeing, again, using a hackneyed phrase, the green shoots of that. But what we really do know when we've talked to a lot of physicians is there are a lot of families that prioritize the summer program. There's a lot of monitoring that goes on with this therapy. Lots of times, people have to travel with this therapy. There are other family members and brothers and sisters to be considered. And so we really are expecting and we believe we're going to see a significant uptick starting in the summertime plus the back half of the year as we execute. And we will execute.

Yeah. Very specifically, we gave guidance of $900 million for our PMO. We maintained the guidance of $900 million from our PMO franchise. So, the revision in our total net product revenue was all related to ELEVIDYS.

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

Hi, thanks for taking my question. My question is around this—following this patient death, some investors are wondering about a worst-case scenario where ELEVIDYS is pulled from the market, something more drastic basically than what your revised guidance assumes. The appointment—and the appointment of Dr. Prasad today might not help with that narrative. So, can you walk us through how you think about that potential risk, especially since you do have an accelerated approval in the non-ambulatory DMD? Thanks.

Sure, sure. First, on the appointment, I want to be clear, I'm not going to obviously comment on any particular appointment, which we just got news of today. What I do remain confident about is that the FDA is going to be the FDA that it's been for the last 100 years, which is an organization dedicated to following great science and fulfilling its mission of bringing life-enhancing therapies that are safe and efficacious to patients. There is no reason to believe that that should change or that anyone would permit that to change. I would remind you as it relates to ELEVIDYS, the evidence for its approval was brilliant at the time, absolutely remarkable, and then only got more impressive over time following a positive Advisory Committee meeting. We got the original approval. The totality of evidence was clear that we were changing the trajectory of this disease. And thereafter, we have the crossover data that we unblinded; all prespecified every functional measure was strongly statistically positive, the muscle MRI is brilliant. There’s no doubt that this therapy is changing the lives of patients. There is no reason to believe that this safety event would be the motivator, as an example, for something drastic with this therapy. I would remind you that ELEVIDYS has one of the most impressive safety profiles in the context of AAV-mediated gene therapy that has ever existed. It is true that every AAV-mediated gene therapy comes with a risk of elevated liver enzymes, and in other cases, there have been significant consequences for that. They are rare. With respect to us, they are particularly rare. In fact, this one incident is unique, not only in its outcome but even in the sort of the course of it. There's something very different about it. And it's in the context of AAV-mediated gene therapy. It's in the context of the understanding that there is always a risk of elevated liver enzymes in the vast majority of cases. With this one case being the only exception, they respond very rapidly to a modest increase in steroids and come back down to baseline. So there is no reason to believe that a science-driven organization and science-minded regulators would be considering anything other than the fact that they should be proud that they approve this brilliant therapy.

Thank you. One moment for our next question. Our next question comes from the line of Eliana Merle of UBS. Your line is now open.

Hey, guys. Thanks for taking the question. Just in terms of a potential label update for ELEVIDYS, can you talk us through your latest expectations there for any potential update or conversations with the FDA after the patient death? I guess, when could we potentially hear about a label update and what your expectations are for what this could look like? And then just in terms of the commercial uptake, you mentioned that there were some patients who were scheduled for late March that delayed their dosing. What proportion of those have now rescheduled their infusions? Thanks.

So let me answer the second question first by simply telling you I don't have the data available to me right now. But it was really—those were primarily a function of patients or their physicians who saw the news of the event and needed information. And they're coming up to an infusion in a week. And so they had to either pause or most likely in almost every case rescheduled immediately so they could get access to that information. As it relates to your first question, I will turn the call to Louise, who can provide an update on the label update.

Sure. In April, we submitted a labeling supplement. We already had one planned and anticipated. And so at that time, we also updated the label to include this patient death and the case of ALF. The FDA confirmed receipt of that and set a target review date. So the target completion date will be no later than the fourth quarter this year for those label updates.

Thank you. One moment for our next question. Our next question comes from the line of Brian Abrahams. Your line is now open.

Hi, good afternoon. Thanks for taking my question. Maybe shifting gears to limb-girdle. Following the pre-BLA meeting, have you had any additional meetings with the new FDA leadership on the limb-girdle programs and curious their updated feedback on the accelerated approval path for 2E? And then I guess on 2E, is the emerging data still expected to be disclosed publicly by the middle of 2025 or should we expect that that's going to be initially submitted to the agency? I didn't see anything in the press release or hear anything in your prepared remarks on data. Thanks.

