Q1 2025 Sarepta Therapeutics Inc Earnings Call

[music].

Mary Jenkins: Good afternoon, and welcome to the Sarepta Therapeutics first quarter 2025 financial results conference call. As a reminder, today's program is being recorded.

Good afternoon, and welcome to the cigarette that therapeutics first quarter 2025 financial results Conference call.

As a reminder, today's program is being recorded at.

Mary Jenkins: At this time, I'll turn the call over to Mary Jenkins, Associate Director, Vesta Relations. Please go ahead. Thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2025.

Speaker Change: At this time I will turn the call over to Mary Jenkins Associate Director Investor Relations. Please go ahead.

Speaker Change: Thank you Marvin and thank you all for joining today's call.

Speaker Change: Earlier. This afternoon, we released our financial results for the first quarter of 2025 of the press release and supplementary information are available on the investors section of our website at threat Dot Com and our 10-Q was filed with the SEC. This afternoon, joining us on the call today are Doug Ingram, E&S, Japan down Murray and Dr believes Regina playback.

Mary Jenkins: 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.

Mary Jenkins: Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise Rodino-Clapak.

Mary Jenkins: After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we were 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.

After our formal remarks, we'll open the call for Q&A.

Speaker Change: I'd like to note that during this call we were making a number of forward looking statements. Please refer to slide two on the webcast, which contains our forward looking statements. These forward looking statements involve risks and uncertainties many of which are beyond throughout this control actual results could materially differ from these forward looking statements and any such risks can materially and adversely affect the business.

Speaker Change: The results of operations and trading prices for scrap this 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.

Mary Jenkins: 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.

Mary Jenkins: 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 investor section of our website.

Speaker Change: As noted on slide three 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 will turn the call over to our President and CEO, Doug Ingram, who will provide an overview of.

Doug Ingram: 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.

Doug Ingram: Our recent progress Doug.

Speaker Change: Mary.

Doug Ingram: 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 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 and significant revenue, a strong P&L and 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.

Speaker Change: Afternoon, everyone and thank you for joining us corrupted therapeutics first quarter 2025 financial results Conference call.

Speaker Change: Across biotech and indeed, the market more generally the first quarter of 2025 has been a challenging one for.

Speaker Change: Likewise for <unk>, we have faced challenges that have motivated us to take a more measured view for the remainder of 2025, Fortunately threat to us in a better position than most of biotech today as we are a significant number of approved therapies and significant revenue a strong P&L and balance sheet and the ability to continue to independently drive our port.

Speaker Change: Folio of gene therapies, and <unk> programs, we are well positioned to weather this chaotic period.

Doug Ingram: 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 Elevit has achieved sales of $375 million in the quarter, representing a 180% increase over the same quarter last year. While our elevitous first quarter growth still represents the most successful in vivo gene therapy launch yet in history, in fact, in Q1, we treated more patients with gene therapy than ever before in the U.S. in a single quarter, we nevertheless fell short of expectations.

Speaker Change: In the first quarter of 2025, we achieved $612 million in total net product revenue, representing 70% growth over the same quarter last year.

Speaker Change: Our PMO franchise grew 5% achieving $237 million for the quarter and.

Speaker Change: <unk> achieved sales of $375 million in the quarter, representing a 180% increase over the same quarter last year.

Speaker Change: While our 11 as first quarter growth still represents the most successful in.

Gallon: In vivo gene therapy launched yet in history in fact in Q1, we treated more patients with gene therapy than ever before in the U S. In a single quarter. We Nevertheless fell short of expectations in a moment gallon will explain some of those quarterly factors, including administrative issues a severe flu season resulted in delays in there.

Doug Ingram: In a moment, Dallan will explain some of those quarterly factors. Administrative Issues, Severe Flu Season that resulted in delays in the effect of the recently reported safety event that motivated some families with scheduled infusions to pause for additional information.

Gallon: Effect of the recently reported safety event that motivated some families with scheduled infusions to pause for additional information.

Doug Ingram: Looking forward, we are changing our Net Product Revenue Guidance for the year. $2.3 billion to $2.6 billion across our four approved therapies. This change is driven by three factors.

Gallon: <unk> forward, we are changing our net product revenue guidance for the year.

Gallon: The $2 3 billion to $2 $6 billion across our four approved therapies that change is driven by three factors.

Doug Ingram: First, as you know, we recently reported that a boy infused with a Levitas suffered an acute liver failure and passed away. This was an unimaginably tragic event for that family, who with a levitist finally had reason to hope for a brighter future for their son. At Sarepta, we are deeply committed to the patients we serve. So this event, so markedly different than all other experience with elevators. was heartbreaking for all of us. Well, it is of no comfort to the family involved. It's important to remember that more than 800 patients have been infused with a Levitas.

Gallon: First as you know, we recently reported that a boy infused with a limited suffered an acute liver failure and passed away.

Gallon: This was an unimaginable tragic event for that family, who with Leavitt has finally had reason to hope for a brighter future for their son.

Gallon: At <unk>, we are deeply committed to the patients we serve so this event so markedly different than all other experience with <unk> with.

Gallon: It was heartbreaking for all of us.

Gallon: Well it is of no comfort to the family involved it's important to remember that more than 800 patients have been infused with <unk>. The outcome of this event is inconsistent with all other experience with <unk> and we are continuing to explore what was uniquely different about this case.

Doug Ingram: The outcome of this event is inconsistent with all other experience with a Levitas, and we are continuing to explore what was uniquely different about this case than every of the other hundreds and 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 Levitas more specifically, nor did it change the positive risk benefit of Levitas, which has had a stable and laudable safety profile in the context of AAV-mediated gene therapy since first being infused back in January of 2018.

Gallon: Then every of the other hundreds and hundreds of infusions that have occurred to date, but we do know is that while this young man's outcome with surprise.

Gallon: This did not represent a new safety signal for AAV mediated gene therapy, generally or <unk> more specifically nor did it change the positive risk benefit of <unk>, which has had a stable and laudable safety profile in the context of AAV mediated gene therapy since first being infused back in January of <unk>.

Gallon: 2018.

Doug Ingram: And 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 or executed program, one called Sarepta Exchange, that provides physicians with near-real-time access to the most experienced and leading experts around the world so that outcomes are consistent across the country. We also provide education for our patient community, and we 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 Alevitus.

Gallon: And of course to support our optimal outcomes, we have always prioritized patient safety. We are 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 are executed program one called <unk> to exchange that provides.

Gallon: <unk> positions with near real time access to the most experience in leading experts.

Gallon: Around the world So that outcomes are consistent across the country. We also provide education for our patient community and we are committed to providing timely information about this life enhancing therapy.

Gallon: 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 <unk>, but there will be an impact on infusions as we rollout education in the broader physician community and families gain better insight into the profile.

Doug Ingram: But there will be an impact on infusions as we roll out education and the broader physician community and families gain better insight into the profile of this disease-modifying therapy and have their questions answered.

Gallon: All of this disease modifying therapy and have their questions answered.

Doug Ingram: 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 have 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 you know, we are quite proficient in working with sites to gain access.

Gallon: Second.

Gallon: 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've launched the broader label and expanded the actual cadence from start form.

Gallon: Two 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 you know we're quite proficient in working with sites to gain access in fact for our PMO our ultimate.

Doug Ingram: In fact, for our PMOs, our ultimate rate for gaining payer access has been well over 90%. And for Elevitus, 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. But 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.

Gallon: Right for gaining payer access has been well over 90%.

Gallon: And for <unk>. It currently remains at 100%.

Gallon: 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, but for purposes of setting guidance for the year, we are assuming our first quarter <unk>.

Gallon: <unk> turnaround times as 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.

Doug Ingram: Finally, three, the success we have seen with Top Sites has caused an imbalance that we need to address across this year. 60% of our current revenue comes from Top Sites and Top Thought Leaders. Their experience and enthusiasm for Levitas has 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.

Gallon: Finally, three the success, we've seen with top sites has caused it and balance that we need to address across this year, 60% of our current revenue comes from top sites in top thought leaders their experience and enthusiasm for <unk> as a resulted in many of them being fully booked out to 12 months, we need to direct much.

Gallon: Our attention going forward to sites with more capacity.

Doug Ingram: We do not take lightly our decision to change guidance, but given the environment and some of the constraints we are working to address, we do believe it prudent. What we do know is this, Elevitus 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 restorer of significant amounts of a form of muscle-protecting dystrophin, and as observed over multiple studies, over eight years of clinical experience and clinical evidence and in hundreds of patients of data, it is the only gene therapy proven to preserve function in boys dying from Duchenne.

Gallon: We do not take lightly our decision to change guidance, but given the environment and some of the constraints. We are working to address we do believe it prudent.

Gallon: But we do know is this <unk> is the first and only available disease modifying therapy that offers the possibility of arrest arresting further muscle damage in 80% or more of patients being daily damaged by Duchenne muscular dystrophy. It.

Gallon: It is a disease modifying restore a significant amounts of a form of muscle protecting dystrophin and as observed over multiple studies.

Gallon: Eight years of clinical experience in clinical evidence and in hundreds of patients of data. It is the only gene therapy proven to preserve function in boys dying from Duchenne without intervention everyday muscle of boys with Duchenne is destroyed and permanently replaced by fat and fibrotic tissue.

Doug Ingram: Without intervention, every day, 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 a Levitas 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.

Gallon: With the FTA following the positive expert advisory panels, and approving <unk> broadly for boys with Duchenne.

Gallon: Families. Finally, now have a chance to choose a different journey.

Gallon: Now that a disease modifying therapy is finally available to them. The families are delayed in getting a therapy that can finally protect them from duchenne relentless damage and they are delayed either because of administrative issues or other delays or lack of information or even at times.

Doug Ingram: 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 or other delays or lack of information or even, at times, circulating misinformation, then we will have failed in our mission and I hope we have proven repeatedly over these last eight years that we do not intend to fail in our mission.

Gallon: Circulating misinformation.

Gallon: And we will have failed in our mission and I hope we have proven repeatedly over these last eight years and we do not intend to fail and our mission.

Doug Ingram: 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-Claypath. She will speak to you about the continuing evolution of data for the impressive efficacy of Elevitus and our plans to expand even further the population of patients who will have access to Elevitus.

Gallon: After our chief customer Officer, Dallas Murray provides an overview, we will hear from our head of R&D and Chief Scientific officer, Dr. Louise Rodino quite back.

Gallon: She will speak to you about the continuing evolution of data for the impressive efficacy of <unk> and our plans to expand even further the population of patients who will have access to <unk>.

Doug Ingram: Finally, Dr. Rodino-Clayback will provide an overview of the great progress we are making on our LGMD portfolio and will discuss our progress with our SIRNA platform, including our plans to share our proof of biology and proof of concept data from both our FSHD and DM1 programs The second half of this year.

Gallon: Finally, Dr. Rodino playback will provide an overview of the great progress we are making on our <unk> portfolio and we will discuss our progress with our RNA platform, including our plans to share our proof of biology and proof of concept data from both our Fsh D and DM one programs.

Gallon: In the second half of this year.

Dallan Murray: And with that, let me turn the call over to our Chief Customer Officer, Dallan Murray. Thank you, Doug, and good afternoon. My comments today are focused on three areas.

Speaker Change: And with that let me turn the call over to our Chief customer Officer Dallin Mary Ellen.