Yeah. I'm going to turn this over to Louise, but let me briefly say the following regarding our interactions with OTP and the LGMD portfolio. So since the change in administration, we have had a number of discussions with OTP and interactions. Everything has remained on course. The approach that they had previously confirmed with us is the approach that they've taken today. So nothing has changed there, which is all very positive. I would also say, I know there's a lot of concern over the fact that the FDA has gone through a lot of dislocation. I think there was an announcement of some 3,500 potential layoffs and that there may be as a result of that delays or slowing down or reviews. But I must give credit where credit is due. We have not yet seen that at all, with our colleagues over at OTP led by Dr. Verdon, Things seem to be quite on track. And certainly, the approach that they were historically taking is the approach they're taking today. But Louise, you're going to want to provide more color about that.

Sure. As we've seen over the past several weeks, we've seen consistent interactions with OTP as we’ve seen previously. We've had a number of interactions. So, on 9003, as noted, they confirmed the accelerated approval pathway is open; just as early as last week, they accepted a rolling review for SRP-9003, so things continue to progress as planned. Also, as we announced, the same review division cleared the IND for SRP-9005 for QC. So, things are progressing as planned with the agency.

Thank you. One moment for our next question. Our next question comes from the line of Debjit of Guggenheim Securities. Your line is now open.

Hey, good afternoon and thanks for taking my questions. So a couple of questions. One on limb-girdle. Is there a threshold for protein expression that the OTP wants to see? And number two, could you sort of quantify the number of non-ambulant boys who have been treated on the commercial ELEVIDYS product? Thank you.

On the second question, we're not providing that level of data, although I will tell you, we've obviously historically been dosing non-ambulatory kids, we're continuing to dose non-ambulatory kids, and we're getting start forms for non-ambulatory kids. On the first question, I will turn that question over to Louise Rodino-Klapac.

Sure. And I think I forgot to answer the question on the previous time about—we will have the emerging data in the first half of this year, which will go into the BLA, that will be expression of esophageal glycan proteins and safety. On the question around expression levels, as you know, from the 101 trial, we saw expression levels with both doses, both the low and high dose around the 50% mark. We know from preclinical data that much lower expression leads to functional benefit. So we anticipate the results that we see from EMERGENE will be consistent with that and will certainly lead to functional benefit and above any threshold of relevance.

And just to add to your first question around the number of non-ambulant patients, I think we have previously disclosed that it's well over 100 patients between the clinical and commercial settings. So we've had good experience there.

I think our enrollment forms, or start forms are something like 40% nonambulatory, 60% ambulatory.

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

Thank you. Good afternoon. Can you remind us as to the timelines for seeing data from your confirmatory studies across both the exon skipping franchise but also ELEVIDYS? Thank you.

The confirmatory trial for—okay. I guess you mean the ENVISION trial. Louise, I'll turn this to you.

Sure. The last patient last visit for ENVISION is in 2027.

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

Hey, good afternoon. Thanks for taking the questions. I guess just in regards to the changes at CBER and meetings with the FDA, you said that you're expecting a decision on labeling update to ELEVIDYS no later than the fourth quarter. I'm just wondering, is there any sort of formal meetings that are held with CBER along with that? Or is it just sort of an internal review until they make that decision? And then when we first heard about the patient death, I know there's a complicating factor with the reactivation of latent virus. So I was just wondering if the wound up being a biopsy, and if you had anything informative on that front.

I'll answer the last part of it to make it easier on Louise. We don't have the autopsy results yet. We're waiting for them. We should get them in the next month, or they may or may not be additionally informative. And as to the first of your questions, I'll turn this to Louise.

Regarding the label update, the FDA would just come back with any questions along the way if needed. Really, it's more of finalizing the label update, not necessarily that we're awaiting a decision on it. They've already confirmed that they are in general agreement. So it's really just going through the process now.

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

Good afternoon and thanks for taking the question. Maybe just another one on ELEVIDYS trends and more recently, just curious if there's been a shift in the age of the patients being treated or in the ambulatory status of those patients being treated? Thanks.

Yeah. Thanks for your question. I think it's too early to know precisely what the trend is. What I can tell you, which is a little more anecdotal than precise trending, is that we are continuing to see both ambulatory and nonambulatory start forms coming in. So I don't know if we track this out two months if that 40% will go down to 35%. But as it stands right now, we're seeing good uptake in both ambulatory and nonambulatory from a start form perspective. And I will say, let me forecast the future a bit; of course, the real issue is what happens when the information gets out to patients. One of the things I want to remind us about is that there is no difference in any of the markers, any of the elevated liver enzyme markers, any of the bilirubin marker; there is no difference between ambulatory and nonambulatory, and for instance, risk of elevated liver enzymes or liver injury. So there really should be no reason if we educate properly why there would be a significant difference in start forms.

Thank you. One moment for our next question. Our next question comes from the line of Gil Blum of Needham & Company. Your line is now open.

Good afternoon, and thanks for taking our question. Maybe a different approach for kind of the same topic as it relates to the patients who kind of took a minute to think about whether to go on treatment post the event. Was there any commonality across them, more ambulatory, nonambulatory, or is just the timing thing? Thank you.