Speaker Change: Thank you Doug and good afternoon. My comments today are focused on three areas context for what happened in Q1.

Dallan Murray: 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.

Speaker Change: We plan to achieve our revised full year guidance for 2025.

Speaker Change: And what gives us confidence in our ability to achieve that guidance.

Speaker Change: Regarding our Q1 performance. In addition to the safety event there were two issues that impacted our results late into the quarter.

Speaker Change: 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 medical California's Medicaid program that pushed out patients infusion dates.

Speaker Change: Fortunately these specific administrative challenges have now been successfully resolved.

Dallan Murray: Now I'll outline how our first quarter performance informed 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 out more information. We immediately initiated extensive outreach to our leading traders 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 EMBARQ 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.

Speaker Change: Now I will outline how our first quarter performance informed our revised guidance and the actions we will take it.

Speaker Change: First the safety event led some patients and families scheduled for late March dosing to delayed treatment, while they sought out more information.

Speaker Change: We immediately initiated extensive outreach to our leading treaters and the broader community conversations have revealed that access to comprehensive safety data, including our biomass marker safety data, which Luis will discuss in her prepared remarks.

In conjunction with the two year embarked data provides the necessary context for health care providers and patients to move forward with confidence.

Speaker Change: Our current focus is on disseminating this information across the wider treating and referring physician landscape, which is a process that takes time.

Dallan Murray: 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.

Speaker Change: As a result, we anticipate Q2 revenue could be as much as 20% lower than Q1.

Speaker Change: 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.

Speaker Change: Furthermore, we are encouraged that we continue to receive enrollment forms for both ambulatory and non ambulant patients.

Dallan Murray: 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 therapy. However, with the broader label and our expansion to a wider range of patients, the actual start form to infusion cadence is extending by one to one and a half months beyond initial aspiration. 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.

Secondly, as we discussed the administrative paths for gene therapy from initial paperwork to infusion is inherently complex involving significantly more appointments tests and steps the typical therapies.

Speaker Change: However, with the broader label and our expansion to a wider range of patients. The actual start form to infusion cadence is extending by one to one five months beyond initial estimates.

Speaker Change: This longer duration is primarily attributable to more rigorous screening protocols implemented implemented to ensure patient safety within this expanded population coupled with the intricate logistical requirements at the site level.

Speaker Change: Including the navigation of single case agreements with payers.

Dallan Murray: 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 guide.

Speaker Change: 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.

Speaker Change: But while we are working to shorten turnaround times, we are nonetheless, taking a conservative approach.

Speaker Change: Incorporating the longer Q1 turnaround in to our revised 2025 guidance.

Dallan Murray: Thirdly, regarding site capacity. We observe 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.

Speaker Change: Thirdly regarding site capacity.

Speaker Change: We observe a dichotomy across our network.

Speaker Change: Our total network capacity is robust our most established and recognized treatment sites are facing substantial demand, resulting an appointment the times approaching a year due to near full operational capacity.

Speaker Change: 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.

Speaker Change: Our strategy involves a proactive approach to engage these centers.

Speaker Change: More deeply through enhanced high touch support like we've done with the leading treatment centers.

Speaker Change: 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.

Dallan Murray: Lastly, our teams are now intensifying their efforts to promote the deep and impressive evidence for the benefits of Elevitus. We launched our comprehensive HCP and patient promotional campaign in the first quarter, which includes a fully built out Elevitus.com website and significant direct-to-consumer investment through digital channels designed to drive awareness and understanding.

Speaker Change: Lastly, our teams are now intensifying their efforts to promote the deep and impressive evidence for the benefits of <unk>, we launched our comprehensive HCP and patient promotional campaign in the first quarter, which includes a fully built out to <unk> dot com website and significant direct to consumer investments through digital.

Speaker Change: Channels designed to drive awareness and understanding.

Dallan Murray: With focused work already underway to address these three key areas, education, tightening turnaround times, and site to pass the optimization, we have a clear path forward to effectively support the patient community and achieve our revised guidelines. 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.

Speaker Change: This focused work already underway to address these three key areas education tightening turnaround times and site capacity optimization.

Speaker Change: We have a clear path forward to effectively support the patient community and achieve our revised guidance.

Speaker Change: 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.

Dallan Murray: Thank you for your attention today.

Louise Rodino: 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 <unk> APAC Louise.

Louise Rodino: And with that, I would like to hand over the call to our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Kleipak. 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.

Louise Rodino: Thank you Alan.

Louise Rodino: They're all of science and transforming patient lives has never been more important than it is at this moment.

Louise Rodino: Throughout the science is foundational to who we are.

Louise Rodino: I'll focus my comments today in three areas. Levitas, including additional data that support safety and efficacy, the progress we've made in advancing our limb girdle portfolio, solidifying our scientific leadership in neuromuscular disease. and the momentum behind our siRNA therapies, including the opportunity they hold to be best in class.

Louise Rodino: I'll focus my comments today in three areas.

Louise Rodino: All evidence, including additional data that supports the safety and efficacy.

Louise Rodino: The progress we've made in advancing our limb girdle portfolio solidifying our scientific leadership in neuromuscular diseases.

Louise Rodino: And the momentum behind our <unk> therapy, including the opportunity they hold to be best in class.

Louise Rodino: 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 non-existent or inadequate.

Louise Rodino: Further we are excited to share the depth of our research at our upcoming R&D day later this year.

Speaker Change: Michael Hill, future innovation to treat diseases for which therapies, either non existent or inadequate.

Louise Rodino: Beginning with Elevitas. We've provided data to the FDA and will continue to work with them on any necessary updates to the elevative 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 a Levitas, we see no difference in the rates of adverse events in relationship 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.

Louise Rodino: Beginning with a loving it.

Louise Rodino: Provided data to the FDA and we will continue to work with them on any necessary updates to the collaborative playable are monitoring requirement.

Louise Rodino: 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 important and timely manner and that we addressed my question.

Louise Rodino: Regarding safety in patients treated with <unk>.

We see no difference in the rates of adverse events and relationship to age or weight.

Louise Rodino: Furthermore, no relationship with that identified between a liver safety Biomarkers bilirubin, GGP and INR and the total dose administered or patient age or patiently.

Louise Rodino: Shown on this slide are Billy Rubin values versus all cohorts in Study 103 and EMBARQ. 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 supports safety of elevatives weight-based dosing across the labeled population of patients with Duchenne, regardless of ambulatory status.

Louise Rodino: Shown on this slide our bilirubin value versus all cohorts and studying 103 and embark.

Louise Rodino: Regardless of whether it's changed from baseline absolute peak or peak value.

Louise Rodino: No correlation with weight or age.

Louise Rodino: The same holds true for cardiac safety biomarkers, including Japan.

Louise Rodino: The totality of our data and over 800 patients support safety of <unk>.

Louise Rodino: Everything across the labeled population of patients with Duchenne.

Louise Rodino: Our list of ambulatory data.

Louise Rodino: Life Cycle Development for Elevitus continues to progress, highlighted by multiple activities. Starting with Envision, our post-marketing commitment trial for Elevative. envisions a phase 3 global placebo-controlled trial in older ambulatory and non-ambulatory individuals with Duchenne and has progressed well. In the United States, enrollment is complete and we continue to dose XUS. Our last patient, last visit is expected in 2027, following an 18 month placebo control period.

Louise Rodino: Lifecycle development for all of it is continues to progress highlighted by multiple activity.

Louise Rodino: Starting with envision our post marketing commitment trials are loving it.

Louise Rodino: <unk>, a phase III global placebo controlled trial in older ambulatory and non ambulatory individuals with Duchenne and has progressed well.

Louise Rodino: In the United States enrollment is complete and we continue to dose escalate.

Louise Rodino: Our last patient last visit is expected in 2027, following an 18 month placebo controlled period.

Louise Rodino: Next for AAV Rh74 antibody positive. We are conducting two studies, study 104 with embolicidase to cleave antibodies and study 105 to remove antibodies with plasma-free. 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 elevators and publish and share these scientific data in support of the DMD population. The evidence continues to build, supporting safety and efficacy of elevators, particularly as time progresses as compared to the national history.

Louise Rodino: Next for AAV are 74 antibody positive patients. We are conducting two studies study one off well with them listening to cleave antibodies in study 105 to remove antibodies with plasma free.

Louise Rodino: 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 all evidence and published and share the scientific data in support of the DMD population.

Louise Rodino: Evidence continues to build putting safety and efficacy of <unk>, particularly as time progressed as compared to the natural history.

Louise Rodino: In that spirit, we shared important updates at this year's MDA meeting, including results from our two-year EMBARQ and three-year pooled analyses 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, EMBARQ Part 1 elevitist-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, and as previously mentioned on last quarter's call, the muscle MRI data we observed showed minimal progression in underlying muscle pathology in a Levitas-treated patient.

Louise Rodino: Spirit, we shared important updates at this year's NDA meeting.

Louise Rodino: <unk> results are our two year embark and three year pulled analysis, indicating stabilization or slowing of disease progression compared with well matched external control.

Louise Rodino: By functional outcomes.

Victor for delaying loss of ambulation.

Louise Rodino: At two years embark part 111 has treated patients demonstrated statistically significant and clinically meaningful functional benefit in NSA, a total score time to rise and 10 meter walk run versus the propensity score weighted external control cohort.

Louise Rodino: In addition, and as previously mentioned on last quarters call. The muscle MRI data, we observed some minimal progression and underlying muscle pathology and a lot of it is treated patient.

Louise Rodino: underscoring the importance of treating as soon as possible to preserve muscle.

Louise Rodino: Underscoring the importance of trading as soon as possible to preserve muscle.

Louise Rodino: Lastly, we're looking forward to sharing additional data from the EMBARQ study at this year's ASGCT's annual meeting this month in New Orleans, Louisiana.

Louise Rodino: Lastly, we're looking forward to sharing additional data from the embark study at this year's <unk> annual meeting this month in New Orleans, Louisiana.

Louise Rodino: Moving now to our programs for the Lungardal Muscular Dystrophy or LGMD. Each of the LGMD programs builds on our experience with Elevitis. We use the same vector, RH-74, in both Elevitis and our LGMD program, which has a differentiated safety profile and high transduction efficiency.

Louise Rodino: Moving now to our programs to the limb girdle muscular dystrophy or <unk>.

Louise Rodino: Each of the algae MD program builds on our experience with a lot of it we use the same vector or a 74 and Basel evidenced in our <unk> programs, which has a differentiated safety profile and high transduction efficiency.

Louise Rodino: To this end, we've requested a platform technologies designation to enable leveraging of shared technology in future applications. We were thrilled to announce in December 2024 that we completed enrollment and dosing of study SRP9003-301, or emergine, or phase 3 clinical trials, SRP9003, to treat LGMD type 2 E or beta-cycloglycanopathy. Emerging as a global study and the primary endpoint is biomarker expression of the beta-circle glycan protein. A pre-VLA 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 Elevitus and SRP 9003, we have agreement to leverage Elevitus data in the SRP 9003 DLA.

Louise Rodino: To this end we've requested a platform technology designation to enable levered leveraging of shared technology and future applications.

Louise Rodino: We are thrilled to announce in December 2024 that we completed enrollment and dosing study SRP 9003 301 are encouraging.

Louise Rodino: Phase III clinical trials, SRP 9003 to treat L. J M D type two E or beta size look like apathy.

Louise Rodino: Emerging as a global study the primary endpoint is biomarker expression of the beta circled black and protein.

Louise Rodino: Prevail a meeting has occurred and the office of therapeutic products C. P is confirmed eligibility for the accelerated approval pathway for this program.

Louise Rodino: Due to the similarities between <unk> and FRP, neither us or all three we have agreement to leverage 11 of data and the SRP 903 delay.

Louise Rodino: Director remains on track to submit a BLA to the FDA in the second half of 2025.

Louise Rodino: Chapter remains on track to submit a BLA to the FDA in the second half of 2025.

Louise Rodino: We are also encouraged by the progress of our other LGMD programs. Just last month, we announced that we completed enrollment and dosing and study FRP 9004-102 or a discovery study. Discovery is a Phase I proof-of-concept study evaluating safety and expression of the alpha-cycloglycan protein after treatment with SRP9004. SRP9004 is in development to treat LGMD Type 2D, or Alpha-Circle Glycanopathy. We plan to initiate our Phase 3 trial before the end of the year.

Louise Rodino: We're also encouraged by the progress of our other <unk> programs just last month, we announced that we completed enrollment and dosing study SRP 900410 to our discovery study desk.

Louise Rodino: Discoveries are phase one proof of concept study evaluating safety and expression of the alpha cycle glycoprotein after treatment with SRP 9004.

Louise Rodino: <unk> four is in development to treat L. J M. D type can be also cyclical economically.

Louise Rodino: Plans to initiate a phase III trial before the end of the year.

Louise Rodino: Also last month, we announced the following input from OTP. We were clear to proceed with study SRP 9005-101 for our COMPAS study in the United States. Compass is a first-in-human clinical study of SRP 9005, which is in the development for the treatment of LGMD type 2C, or gamma-circoglycanopathy. As a reminder, and 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 DLA.

Louise Rodino: Also last month, we announced that following input from Otp. We were cleared to proceed with study FRP 9005, 101, or a combo study in the United States.

Louise Rodino: <unk> is a first in human clinical study of SRP 9005, which is in development for the treatment of <unk> to see our gamma cycles like in op IV.

Louise Rodino: As a reminder, and with support from the agency, we adopted a phase <unk> seamless design clinical trial for SRP 9005, with the aim of facilitating a more efficient and faster path to BLA.

Louise Rodino: 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 indication. Many of these programs are nearing its end. On the research side, we've continued to innovate across platforms, developing new AAV capsules, as well as driving innovation in gene editing and enhanced delivery for RNA. The momentum around our other programs continues, and we look forward to sharing data with you later this year around our FSHD-1 and DM-1 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, and broadening our focus into chronic therapies alongside one-time therapies.

Louise Rodino: We also look forward to highlighting our impressive pipeline and research at an upcoming R&D day in the latter half of 2025.

We have numerous programs in various stages of development across neuro muscular central nervous system cardiac and pulmonary indications.

Louise Rodino: Many of these programs are nearing indeed.

Louise Rodino: On the research side, we've continued to innovate across platforms, developing new AAV capsid as well as driving innovation in gene editing and enhance delivery for RNA.

Louise Rodino: The momentum around our other programs continues and we look forward to sharing data with you later this year around our Fsh D. One and <unk> one programs.

Louise Rodino: Beyond the multiple high value catalysts to come this year and into the coming years Rsi RNA program leverage dropped his successful track record in developing and commercializing neuromuscular therapies.

Louise Rodino: While also expanding our portfolio into CNS and pulmonary and broadening our focus into chronic therapies alongside onetime therapy.

Louise Rodino: SRP 91001 is currently in clinical development.

Louise Rodino: SRP1001 is currently in clinical development to treat FSHC1 and we are encouraged by the non-clinical data generated thus far. Cohort 2 in the FAD study is now fully enrolled, and we look forward to the data readout later this year.

Louise Rodino: Q1, and we are encouraged by the non clinical data generated thus far.

Louise Rodino: Cohort two in the Sad study is now fully enrolled and we look forward to the data readout later this year.

Louise Rodino: 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.

Louise Rodino: Turning to Myoclonic dystrophy type, one or Dan one cohort one in the Sad study is now fully enrolled and we look forward to sharing the data from that study later in the year.

Louise Rodino: Now to discuss our PMO plan. The Essence Trial, our post-marketing requirements for Goladarsan and Casimirsa, as well as Mission, a post-marketing commitment for Exondus, 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 RPMO.

Louise Rodino: Now to discuss our PMO platform.

Louise Rodino: Essence trial or post marketing requirement for Cologuard and customers as well as mission a post marketing commitment for example.

Louise Rodino: Fully enrolled and remain on track.

Louise Rodino: We look forward to sharing data soon as these studies are completed and continued to collect and publish real world data on the long term effects of our PMO.

Louise Rodino: 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 grab the opportunities before us because patients are waiting.

Louise Rodino: In closing I'd like to take this opportunity to thank my staff to colleagues and those on the patient and clinical community.

Louise Rodino: For those of us in the field of genetic medicine work continues and good science will always prevail well, let's grab the opportunity before us because patients are waiting.

Ian Estepan: I'll now turn the call over to Ian for an update on the financials. Thanks, Louise, and good afternoon, everyone. This afternoon's financial results press release provided details for the first quarter of 2025 on a gap basis as well as a non-gap 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.

Ian: I'll now turn the call over to Ian for an update on the financials.

Ian: Thanks, Luis and good afternoon, everyone.

Ian: 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.

Ian: Please refer to our press release available on <unk> website for a full reconciliation of GAAP to non-GAAP financial results.

Ian: Beginning in the first quarter of 2025, the gains and losses on Mark to market, our strategic investments are excluded from our non-GAAP results.

Ian: For comparison purposes, non-GAAP financial results for the first quarter of 2024 have been updated to reflect this change.

Ian Estepan: In Q1, we delivered strong year-over-year growth and revenue. Continued disciplined approach to investment in R&D and SG&A, and maintain our strong cash position with $647 million in cash, cash equivalents and investments, and restricted cash at 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 gap and non-gap operating loss of $300 million and $250 million, respectively, both included a $584 million R&D expense Associated with our Global Licensing and Collaboration and Stockpurs.

Ian: In Q1, we delivered strong year over year growth in revenue.

Ian: Continued disciplined approach to investment in R&D, and SG&A and maintained our strong cash position with $647 million in cash cash equivalents investments and restricted cash as of the end of the quarter and $600 million of additional liquidity available through our revolver.

Ian: The decrease in our cash balance from last quarter due to the funding of Arrowhead collaboration upfront consideration of $825 million with cash on hand.

Ian: We 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.

Ian: Associated with our global licensing and collaboration and stock personally stock purchase agreement with Arrowhead excluding.

Ian Estepan: Stock Purchase Agreement with Arrowhead. Excluding this transaction, we were reported a gap and non-gap 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%. Elevated net product revenue was $375 million and grew 180% year over year. And net product revenue from our PMO Exxon 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 on certain programs, as well as $17 million of contract manufacturing revenues for sales of commercial levitates supplied to Roche.

Ian: Excluding this transaction, we were reported a GAAP and non-GAAP operating profit of $283 million and $334 million respectively.

Ian: In the first quarter, we delivered $612 million and total net product revenue representing year over year growth of 70%.

Ian: <unk> net product revenue was $375 million and grew 180% year over year and net product revenue from our PMO exon skipping franchise with $237 million up 5% over the prior year.

Ian: In Q1, we recognized $133 million of collaboration and other revenues.

Ian: This primarily reflects a $112 million of collaboration revenues related to <unk> expired option on certain program as well as $17 million of contract manufacturing revenues for sale of the commercial that would supply to Roche.

Ian Estepan: The reimbursable co-development costs under the Roche Agreement, which is recorded as a contra-operating expense, total $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 increase in elevative sales as well as an increase in cost of sales related to products sold to Roche.

Ian: The Reimbursable co development costs under the Roche agreement, which is recorded as a contra operating expense totaled $29 million in Q1 compared to $22 million for the same prior year period.

Ian: Total revenues were $745 million in the first quarter and increased $331 million or 80% year over year.

Ian: Q1 cost of sales totaled $138 million compared to $51 million in the same period of 24.

Ian: Increase was driven by increased <unk> sales as well as an increase in cost of sales related to products sold to Roche.

Ian Estepan: Now moving to our R&D expenses. On a gap 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.

Ian: 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.

Ian: The increase was primarily due to the $584 million upfront and milestone expenses associated with Afro mentioned Arrowhead collaboration.

Ian: 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.

Ian: Now turning to SG&A on a GAAP basis, SG&A totaled $134 million up 5% year over year.

Ian Estepan: This increase was primarily driven by an increase in compensation and other personal expenses, and higher sales and marketing spending to commercialize the levitas. On a non-GAAP basis, SG&A expenses totaled $107 million, up 7% year over year. On a gap basis, we recorded an $83 million Millions Out of Charge and Other Expense Net Q125. This was primarily. Due to the loss on strategic investments, which includes a 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 the levinous revenue.

Ian: This increase was primarily driven by an increase in compensation and other personal expenses.

Ian: Higher sales and marketing spending to commercialize <unk>.

Ian: On a non-GAAP basis, SG&A expenses totaled $107 million up 7% year over year.

Ian: On a GAAP basis, we recorded an $83 million.

Ian: Million dollar charge in other expense net Q1 'twenty five this was primarily.

Ian: Due to the loss on strategic investments, which includes our recurring fair value adjustments of investments of publicly traded companies, including Arrowhead.

Ian: GAAP income taxes were $64 million in the quarter compared to $5 million in the prior year.

Ian: The increase is driven primarily by increased taxable profit largely due to the 11 as revenues.

Ian Estepan: Also on a gap 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-gap net loss of $332 million, or $3.42 per diluted share.

Ian: 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.

Ian: We reported non-GAAP net loss of $332 million or $3.42 per diluted share.

Ian Estepan: Now turning to our outlook for 2025, as mentioned earlier, we are revising our total product revenue guidance to $2.3 to $2.6 billion. This still represents a 37% increase from our 2024 total product revenue at the mid FEMA.gov 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, remains at $1.2 to $1.3 billion. However, we anticipate to be at the closer to the low end of the range. With our undrawn $600 million of evolving credit facility, we are in a strong position to further invest in internal and external innovation and to support our capital allocation strategy.

Ian: Now turning to our outlook for 2025 as mentioned earlier, we are revising our total product revenue guidance to $2 three to $2 $6 billion. This still represents a 37% increase from our 2020 for a total product revenue at the midpoint.

Ian: PMO guidance remains the same at around $900 million.

Ian: Our combined 2025, non-GAAP R&D and SG&A expenses, excluding the impact of the Arrowhead collaboration upfront transaction expense and potential <unk> development milestone remains at one two to $1 $3 billion. However, we anticipate to be at the closer to the low end of the range.

Ian: 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.

Ian Estepan: 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.

Ian: 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.

Doug Ingram: 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 Ingram: And with that, I'll turn the call over to Doug to start the Q&A. Doug? Thank you very much, Ian.

Doug Ingram: Thank you very much Ian Marvin lets open the lines for Q&A.