So, I'm sorry, timing. It's just a timing thing. They were in March, and that was approximately in very end of February, early March was the announcement.

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

Thanks very much. We noticed the company recently hosted a meeting with PPMD after the patient death. I'm just wondering how impactful were these interactions? I know that there's an upcoming annual conference in June, so I'm wondering what are the company's plans now to interact with these organizations? And what do you think you need to emphasize with these families to underscore the positive risk-benefit of ELEVIDYS?

Yeah. I mean I think that webinar was very meaningful, but it's not the end. I think we are committed to giving the broad community—remember, there are some 10,000, 12,000, 13,000 Duchenne patients in the United States. We need to get the information out to the broad community so they can make intelligent decisions and evidence-based decisions with their physicians. At the same time, by the way, side now. We have to do the same thing with the physicians because they—the physician is the ultimate guider for the decisions of the families. The information that we have to get out to the world is both the safety profile of this therapy but also the efficacy profile of this therapy. We can't leave one behind because we can't make a good risk-benefit decision without it. And that's one of the things that we need to do. I think in part because of the amount of data we have and the fact that that data has come in over a significant period of time, I sometimes worry that people aren't seeing all of the information and all of the evidence of the benefits of ELEVIDYS together because it's a really impressive package that I think to any rational physician will indicate that this therapy is a significant disease modifier that has the potential for stopping this ferocious muscle damage or at least a significant amount of the muscle damage and then slowing or fully arresting the decline that is inevitable with Duchenne for anyone that doesn't get treatment. We just need to get that—we need to get all of that out. I think one of the things we focused on very significantly in that recent webinar, of course, was sharing the most recent information about the safety event. I think that was extraordinarily appropriate. On a go-forward basis, we need to talk about all of it in the context of all the safety and the efficacy available to us, and we are committed to doing that.

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

Great. Thanks for taking our questions. Great. First, I would like to ask for a clarification question regarding the uptick that you anticipate in the summertime for patient demand based on some leading indicators you're seeing. The question is, there must also be a leading indicator of some decline, and that's because you're lowering guidance. How do we reconcile a decline and also an uptick? Could we assume that you're seeing a pickup in the pace of the starting—patients' start forms coming in towards the more recent period? And then sorry about that long-winded question, a follow-up in a much straightforward question about peak sales estimate; do you have any comment on whether you are changing your guidance on the peak sales and the time to reach that peak? Thank you.

So on your first question, both are great questions; let me answer them. On your first question, the lowering of guidance is multifactorial, as I've mentioned, but there's no doubt that as a result of the safety events and the need to get more information out to patients, we saw a drop-off initially. Now when we say we're already seeing an uptick, and we're going to see a more significant uptick in the summer, that's because that's what we're seeing. So someone asked earlier, why are you assuming a flat to down second quarter? It's because this is a long cycle time therapy and a lot of people need more information to contextualize things and that costs as we're getting that information out. We're already seeing that uptick in start forms. When we talk to the families but also sites, it's quite clear that there is a belief among everyone that they’re going to see a very significant uptick in the summertime when you get past the school year and some of those issues. So I hope that answers your question. The second issue was on peak year sales. We’re not prepared yet to talk about peak year sales, but I want to put the concept of peak year sales in the context of a onetime therapy. Normally, the peak year sales is an indication of the ultimate opportunity of the therapy. Onetime therapies are different; it's an under—it’s essentially area under the curve analysis. So how long it takes to get to peak will change the actual peak, but the same opportunity exists essentially under the curve. There’s no reason to believe that the opportunity has become any less diminished now even though we are reducing our guidance for this year because of some of it being cycle time, some of it being some educational needs, some of it being some imbalances in sites that we need to address. The ultimate opportunity remains the same. We are correct in our epidemiology. We know the patient population and the size of it. There’s no reason to believe there’s any smaller population that is amenable to. The same opportunity exists. What that—what a delay in uptake implied by the $500 million delta in our guidance implies. What that means for peak year sales is something we’ll have to calculate and then look at it and talk later, maybe later this year, maybe early next year, something along those lines. But the opportunity remains the same. The same ultimate NPV should exist in either case.

Thank you. One moment for our next question. And our next question comes from the line of Kostas Biliouris of BMO Capital Markets. Your line is now open.

Hi, everyone. Thanks for taking our question. To the extent you can comment on that, can you talk a little bit about the decline of ELEVIDYS ex-US sales quarter-over-quarter? And to what extent those three headwinds you mentioned for the US may also apply ex-US, at least anecdotally? Thank you.

Well, I'm hesitant to discuss our partners' sales, and I would allow our partner to comment on it. I'd be surprised if it related to any of the cycle time issues or even the safety event or the like that we have in the United States, but I would have to beg off that question and ask you to ask Roche about that.

Thank you. One moment for our next question. And our next question comes from the line of Anupam Rama of JPMorgan. Your line is now open.

Sorry about that. Thank you so much for taking the question, guys. Just a quick clarification question. Louise, I think you said in April, you submitted a labeling update and had some of the patient—what you knew about the patient death information. But what else was included within that labeling update? Did it include the two-year EMBARK safety update? Did it include any real-world safety updates? What all was included in that?

Louise?

This is just updating the safety information. So this is about including the information around this particular case previously. It was just around ALI. So now this included ALF and the case. So that was the breadth of the uptake.

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

Yeah. Hi, guys. Thanks for taking my question. At the end of February, the company mentioned on its year-end call that there was ample site capacity for both infusion and follow-up. So I just want to kind of ask how site capacity changed over the last two months? Or what—or do you think it was more driven by patients being more cautious and need more handling before they sign up for administration? And I think on that last point, is there anything the company can do to provide risk mitigation strategies to physicians, given I think the community is looking for clarity that would de-risk future events?

Let me say a couple of things. One, we do, in aggregate, have good site capacity. The issue that we have, as I mentioned in my opening remarks, is a bit of an imbalance where if you just focus on the top sites, by the way, the top sites are responsible for about 60% of our current sales. They've been so sufficiently successful and enthusiastic along with their patients that they are often booked all the way out. Some are booked out by a year or more. So it's not simply about capacity because we can't—let's be clear. You can't redirect a start form that's sitting at site X that's got a one-year delay to site Y over in filling the blank, Indiana, it's just sitting there. So we've got to make all of the sites more productive, which is on us. We’ve got to get out and educate, work with them and the like. And so that's the issue. Do I think that there was some drop-off in March from families that you would say hand-holding in my view would be needed for more information and the like? Absolutely, I think that absolutely did happen. And I think we're doing the work there, and I think it works very well because the data and evidence is very supportive of the risk/benefit of this therapy. And then on risk mitigation, I would just say we have a wealth of risk mitigation in this very commendable safety profile therapy, may be very clear. Like, we proactively placed into the label a significant amount of monitoring, which physicians follow. We have these concepts called SAREPTA EXCHANGE, which is really one of a kind, where physicians in any site can get access to some of the world's leaders nearly on a real-time basis if they have questions or the like when they're infusing. I think the thing that's going to give people the greatest confidence is the data itself because the safety event that we saw earlier this year was a tragic one for that family, no doubt. But that is in the context of mediated gene therapy generally, and it has to be put in context of the number of patients that we've dosed. I mean, I would remind you we hear often of people that announced data one patient, or two patients, or three patients. We dosed well over 800 patients. So generally speaking, we know the safety profile of this therapy. If something comes out, there's going to be an autopsy that's going to—we're going to have access to in the next couple of months. If something comes out there that can provide additional insight, there were some signals, a signal of a CMV, which is unusual, a signal of another illness perhaps in December. If something comes out of that autopsy that's enlightening, we'll certainly bring it to the community. I think though, the experts, which I am not on a not yet confident that there'll be something out of the autopsy that will provide additional insight. I think the greatest insight that families can have to make risk-based decisions is just to understand this therapy, what it can do for these families, how it can protect muscle. On the other side, what a generally commendable safety profile it has in the context of a serious AAV-mediated gene therapy.

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

Hi, guys. Thanks for taking the questions. So I just wanted to ask one on any anecdotal experience broadly for patients that have been dosed to date with commercial ELEVIDYS, what you hear from the docs and families matches up with what you know from EMBARK in the clinical trial experience? And then just with the PMOs, how should we think about cannibalization of the products, given how the ELEVIDYS commercial uptake curve may be changing? Thanks a lot.

Yeah. On the first one, you referenced it as anecdotal. So take that with a grain of salt. It's anecdotal; unfortunately, we don't get approvals on anecdote; we get approval on evidence. The anecdotes amaze very clear. I mean one of the things that during this very difficult and chaotic time that exists in the broader market in biotech specifically and certainly at Sarepta specifically, it is comfort to me when I get videos from families. We're seeing a lot of extraordinary stories from families, kids that are riding bikes, kids are running up and down at an age when they ought to be in a powered wheelchair, kids outpacing their father who's trying to catch them in the woods. There's one particular individual video I watch often. So what that doesn’t mean much; it’s only anecdote, but we get a lot of great anecdote. I think when families begin to get the opportunity to talk to other families and see the experience they're having, not only the experience of getting—going through the process to get infused in the infusion process and the like, but then seeing what it may mean to them and their life going forward. I think it's going to be very, very motivating for families who as yet may not have a start form.

Thank you. One moment for our next question.

One other thing I should say, I think there’s some interesting information on that in our website, I believe, yeah.