Unknown Executive: Marvin, let's open the lines for Q&A. Thank you. At this time, we'll conduct the question and answer session. To ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please limit yourself to one question.

Thank you at this time, we will conduct a question and answer session to ask a question you will need to press star one on your telephone and withdrew named to be announce to withdraw. Your question. Please press star one again please.

Doug Ingram: Please limit yourself to one question. Please standby, while we compile the Q&A roster.

Unknown Executive: Please stand by while we compile the Q&A roster.

Tazeen Ahmad: Our first question comes from a line of Tazeen Ahmad of Bank of America Securities. Your line is now open. Hi guys. So Doug, I just wanted to ask you, on those three... This one, as any, has been the biggest driver of potential downside pressure. And then, as 2Q has progressed, have any of those, I guess, gotten... Transcript by Transcription Outsourcing, LLC.

Speaker Change: Our first question comes from the line of Casino Man of Banc of America Securities. Your line is now open.

Speaker Change: Hi, guys. Good afternoon. 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 issue is the administrative processes that you mentioned and as a result of the patients leading families to have questions.

Speaker Change: Which one is any has been the biggest driver of potential downside pressure.

Speaker Change: You to revise guidance.

Speaker Change: And then.

Speaker Change: <unk> has progressed have any of the I guess gotten worse, because youre talking about 20% lower sales relative to <unk> and we're still pretty I guess relatively early into the quarter.

Doug Ingram: Thank you for your questions. So first on the balance, you know, it is a mix of all three. I think the cycle times Tazeen Ahmad, Biren Amin, Tim Lugo, Ritu Baral, Brian Abrahams, Uy Ear, Salveen Richter, Gil Blum, Gena Wang, Anupam Rama, Kristen Kluska, Ian Estepan, Douglas Ingram, Michael Ulz, Tyler Buren, Dallan Murray, Mike Ulz, Danielle Bongero, Tommie Reerink, Brian Skorney, Gavin Clark, Ry Forseth, Robert Finke, Priyanka Grover, Lin Tsai, Konstantinos Biliouris, Sarepta Therapeutics Inc What we're seeing going forward is not a worsening. In fact, again, we don't have enough data on the cycle time issue to suggest that we're being overly conservative, but we're at a minimum confident that we've hit steady state.

Speaker Change: Yes. Thank you for your question. So first on the balance it is a mix of all three I think the cycle times is probably the one that mechanically.

Speaker Change: Effects forward guidance the most.

Speaker Change: But there is a bit of a mix there.

Speaker Change: What we're seeing going forward is that not a worsening in fact again, we don't have enough data on the cycle time issue to suggest that we're being overly conservative but we're at a minimum confident that we've hit steady state. There is some reason to believe it might be a bit conservative I mentioned earlier in the call.

Doug Ingram: There's some reason to believe it might be a bit conservative. I mentioned earlier in the call, the first quarter had the most severe flu season, I think in 15 years, and that caused some delays. There's the typical insurance changes that occur in the first quarter of every year, that causes some delays. There's a thesis that may be embedded in this four to six weeks additional cycle time might be some of those particular first quarter issues. But I think for planning purposes, we're assuming, and I certainly think you should also assume that we're at steady state for the year.

The first quarter had the most severe flu season, I think in 15 years and that caused some delays. There is the typical insurance changes that occur in the first quarter of every year that causes some delays.

Speaker Change: Thesis that maybe embedded in this four to six weeks.

Speaker Change: Additional cycle time might be some of that those particular first quarter issues.

Speaker Change: Issues, but I think for planning purposes, we're assuming and I. Certainly think you should also assume that we are at steady state for the year a lot of work to do we're trying to do it.

Doug Ingram: We've got a lot of work to do. We're trying to do it even more efficiently, but I don't think we should assume that we will. On the safety event, the issue, of course, to remember is that when the safety event occurred, it was right before March. So right at the last month of the quarter. So of course, those who needed additional information were going to have delays, and that is going to flow through into the second quarter as well. So it shouldn't be at all surprising that the second quarter would be soft as a result of that.

Speaker Change: Even more efficiently, but I don't think we should assume that we will on.

Speaker Change: On the safety events the issue of course to remember is that in the.

When the safety event occurred it was right before March so right at the last month of the quarter. So of course, those who needed additional information.

Speaker Change: To have delays and that is going to flow through into the second quarter as well so it shouldnt be.

Speaker Change: At all surprising that the second quarter would it be soft as a result of that.

Doug Ingram: And so we're, of course, we're seeing that. And that's going to take some time. We need to get out there. We need to get to the broader community. As I've mentioned before, in my prepared remarks, when we get to folks, when the top thought leaders, which we were able to see right at the MDA conference when this all came out, it was quite clear that they were to a person, at least from my interactions with them, that didn't see this as changing their prescribing behavior at all. And we get the same answer when we talk to families.

Speaker Change: And so we're of course, we're seeing that and that's going to take some time, we need to get out there we need to get to the broader community as I've mentioned before.

Speaker Change: In my prepared remarks, when we get to folks when they're at.

Speaker Change: The top thought leaders, which we were able to see right at the MBA conference. When this all came out it was quite clear that they were to a person at least from my interactions with them, but didn't see this isn't changing there.

Speaker Change: Prescribing behavior at all and we get the same answer when we talked to families. We just need to get out some more and more families.

Doug Ingram: We just need to get out to more and more families. If you wanted to say, what are the signals kind of, as we see here today, the signals are, I guess what you would call the green shoots, because we are seeing, you know, start forms are coming in. I can't give you a split right now, but start forms are coming in both for ambulatory and non-ambulatory right now. So I think, you know, we are seeing the, as we communicate and we, as we talk and as we educate, we're seeing that occur. And over time, there should be no difference in the reaction to this, depending on whether you're ambulatory or non-ambulatory, because as you saw, and as Dr. Luis-Rodino-Klebek showed you, in fact, the data is quite clear that this minority of patients that get liver enzymes, it doesn't occur in any greater amount or any more severity, either on liver enzymes or bilirubin on non-ambulatory versus ambulatory patients.

You wanted to say what are the signals kind of as we sit here today the signals are or I guess, what you would call the green shoots because we are seeing.

Speaker Change: Start forms are coming in I can't give you a split right now but start forms are coming in both for ambulatory and non ambulatory.

Speaker Change: Right now so I think we are seeing the.

Speaker Change: As we communicated we as we talk as we educate we're seeing that occur and over time, there should be no difference in the reaction to this depending on whether you're <unk>.

Speaker Change: <unk> are non ambulatory because as you saw and as Dr. Louise Rodino <unk> showed you in fact, the data is quite clear that the.

Speaker Change: The.

Speaker Change: This is a minority of patients that get liver enzymes it doesn't occur in any greater amount or any more severity.

Speaker Change: Either on liver enzymes or bilirubin on non ambulatory versus ambulatory patients. So I would say.

Doug Ingram: So I would say, you know, we're seeing positivity when we actually get out there and we educate. We've got a lot of work to do over the course of this year to get to those, to the secondary sites, where there is capacity. One of our, as I said earlier, one of our significant issues is we've been very, very successful with the big thought leaders. Those sites are often fully booked, so we really need to get to other sites and make sure that we are getting people to sites that have capacity, and we need to get more education out there, both to those physicians and to the broader family community, and then we'll continue to work on cycle time.

Speaker Change: We're seeing positivity, when we actually get out there and we educate and we've got a lot of work to do over the course of this year to get to.

Speaker Change: Secondary sites, where there is capacity one of our.

Speaker Change: Said earlier, one of our significant issues as we've been very very successful with the big thought leaders, but those sites are.

Speaker Change: Often fully booked so we really need to get to other sites and make sure that we're getting people to sites that have capacity and we need to get.

Speaker Change: More education out there both to those physicians and to the broader family community and then we will continue to work on cycle times.

Unknown Executive: Thank you. One moment for our next question.

Speaker Change: Thank you one moment for our next question.

Ritu Baral: Our next question comes from Ritu Baral of TD Cowling, 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, 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?

Speaker Change: Our next question comes from the line of Ritu barrage of Cowen. Your line is now open.

Ritu Barage: Good afternoon.

Speaker Change: Hey, guys. Thanks for taking the question, Doug I want to follow up on that last phrase that you mentioned, how do you direct.

Speaker Change: Direct patients to those sites with more capacity are we talking like.

More community sites and why aren't these sites sort of add capacity like the main center since it a staffing issue is it a demand issue.

Speaker Change: How do you plan on doing that.

Doug Ingram: And is this the point where you think about opening more sites? I don't think as we sit here today that it's a number of sites issue, I think it's a focus. So really, the issue is, and it should be of no surprise, when you first launch a therapy, we really prioritize the big sites with the real thought leaders with a lot of experience and a lot of start forms, and we've just spent a lot of time there. We've spent, obviously, time on other sites, and they're all well-trained, but we haven't spent as much time there with a lot of the good educational work that we need to do, including responding to this most recent safety event, but even beyond that, and frankly, in a more positive note, really getting out and talking about the brilliant data that came out on the crossover.

Speaker Change: To the point, where you think about opening more sites.

Speaker Change: I don't think as we sit here today that is a number of sites issue.

Speaker Change: I think its a focus issue.

Speaker Change: So really the issue is it should be of no surprise. When you first launch a therapy, we really prioritize the big sites with the real thought leaders with a lot of experience.

Speaker Change: And a lot of start forms and we just spent a lot of time. There. We've spent obviously time on other sites and they're all well trained but we haven't spent as much time, there with a lot of the good educational work that we need to do including.

Speaker Change: Responding to this most recent safety event, but even beyond that and frankly in a more positive note really getting out and talking about the brilliant data that came out on the crossover remember that data is just lights out I mean, it's the.

Doug Ingram: Remember, that data just lights out. It's the kids on the therapy for two years were statistically significantly better than natural history on every single functional measure. The even at the one year mark when you get to the older ages, because of course, the kids dosed in the second phase of the trial were older. Now now they're in the decline phase, which is one of the problems with our original study as it relates to NSA. They're significant statistically on every measure, including NSA. And then you saw the trajectory analysis. And then you saw the muscle MRI.

Speaker Change: Kids on the therapy for two years were statistically significantly better than natural history on every single functional measure the even at the one year Mark when you get to the older Ages because of course, the kids dosed in the second phase of the trial, where older now now they are in the decline phase, which is one of the problems with our original.

Speaker Change:

Speaker Change: The study as it relates to NSA there significant statistically you can give on every measure including NSA and then you saw the trajectory analysis and then you saw the muscle MRI I do want to linger on their muscle MRI that is that's a really powerful thing I think there was probably a moment when some of US wondering whether you would actually be able to see in one year.

Doug Ingram: I do want to linger on that muscle MRI. That is a really powerful thing. I think there was probably a moment when some of us wondered whether you would actually be able to see in one year a really significant difference in muscle quality. Well, you do across significant number of muscles. You see this very different result where kids that have been dosed with the Levitas have their muscle preserved and much less fat and fibrotic tissue. And kids that didn't get dosed a year later are missing a lot of that muscle and have a lot of infiltration of fat and fibrotic tissue.

Speaker Change: Year of really significant difference in muscle quality, what you do across a significant number of muscles. You see this very different result, where kids that have been dosed with <unk> have their muscle preserved and much less fat in fibrotic tissue in kids that didn't get dosed a year later or missing a lot of that muscle.

Speaker Change: We have a lot of infiltration of fat in fibrotic tissue, we see to get all of that information and have those conversations with those secondary sites.

Doug Ingram: We need to get all of that information and have those conversations with those secondary sites. What we can't do in any real way or in any thoughtful way is to redirect people's start forms from one site to another. That's really not possible. What we can do is really spend a lot of time with them, spend a lot of energy with them, and spend a lot of education with them, as well as making sure that we're educating the patient community across the United States. I think it is going to create significant dividends, both I think for us and our revenue, but far more important than that, getting kids.

Speaker Change: We can't do it.

Speaker Change: A real way or in a thoughtful way sort of redirect people's.

Speaker Change: Start forms from one site to another thats really not possible. What we can do is really spent a lot of time with them has been a lot of energy with them and spend a lot of education with them as well as making sure that we're educating.

Speaker Change: The patient community across the United States and I think it is going to.

Speaker Change: It is going to going to create.

Speaker Change: We have significant dividends.

Speaker Change: I think for us in our revenue, but far more important than that getting kids infused that are going to benefit from this life changing therapy.

Doug Ingram: Thank you for your questions. Thank you.

Ritu Barage: For your questions Ritu.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you one moment for our next question.

Louise Chen: Our next question comes from 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 Elevitus represent? And also, are you planning or expecting that sales will recover starting in the third quarter? So, two answers to that. Obviously, we're pulling our guidance down, you know, primarily, well, exclusively, really, from a Levitas, so you can do the math on that. This is an Elevitas-related issue. And then, yeah, we are assuming, starting in the summertime and starting really in the second half of the year, that we're going to see a significant uptick.

Speaker Change: Our next question comes from the line of Louise Chen of Scotiabank. Your line is now open.

Louise Chen: Hi, Thanks for taking my question here I wanted to ask you out of the new guidance you gave what percent of sales of <unk>.

Louise Chen: It represented and also are you planning or expecting that sales will recover starting in the third quarter. Thank you.

Louise Chen: So.

Louise Chen: Two answers to that obviously, we're pulling our guidance down primarily.

Louise Chen: Exclusively really from <unk>. So you can do the math on that this isn't a <unk> related issue.

Louise Chen: And then yes, we are assuming starting in the summertime 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.

Doug Ingram: We're already seeing, you know, again, using a hackneyed phrase, the green shoots of that. But, you know, what we really do know, and 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. A lot of times, people have to travel with this therapy. There are, you know, other, you know, 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 and across the back half of the year as we execute.

Louise Chen: <unk> <unk>, the green shoots of that but what we really do know because we've talked 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, while it sometimes people have to travel with this therapy there are other.

Louise Chen: 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 and across the back half of the year as we execute.

Doug Ingram: And we will, actually. Yeah, very specifically, we gave guidance of $900 million for our PMO, we maintain the guidance of $900 million from our PMO franchise. So the revision in our total net product revenue was all related to 11.

Louise Chen: And we will execute.

Louise Chen: Yes, very specifically.

Louise Chen: We gave guidance of $900 million.

Louise Chen: For our PMO, we maintain the guidance of $900 million from our PMO franchise. So the revision in our total net product revenue was all related to a level.

Unknown Executive: Thank you.

Andrew Tsai: One moment for our next question. And our next question comes from the line of Andrew Tsai of Jeffries, your line is now open. Hi, thanks for taking my...

Louise Chen: Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of Andrew Tsai of Jefferies. Your line is now open.

Louise Chen: Hi.

Louise Chen: Thanks for taking my.

Doug Ingram: My question is around this, you know, following this patient death, some investors are wondering about a worst case scenario where a lividus is pulled from the market, something more drastic, basically, but then 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 DMT? Thanks. Sure.

Louise Chen: My question is around.

Speaker Change: Following this patient death. Some investors are wondering about a worst case scenario, where <unk> is pulled from the market something more drastic basically but then 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.

Louise Chen: Do have an accelerated approval and the non ambulatory DMD.

Louise Chen: Sure sure, but first on the appointment I wanted to be clear I am not going to obviously comment on any particular appointment, which we just got news of today.

Doug Ingram: But 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. And there's no reason to believe that that should change or that anyone would permit that to change. I would remind you, as relates to Levitas, the evidence for its approval was brilliant at the time, absolutely remarkable, and then it only got more impressive over time.

Louise Chen: 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 I know there is no reason to.

Louise Chen: Believe that that should change or that anyone would permit that to change I would remind you as it relates to <unk>.

Louise Chen: The evidence for its approval was brilliant at the time.

Louise Chen: Absolutely remarkable and then they 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 then thereafter, we had the crossover data that we unblinded all pre specified every week.

Doug Ingram: 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 then thereafter, we had the crossover data that we unblinded, all pre-specified, 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 Levitas has one of the most impressive safety profiles in the context of AAV-mediated gene therapy that has ever existed.

Louise Chen: <unk> measure was strongly statistically positive the muscle MRI is brilliant.

Louise Chen: Theres 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 <unk> has one of the most impressive safety profiles.

Louise Chen: 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.

Doug Ingram: 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 a remediated 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.

Louise Chen: With respect to us they are particularly rare in fact this one incident.

Louise Chen: Is <unk>.

Louise Chen: Unique not only in its its outcome, but even in the sort of the course of it theres some something very different about it and it's in the context of AAV mediated gene therapy, it's in the context of the understanding.

Louise Chen: That there is always a risk of elevated liver enzymes in the vast majority of cases, where 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.

Doug Ingram: They respond very rapidly to a modest increase in steroids and come back down to baseline. 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 approved this brilliant therapy.

Louise Chen: Regulators would be considering anything other than the fact that they should be proud that they approve this brilliant.

Louise Chen: Therapy.

So.

Unknown Executive: Thank you. One moment for our next question.

Louise Chen: Thank you one moment for our next question.

Louise Chen: Yeah.

Eliana Merle: Our next question comes from line up Eliana Merle of UBS, your line is now open. Hey guys, thanks for taking the question. Just in terms of the potential label update for Levitas, 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.

Speaker Change: Our next question comes from the line of coming on MRO of UBS. Your line is now open.

Louise Chen: Hey, guys. Thanks for taking the question just in terms of the potential label update for <unk> can you talk us through your latest expectations there for any potential update or conversations with the FDA. After the patient that I guess when could we potentially.

Louise Chen: Potentially hear about a label update and what your expectations are for what that could look like.

Louise Chen: And then just in terms of the commercial uptake you mentioned that there are some patients who are scheduled for late March that delayed their dosing what.

Doug Ingram: What proportion of those have now rescheduled their infusions? 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 you know, they're coming up to an infusion in a week, and so, you know, they had to, you know, either pause or, you know, most likely in almost every case, reschedule immediately so they could get access to that information.

Louise Chen: What proportion of those have now reschedule out there. Thanks.

Louise Chen: Thanks.

Louise Chen: So.

Speaker Change: Let me answer the second question first by simply telling you. They 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 events needed information.

Speaker Change: And they're coming up to an infusion in a week and so they had to.

Speaker Change: Either pause or more most likely in almost every case reschedule immediately so they could get access to that information as it relates to your first question I will turn the call.

Louise Rodino: As 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 ALS. And so 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.

Speaker Change: Paul to Louisa can provide an update on the label update.

Speaker Change: Sure and in April we submitted a labeling supplement we already had one planned and anticipated and so at that time, we also updated its label.

Speaker Change: To include this pay.

Speaker Change: A patient death.

Speaker Change: I can't Oh Wow.

Speaker Change: And so SBA confirmed receipt of that and set a target review date. So the target completion date will be no later than the fourth quarter of this year for the label update.

Unknown Executive: Thank you.

Brian Abrahams: One moment for our next question.

Speaker Change: Thank you Amit for next question.

Unknown Executive: Our next question comes from Brian Abrahams of RBC Capital Markets, and the line is now open.

Speaker Change: Our next question comes from the line of Brian Abrahams.

Speaker Change: B C capital markets. Your line is now open.

Speaker Change: 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 TUI and then I guess onto we is the emerging data still expected to be disclosed public.

Speaker Change: By the Middle of 2025, where 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.

Unknown Executive: I'm going to turn this over to Louise, but let me briefly say the following regarding our interactions with OTP in 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.

Speaker Change: I'm going to turn this over to Luis but let me briefly say the following regarding our interactions with L. P. P and the LG L. G. M D portfolio. So since the change in administration, we have had a number of discussions with otp.

Speaker Change: Otp and interactions everything has remained on course.

Speaker Change: The approach that they had previously.

Speaker Change: Confirmed with US is the approach that they've taken today. So nothing has changed there which is all very positive and I would also say I know theres 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 3500.

Doug Ingram: And 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 downs of 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. Verdun. Things seem to be quite on track, and certainly the approach that they were historically taking is the approach they're taking today.

Speaker Change: Les Austin that there may be as a result of that delays or slowing downs of reviews, but I must give credit where credit is due we have not yet seen that at all with our colleagues over at OTT led by Dr ever done things seem to be quite on track and certainly the approach that they were historically, taking the approach they're taking today.

Louise Rodino: 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 OTC, 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 2C. So things are progressing as planned with the agency.

Luis: But luis Youre going to want to provide more color about that.

Luis: Sure as we've seen over the past several weeks, we've seen consistent interactions with with Otp as they've seen previously we've had a number of interactions. So on line three with all three.

Luis: As noted they confirmed the approval.

Luis: Accelerated approval pathway with open just as early as last week they accepted.

Luis: A rolling review for SRP, nine threats arthritis, and things continue to progress as planned.

Luis: Also as we announce the same review division.

Luis: Cleared the IND for SRP 9305, French for QC.

Luis: Things are progressing.

Luis: As planned with the agency.

Unknown Executive: Thank you. One moment for our next question.

Luis: Thank you one moment for our next question.

Deb Jade: Our next question comes from the line of Deb Jade of Guggenheim Securities. Your line is now open. Hey, good afternoon, and thanks for taking my questions.

Speaker Change: Our next question comes from the line of <unk> <unk> of Guggenheim Securities. Your line is now open.

Speaker Change: Hey, good afternoon, and thanks for taking my questions.

Unknown Executive: So a couple of questions on one on Lemgurl. Is there a threshold for protein expression that the ODP wants? And number two, could you sort of quantify the number of non-ambulant boys who have been treated on the commercial inhibitors product? Thank you.

Speaker Change: Couple of questions on one on limb girdle is there a threshold for protein expression.

Speaker Change: Would it be wants to see.

Speaker Change: And number two could you sort of quantify the number of non ambulant boys, who have been treated on the commercial but this product. Thank.

Speaker Change: Thank you.

Louise Rodino: 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 STAR forms for non-ambulatory kids.

Speaker Change: On the second question, we're not providing that level of data, although I will tell you. We've obviously historically been dosing Nonambulatory kids, we are continuing to dose Nonambulatory kids.

Speaker Change: And we're getting start forms for non ambulatory kits on the first question I will turn.

Louise Rodino: On the first question, I will turn that question over to Louise Rodino-Klepper. Sure, and I think I forgot to answer the question in the previous time about, we will have the MR gene data in the first half of this year, which will go into the, into the BLA, and that will be expression of basal glycan protein 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 the high dose, around the 50% mark. We know from preclinical data that much lower expression leads to functional benefits.

Speaker Change: <unk> over to Luis Nieto, Quebec.

Speaker Change: Sure.

Speaker Change: I forgot to answer the question on a previous time about we will have the encouraging data in the first half of this year, which will go on to that until the BLA that will be expression of this article I can't protein.

Speaker Change: On the question around expression levels as you know from the.

Speaker Change: 101 trial, we saw expression levels with both doses, but the low and high dose.

Speaker Change: Around the 50% Mark.

We know from preclinical data that much lower expression leads to functional benefits.

Louise Rodino: So we anticipate the results that we see from MR gene will be consistent with that and will certainly lead to functional benefit and above any threshold of relevance.

Speaker Change: I anticipate the results that we see from our emerging will be consistent with that.

Speaker Change: And we will certainly lead to two functional benefit and above any threshold does irrelevant.

Louise Rodino: And just to Ted's 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 setting. So we've had good experience. I think our enrollment forms, our start forms, are something like 40% non-ambulatory, 60% ambulatory.

Speaker Change: And so thats. Its first first question around the number of non ambulant patients I think we have previously disclosed that it's well over 100 patients between clinical and commercial settings. So we've had good good experience there.

Speaker Change: I think our enrollment forms our start forms are something like 40% non ambulatory 60% ambulatory.

Unknown Executive: Thank you.

Salveen Richter: One moment for our next question.

Speaker Change: Thank you one moment for our next question.

Louise Rodino: 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 Exxon Skipping franchise, but also Elevitus? Thank you. The confirmatory trial for, oh, okay, I guess you mean the InVision trial.

Speaker Change: Our next question comes from the line of solving Ritchie of Goldman Sachs. Your line is now open.

Speaker Change: 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 <unk>. Thank you.

Speaker Change: The confirmatory trial for of it Okay. I guess, you mean, the envision trial Luis I'll turn this to you.

Louise Rodino: Louise, I'll turn this to you. for the last patient last visit for InVision was in 2027. Thank you.

Speaker Change: I just thought that the last patient last visit for vision 2027.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you one moment for our next question.

Brian Skorney: Our next question comes from a line of Brian Skorney of Barrett, your line is now open. Hey, good afternoon. Thanks for taking the questions. I guess just in regards to the changes that CBER and meetings with the FDA, you said that you're expecting a decision on labeling update to 11. It's no later than the fourth quarter.

Speaker Change: Our next question comes from the line of Brian Cornea of Baird. Your line is now open.

Brian Cornea: Hey, good afternoon, thanks for taking the questions I guess just in regards to the.

Speaker Change: James Thats Huber in meetings with the FDA, you said that Youre expecting a decision on labeling update to 11 US no later than the fourth quarter. I'm. Just wondering is there any sort of formal meetings that are held with <unk> along with that or is it just sort of an internal review until.

Louise Rodino: 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?

Doug Ingram: And then when we first heard about the patient death, I know there's a complicating factor with the reactivation of latent virus. I was just wondering if there wound up being a biopsy and if you had anything informative on that.

Speaker Change: It may make that decision and then when we first heard about the patient I know theres, a complicating factor with reactivation of latent virus I was just wondering it wound up being a biopsy and if you had anything informative on that front.

Doug Ingram: 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 two. They may or may not be additionally informative.

Speaker Change: I'll answer the last part of it they get easier on Luis we don't have we don't have the autopsy results yet.

Speaker Change: We are waiting for them, we should get them in the next month or two.

Speaker Change: They may or may not be additionally, informative.

Louise Rodino: 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. And really, it's more of a finalizing the label update. It's not necessarily that we're awaiting a decision on it. So they've already confirmed that they're in general agreement. So it's really just going through the process. Thank you.

Speaker Change: And as to the first of your questions I'll turn this to Luis.

Speaker Change: Yeah.

Speaker Change: Regarding the label update.

Speaker Change: Okay, I will just come back with any questions along the way and that's needed and really it's more of a finalizing the label update it's not necessarily that we're awaiting a decision on it. So they are already confirmed.

Speaker Change: That they were in general agreement. So that's really just going through that process now.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you Amit for next question.

Mike Ulz: Our next question comes from the line of Mike Ulz of Morgan Stanley, your line is now open. Good afternoon, and thanks for taking the question. Maybe just another one on levitist trends and more recently, just curious if there's been a shift in the age of the patients being treated or Ambulatory status of those patients being 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 anecdote than precise, you know, trending, is that we are continuing to see both ambulatory and non ambulatory start forms coming.

Michael Hill: Our next question comes from the line of Michael of Morgan Stanley. Your line is now open.

Good afternoon, and thanks for taking the question maybe just another one on <unk> trends and more recently just curious if theres been a shift in the age of the patients being treated or.

Michael Hill: In the ambulatory status of those patients being treated thanks.

Michael Hill: Yes. 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 anecdote than precise trending.

Michael Hill: Is that we are continuing to see both ambulatory and non ambulatory start forms coming in.

Doug Ingram: So, you know, 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 non-ambulatory from a start.

Michael Hill: 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 them.

Michael Hill: Good uptake in both ambulatory and non ambulatory from a historical perspective.

Doug Ingram: And I will say, let me let me forecast the future of it. 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 that there is no different. and any of the markers. Any of the elevated liver enzyme markers, any of the Billy Rubin marker, there is no difference between ambulatory and non-ambulatory in, for instance, you know, risk of elevated liver enzymes or liver injury. So there really should be no If we educate properly, why, there would be significant... Thank you.

Michael Hill: And I will say, let me, let me forecast the future of it of course, the real issue is what happens when the information gets out to patients and one of the things I want to remind us about is dead.

Michael Hill: But there is no difference in any of the markers any of the elevated liver enzymes markers any of the bilirubin marker. There is no difference between.

Ambulatory and non ambulatory and for instance risk of elevated liver enzymes liver injury. So.

Michael Hill: It should be no reason, if we educate properly why there would be a significant difference and start ups.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you Mohammed for next question.

Gil Blum: Our next question comes from the line of Gil Blum of Neumann Company, 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, you know, took a minute to think about whether to go on treatment post the event. Was there any commonality across them, you know, more ambulatory, non-ambulatory, or was just the timing thing? Thank you.

Speaker Change: Our next question comes from the line of Gil Blum of Needham <unk> Company. Your line is now open.

Gil Blum: Good afternoon, and thanks for taking our question, maybe a different approach for kind of the.

Gil Blum: The same topic as it relates to the patients who are kind of.

Gil Blum: Took a minute to think about whether to go on treatment post the event.

Speaker Change: Was there any commonality across them.

Speaker Change: Tori on both or was just a timing thing. Thank you hi, so.

Doug Ingram: Hi, I'm sorry to interrupt you, Gil. Timing, just the timing. They were in March, and that was the approximating very end of February, early March was the announcement. Thank you.

Speaker Change: So I'm sorry to interrupt you go timing, it's just a timing thing.

Speaker Change: Yeah, they were remarks.

Speaker Change: And that was it.

Speaker Change: I think very end of February early March was the announcement.

Speaker Change: Hmm.

Joe Schwartz: One moment for our next question.

Speaker Change: Thank you Mohammed for next question.

Doug Ingram: Our next question comes from the line of Joe Schwartz of Living 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? And I know that there's an upcoming annual conference in June. So I'm wondering, you know, what are the company, what's the company's plan now to interact with these organizations? And what do you think you need to emphasize with these families in order to underscore the positive risk benefit of a Levitas?

Speaker Change: Our next question comes from the line of Joe Schwartz of Leerink Partners. Your line is now open.

Speaker Change: Thanks, very much we noticed the company recently hosted a meeting with P. P. M D. After the patient I'm just wondering.

Speaker Change: How impactful.

Speaker Change: Were these interactions and.

Speaker Change: I know that there is an upcoming annual conference in June So I'm wondering what are the company the company's plans now too.

Speaker Change: Interact with.

Speaker Change: These organizations and what do you think you need to emphasize what these families in order to.

Speaker Change: Underscore the.

Speaker Change: Positive risk benefit of a limit us.

Doug Ingram: 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's some 10, 12, 13,000 Duchenne patients in the United States. And we need to get the information out to that broad community so they can make intelligent decisions and evidence-based decisions with their physicians. At the same time, by the way, side note, we have to do the same thing with the physicians because the physician is the ultimate guider for the decisions of the families. And 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 it.

Speaker Change: Yes, I mean, I think that webinar was very meaningful but it's not yet I think we are committed to giving the broad community Roemer Theres. Some 10, 12 13000 duchenne patients in the United States and.

Speaker Change: And we need to get the information out to that 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 Guy.

Speaker Change: <unk> for the decisions of the families and the information that we have to get out to the world is both the safety profile file of this therapy, but also the efficacy profile of this therapy, we can't leave one behind because you 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 <unk>.

Doug Ingram: You can't leave one behind because you 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 Elevitas 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.

Speaker Change: Because of the amount of data, we have and the fact that that data has come in.

Speaker Change: Over a significant period of time I, sometimes worry that people are seeing.

Speaker Change: All of the information and all of the evidence of the benefits of 11 is together because it's really impressive package that.

Speaker Change: Think to any rational physician.

Speaker Change: We'll indicate that this therapy is a significant disease modifier that has the.

Speaker Change: Potential for.

Speaker Change: Stopping the ferocious muscle damage.

Speaker Change: Or at least a significant amount of the.

Speaker Change: The muscle damage and then slowing or fully arresting the decline that is inevitable with duchenne.

Doug Ingram: For anyone that doesn't get treatment. So 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, the context of all the safety and the efficacy available to us. And we are Committed to doing. Thank you.

Speaker Change: For anyone that doesn't get treatment. So 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 the recent webinar of course was sharing the most recent information about the safety of that I think that was.

Speaker Change: Extraordinarily appropriate on a go forward basis, we need to talk about all of it in context of all the safety and the.

Speaker Change: The efficacy available to us and we are committed.

Speaker Change: Committed to doing that.

Unknown Executive: One moment for our next question.

Speaker Change: Thank you one moment for our next question.

Iana Zhu: Our next question comes from the line of Iana Zhu of Wells Fargo, your line is now open. Great. Thanks for taking our questions. 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 indicator 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 are seeing a pickup in pace of the patient start forms coming in towards the more recent period?

Speaker Change: Our next question comes from the line of Xu of Wells Fargo. Your line is now open.

Xu: Great. Thanks for taking our questions first.

Xu: I'd like to ask for a clarification clarification question regarding the uptick that you anticipate in the summertime for patient demand based on some leading indicators you're seeing.

Xu: And the question is the must also be leading indicator.

Xu: Some decline in that.

Xu: <unk>.

Xu: Youre lowering guidance, how do we reconcile a.

Xu: A decline and also an uptick could we assume that you are seeing.

The.

Xu: Pick up in pace.

Xu: Patients start forms coming in towards the more recent period.

Iana Zhu: And then, sorry about that long-winded question.

Xu: And then sorry about that long winded question.

Doug Ingram: A follow-up is a straightforward question about peak sales estimate. Do you have any comment on, you know, whether you're 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 both. 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 event and the need to get more information to patients, we saw a drop-off. Now, when we say we're already seeing an uptick and we're going to see a more significant uptick in the summer.

Xu: A follow up too much.

Xu: My follow up question about peak sales estimate do you have any comment on.

Xu: Whether you're changing your guidance on the peak sales and the time to reach that peak. Thank you.

Xu: Yes.

So on your first question both are great questions. Let me answer both 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 the initial.

Xu: Now when we say, we're already seeing an uptick and we're going to see a more significant uptick in the summer.

Doug Ingram: . Well see so you know, 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 caused it as we're getting that information out, we're already seeing that uptake and start forms. And then when we talk to those families but also sites. Quite clear that there is a belief among everyone that they're going to see a very significant uptake in the summertime when you get past the school year and some of those issues.

Xu: That's because that's what we're seeing so someone asked earlier.

Xu: Why are you assuming a flat to down in second quarter. It's because this is a long cycle time therapy.

Xu: And a lot of people need more information to contextualize things and that caused it as we're getting that information out we're already seeing.

Xu: That uptick in start forms and then when we talk to those families. But also sites. It's quite clear that there is a belief among everyone that youre going to see a very significant uptick in the summertime when you get pass the school year and some of those issues.

Doug Ingram: So I hope that answers your question.

So I hope that answers your question so.

Doug Ingram: So the second issue is on peak your sales. So we're not prepared yet to talk about peak your sales, but I want to put the concept of peak your sales in the context of a one-time therapy. Unknown Speaker Normally peak your sales is an indication of the ultimate opportunity of the therapy and one time therapy is different. It's an under the it's it's essentially area under the curve. So, you know, how long it takes to get to peak and it will change the actual peak, but the same opportunity exists essentially under the curve. And there is 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 these, you know, some of it being cycle time, some of being some educational needs, some of it being some imbalances and sites that we need to address.

Xu: The second issue is on peak yourselves. So 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.

Xu: Normally the peak year sales is an indication of the ultimate opportunity of a therapy and onetime therapy. It's different it's an under that it's essentially area under the curve analysis.

Xu: So you know how long it takes to get to peak and.

It will change the actual peak, but the same opportunity exists essentially.

Xu: Under the curve and there is 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 these some of it being cycled time some of them being some educational needs some of it being some imbalances in sites that we need to address the ultimate opportunity <unk>.

Doug Ingram: 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 this is amenable to. And so the same opportunity exists. What that, what a delay and uptake implied by the $500 million delta in our guidance implies and what that means for peak year sales is something we'll have to calculate and then look at and talk later, maybe later this year, maybe early next year. But the opportunity remains the same. The same ultimate NPV should exist in a year.

Xu: The same we are correct and our epidemiology, we know the patient population and the size of it.

No reason to believe there is any.

Xu:

Xu: Smaller population that this is amenable to and so the same opportunity exists.

Xu: What a delay in uptake implied by the $500 million.

Xu: Delta in our guidance.

Xu: Implies and what that means for peak year sales is something we will have to calculate and then look at 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.

Unknown Executive: Thank you.

Unknown Executive: One moment for our next question. And our next question comes from Lin 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 Elevity's ex-US sales quarter over quarter and to what extent those three headwinds you mentioned for US may also apply ex-US at least anecdotally? Thank you.

Speaker Change: Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of cost Us <unk> <unk> of BMO capital markets. Your line is now open.

Speaker Change: Hi, Thanks for taking a question too.

Speaker Change: To the extent you can comment on thought can you talk a little bit about the decline of <unk> ex U S sales quarter over quarter and to what extent those three headwinds you mentioned for the U S mail supply ex U S at least anecdotally things.

Unknown Executive: Well, I'm, I'm hesitant to, to discuss our partner's 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, I would have to beg off that question and ask you to, to ask Roche about that. Thank you. One moment for our next question. And our next question comes from a line of Anupam Rama of J.P. Morgan, the line is now open. Anupam, your line is now open.

Speaker Change: Right.

Speaker Change: I'm hesitant to to discuss our partners.

Speaker Change: 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.

Speaker Change: We'd have to beg off that question and ask you to.

Speaker Change: To ask Roche about that.

Speaker Change: Thank you for our next question.

Speaker Change: And our next question comes from the line of a new pump promo of Jpmorgan. Your line is now open.

Speaker Change: Your line is now open.

Doug Ingram: Oh, sorry about that. Thanks 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 The information around this particular case previously, it was just around ALI, so now this included ALS and the case.

Speaker Change: Oh, sorry about that thanks, so much for taking the question guys. Just a quick clarification question.

Speaker Change: Luis I think you said.

Speaker Change: In April you submitted a labeling update and had some of the patient.

Speaker Change: You knew about the patient deaths information, but what else was included within that labeling update and it includes the two year embark safety update that include any real world.

Speaker Change: Safety updates what al was included in that.

Speaker Change: Right.

Speaker Change: This is just they are betting their safety information.

Speaker Change: Including.

Speaker Change: The information around that particular case previously.

Speaker Change: It's just around ally. So now that's included Ala and <unk> in.

Doug Ingram: So that was the breadth of the episode. Thank you. One moment for our next question. And our next question comes from the line of Biren Amin of Piper Stanley. 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 do you think it was more driven by patients being more cautious and need more hand-holding before they sign up for administration?

Speaker Change: In the case that was that the breadth of the epic.

Speaker Change: Thank you for our next question.

Speaker Change: Our next question comes from the line of Pirate Aman of Piper Sandler Your line is now open.

Pirate Aman: Yeah, Hi, guys. Thanks for taking my question.

Pirate Aman: At the end of February the company mentioned on.

Pirate Aman: The year end call that there was ample capacity for both infusion and follow up so I just wanted to ask how site capacity change over the last two months.

Pirate Aman: Or what do you think it was more driven by patients being more cautious and need more handholding before they sign up for administration.

Doug Ingram: 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, Tazeen Ahmad, Biren Amin, Tim Lugo, Ritu Baral, Brian Abrahams, Uy Ear, Salveen Richter, Gena Wang, Mary Jenkins, Kostas Biliouris, Samantha Corwin, Dallan Murray, Mike Ulz, Danielle Bongero, Tommie Reerink, Gavin Clark, Ry Forseth, Robert Finke, Brian Skorney, Absolutely.

Pirate Aman: On that last point is there anything the company can do to provide risk mitigation strategies to physicians given I think we can be looking for clarity that wood.

Pirate Aman: Future events.

Pirate Aman: Let me say a couple of things one we do in aggregate have good site capacity. The issue that we have as I've mentioned in my opening remarks is a bit of an imbalance where if you just focus on the top size by the way.

Pirate Aman: The top sites are responsible for about 60% of our current sales.

Pirate Aman: They have they've been so sufficiently successful and enthusiastic along with their patients that they're often booked all the way out some are booked a year or more out. So it's not simply about capacity because we can't let's be clear you can't read redirect a start form that sitting at.

Pirate Aman: This site acts that's got a one year delay to cite why over in filling the blank Indiana.

Pirate Aman: It's just sitting there so we've got to make all of the sites more productive which is on US we got to get out and educate work with them and the like and so that's the issue.

Pirate Aman: Do I think that there was some.

Pirate Aman: Drop off in March from families that you would say handholding in my view would be needed 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.

Doug Ingram: 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 laudable safety profile therapy. Let me be very clear. We proactively placed into the label a significant amount of monitoring, which physicians follow. We have this concept called Sarept Exchange, which is really one of a kind where physicians in any site can get access to some of the world's leaders.

Pirate Aman: And then on risk mitigation and I'll, just say, we have a wealth of risk mitigation and this very.

Pirate Aman: Laudable safety profile therapy, maybe very clear like we proactively placed into the label.

Pirate Aman: A significant amount of monitoring which physicians follow we have this concept called surround the exchange, which is really one of a kind where.

Pirate Aman: Physicians in any site can get access to some of the world's leaders.

Pirate Aman: Nearly on a real time basis to if they have questions or the like when they are infusing.

Doug Ingram: I think the thing that's going to give people the greatest confidence is that they're going You know, the safety event that we saw earlier this year. is a tragic one for that family, no doubt, it's horrible. But that is in the context of AAV gene, mediated gene therapy generally. And it has to be put in context of the number of patients that we've dosed. I mean, it would remind. We hear often of people that announce data, one patient or two patients or three patients. We've dosed well over 800 patients. Generally speaking, we know the safety profile of this therapy.

Pirate Aman: I think the thing thats going to give people.

Pirate Aman: The greatest confidence.

Pirate Aman: Is the data itself because.

Pirate Aman: The safety event that we saw earlier this year.

Pirate Aman: Was the tragic one for that family no doubt sharp.

Pirate Aman: But that is in the context of AAV gene mediated gene therapy generally and.

Pirate Aman: It has to be put in context of the number of patients that we've dosed I mean, I would remind you that.

Pirate Aman: We hear often have people announce data one patient or two patients or three patients we've done well over 800 patients. So generally speaking we know the safety profile of this therapy. If something comes out there is going to be an autopsy that's going to that we're going to have access to in the next couple of months and if something comes out there that can provide additional.

Doug Ingram: If something comes out, there's going to be an autopsy that 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, you know, 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 the experts, of which I am not one, are, you know, not yet confident that there'll be something out of the autopsy that will provide additional insight.

Pirate Aman: The land site 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.

Pirate Aman: Obviously, that's enlightening will certainly bring it to the community.

Pirate Aman: I think the experts of which I am not one.

Pirate Aman: Are you know not not yet confident that there'll be something out of the autopsy that will provide additional insight and I think the greatest insight that families can have to make risk based decisions just to understand this therapy. What it can do for these families. How it can protect muscle and on the other side what are generally laudable safety profile. It has in the <unk>.

Doug Ingram: I think the greatest insight that families can have to make risk-based decisions is to understand this therapy, what it can do for these families, how it can protect muscle, and on the other side, what a generally laudable safety profile it has in the context of, you know, serious AAV-mediated gene therapy. Thank you. One moment for our next question. Our next question comes from the line of David Hoang of Dutch Bank, your line is now open. Hi there, thanks for taking the question. So I just wanted to ask one on, you know, any anecdotal experience broadly for patients that have been dosed to date with commercial elevatives, what you hear from the docs and families as a matchup with what you know from Embark and the clinical trial experience, and then just with the PMOs, how should we think about cannibalization of the products given how the elevatives commercial uptake curve may be changing?

Pirate Aman: Contextual serious AAV mediated gene therapy.

Speaker Change: Thank you Mohammed for next question.

Speaker Change: Our next question comes from the line of David Ho of Deutsche Bank. Your line is now open.

Speaker Change: Hi, there thanks for taking the questions.

Speaker Change: I just wanted to ask one on.

Speaker Change: Any anecdotal experience broadly for patients that have been dosed to date with commercial a lot of it is what you hear from the docs and families doesn't match up with what you know from embark into clinical trial experience and then just with the PMO.

Speaker Change: Can we think about cannibalization of the products given out.

Speaker Change: This commercial uptake curve may be changing thanks, a lot.

Doug Ingram: Thanks. Yeah. On the first one, you referenced that it's anecdotal. So take that with a grain of salt. It's anecdotal. Unfortunately, we don't get approvals on anecdotes, we get approvals on evidence. The anecdote's amazing. It's very clear. I mean, one of the things that during this very difficult and chaotic time that's existing in the broader market in biotech specifically, and certainly at Sarepta specifically, it is a comfort to me when I get videos from families. And we've got, you know, we're seeing a lot of extraordinary stories from families, kids that are, you know, riding bikes, kids are running up and down at an age when they ought to be in a power wheelchair, kids outpacing their father who's trying to catch them in the woods.

Speaker Change: Yeah on the on the <unk>.

Speaker Change: First one you referenced it is anecdotal.

Speaker Change: So take that with a grain of salt. It's anecdotal we don't Unfortunately, we don't get our Peru approvals, an anecdote, we get approvals on evidence the anecdotes amazing he's.

Speaker Change: Very clear.

Speaker Change: One of the things that during this very difficult and chaotic time, that's existing in the broader market in biotech specifically and certainly at <unk> at <unk>, specifically it is comfort to me when I get videos from families and we've got.

Speaker Change: So we're seeing a lot of extraordinary.

Speaker Change: Stories from families kids that are.

Speaker Change: Riding bikes kids are running up and down at an age when they ought to be in a power wheelchair kids outpacing their father who's trying to catch them in the woods. That's one particular individual or video I watch often.

Doug Ingram: Unknown Executive, Huidong Wang, Lin Tsai, Konstantinos Biliouris, Leo Watson, Sarepta Therapeutics Inc. So, you know, that doesn't mean much. It's only anecdote, but we get a lot of great anecdotes. I think when families begin to get the opportunity to talk to other families and see the experience they're having, you know, not only the experience of going through the process to get infused and the infusion process and the like, but then seeing what it may mean to them in their life going forward, I think it's going to be very, very motivating for families who, you know, as yet, maybe don't have a start for them.

Speaker Change: So.

Speaker Change: That doesn't mean much its only anecdote, but we get a lot of.

Speaker Change: A lot of great anecdote I think when families begin to offer 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.

Speaker Change: Be very very motivating for families who as yet maybe you don't have to start funding.

Unknown Executive: Thank you. One moment for our next question. One other thing I should say, I think there are some interesting information on that. and our website. Thank you. And our next question comes from a line of Mitchell Kapoor of HC Wim Wright and Co. Your line is now open. Good afternoon, this is Dan on from Mitchell. Thanks for taking our questions.

Speaker Change: Thank you one moment for our next question.

Speaker Change: One other thing I should say I think I think there are some interesting.

Speaker Change: Information on that.

Speaker Change: And our website I believe.

Speaker Change: Yeah.

Speaker Change: Thank you and our next question comes from the line of Mitchell Kapoor of HC Wainwright <unk> co. Your line is now open.

Speaker Change: Good afternoon. This is Dan on for Michel Thanks for taking our question. So we were wondering with the FDA changes specifically, Dr. Rene Prasad now homing fever, and given the expectation of having more data for approval how about your approach to clinical trial designs change and do you see any impact to your development timeline. Thank you.

Unknown Executive: So we were wondering with the FDA changes, specifically, Dr. Vinay Prasad, now homing CBER, and given his expectation of having more data for approvals, how might your approach to clinical trial designs change? And do you see any impact to your development timeline? Thank you. I can all let me speak to what we know today. Of course, that that appointment occurred only today. So what I can tell you is that, you know, subsequent to the change of, you know, Commissioner McCary, and then the departure of Dr. Marks, we've had a significant number of interactions with our primary reviewer on the biologic side.

Speaker Change: Let me speak to what we know today of course out of that appointment occurred only today. So.

Speaker Change: Well I can tell you is that some.

Speaker Change: Subsequent to.

Speaker Change: The change.

Speaker Change: Commissioner Macquarrie and then.

Speaker Change: The departure of Dr remarks.

Speaker Change: <unk> had a significant number of interactions with our primary reviewer on the.

Biologic side, which is OTT, it's cheaper and we have seen so far no changes in the approach. They are taking in fact, Dr. Overdone.

Doug Ingram: OTP at CBER and we have seen so far no change. Dr. Verdun appears to be quite innovative in her goal of moving therapies along and relying upon modern tools for drug development. I would also note that Dr. McCary hasn't made many public statements, so it's difficult to deduce precisely what his views are on things. But he did say in a few recent interviews that he does believe, for instance, with respect to rare disease, that relying upon biomarkers and plausible mechanisms of action makes sense. So, on whole, I'm going to remain confident that the FDA is going to be a science-based, evidence-based organization.

Speaker Change: Appears to be quite innovative and her goal of moving.

Speaker Change: Therapies, along and relying upon.

Speaker Change: Modern tools for drug development I would also note that doctor.

Speaker Change: Mercury Hasnt made of many public statements. So it's difficult to do precisely what his views are on things, but he did say and a few recent interviews that.

Speaker Change: He does believe for instance, with respect to rare disease that relying upon biomarkers and plausible mechanisms of action makes sense. So.

Speaker Change: On whole ongoing to remain confident that the FDA is going to be a science based evidenced based organization and hopefully if the interactions that we've had in the last few months or any indication are going to continue to march towards ensuring that Reg.

Doug Ingram: And hopefully, if the interactions that we've had in the last few months are any indication, are going to continue the march towards ensuring that regulatory science can keep pace with actual science and we can begin to really accelerate. You know, to that very end, one of the things that we speak of all of the time is the cost of health care in the United States. And we talk about a lot of concepts. And truthfully, we talk about discounts and rebates and outcome-based agreements, and all of those things are interesting and probably worth discussing. But there is one thing, more than anything else, that from a drug perspective, can reduce the ultimate cost of healthcare in the United States.

Speaker Change: <unk> science can keep pace with actual science and we can begin to really accelerate.

Speaker Change: To that very end one of the things that we speak of all of the time is the cost of health care in the United States.

Speaker Change: And we talk about a lot of concepts in there.

Truthfully, we talk about discounts and rebates in outcome based agreements and all of those things are interesting and probably worth discussing but there is one thing more than anything else that from a drug perspective can reduce the ultimate cost of health care in the United States and that's the ability.

Doug Ingram: And that's the ability to make our therapies, get them through the regulatory process with less unnecessary burden. Stripping down to those things that truly add insight on safety and efficacy, collapsing timelines and reducing the cost and risk of them. If you do that, you can start getting therapies out in the United States and then around the world that will be far less expensive, but equally efficacious and beneficial to patients. So that's the direction in which I see the FDA historically heading, and I'm confident that the FDA will see that that's a brilliant answer for society.

Speaker Change: <unk> to make our therapies.

Speaker Change: Get them through the regulatory process.

Speaker Change: Less unnecessary burden.

Speaker Change: Stripping down to those things that truly add insight on safety and efficacy collapsing timelines and reducing the cost and risk of them. If you do that you can start getting therapies out in the United States and then around the world that would be far less expensive, but equally efficacious and benefit.

Speaker Change: So the patient so.

Speaker Change: That's the that's the direction in which I see the FDA historically heading and I am confident that the FCA will see that that's a brilliant answer for society.

Doug Ingram: Thank you one moment for our next question. Our next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Your line is now open. Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Can you just talk about some of the administrative delays in infusion? I think you mentioned a specific Medi-Cal delay that you said was resolved. Was there something specific driving this? Any information requests from organization or anything like that you could speak about? Thank you. Yeah, that very specific issue, which is the administrative delay, specifically in the first quarter, that was really just an administrative issue.

Speaker Change: Thank you one moment for our next question.

Our next question comes from the line of Christian <unk> of Cantor Fitzgerald. Your line is now open.

Speaker Change: Hi, This is Rick Miller on for Christian Thanks for taking our question can you just talk about some of the administrative delays in infusion I think you mentioned a specific medi Cal delay that you said was resolved was there something specific driving this any information requests from organization or anything like that you could speak about thank you.

Speaker Change: Yes, that's very specific issue, which is the administrative delays specifically in the first quarter that was really just a administrative issue. It was an administrative issue between the sites of care in Los Angeles County Medical the let me give you more detail than you want so.

Doug Ingram: It was an administrative issue between the sites of care in Los Angeles County and Medi-Cal. Let me give you more detail than you want. So normally the thing that decides whether a patient gets dosed is a pre-authorization. So you get a pre-auth. This is not about that. So this is not about patients ultimately getting dosed. This wasn't a fight over access or anything along those lines. This is all about families that already had scheduled infusions and had already gotten prior auths from the payer. So this is not about access or anything. It's a really specific administrative issue, which is, given the cost of these one-time therapies, sites of care often, very, very often, maybe almost universally, are asking of the payers that they sign single case agreements.

Speaker Change: Normally the thing that decides whether or whether a patient gets doses of preauthorization. So you get a you get a pre op. This is not about that so this is not about patients ultimately getting dose. This was in a fight over access or anything along those lines. This is all about families had already had.

Speaker Change: Scheduled infusions and it already gotten prior offs from the payer. So this is not about access or anything it's a really specific administrative issue which is.

Speaker Change: Given the cost of these onetime therapies site.

Speaker Change: Sites of care often.

Speaker Change: Very very often maybe almost universally.

Speaker Change: Are asking of the payers that they sign single case agreements.

Doug Ingram: for that particular infusion, which is sort of a belt and suspension, Spencer's concept of saying I know I'm going to get reimbursed if I do that. And there was this hiccup in the first quarter where there was a delay in those single case agreements. And that caused, you know, people just couldn't get get those. They all got rescheduled, by the way. They all just they all got rescheduled. But outside of the first quarter into the second quarter and then that issue got resolved between the payers and and the state. Yeah. And it does. It's a good question.

Speaker Change: For that particular infusion, which is sort of a belt and suspensor.

Speaker Change: Belt of suspension Spencers concept of saying I know I'm going to get reimbursed if I do this.

Speaker Change: There was a hiccup in.

Speaker Change: In.

Speaker Change: In the first quarter, where there was a delay in those single case agreements.

Speaker Change: And that caused people just couldn't get get dose. They all got rescheduled by the way. They all just they all got rescheduled, but outside of the first quarter into the second quarter.

Speaker Change: And then that issue got resolved between the payers and the state government.

Speaker Change: It does it's a good question and it does really underscore the dynamics of a onetime therapy that.

Doug Ingram: It does really underscore the dynamics of a one time therapy that, you know, if you compare it to our PMO experience, delays in, let's say, 15 patients on the gene therapy in the gene therapy world to get the same kind of financial impact, you'd have to have the delay of 150. It's a tenfold impact for a one time gene therapy versus a chronic therapy. So small, small swings matter. But that works both on the upside and the downside. Yeah, I do want to make sure we're absolutely clear that was purely administrative. It's not an issue we've seen before.

Speaker Change: Compared to our PMO experienced delays in let's say 15 patients on the gene therapy in the gene therapy World. They get the same kind of financial impact you'd have to have the delay of 150, it's a tenfold impact for onetime gene therapy versus a chronic therapy, so small small swings matter, but that where it's both on the upside.

And the downside, but I do want to make sure we're absolutely clear that was purely administrative issue.

Speaker Change: It's not an issue we've seen before.

Doug Ingram: We understand the single case agreement concept well. One of the things you need to know, though, is that we don't participate in the single case agreement. That is between the site and the payer itself. But it's not an access issue. It's an administration. Thank you. One moment for our next question. And our next question comes from Linus Sammy Corwin of William Bayer, the line is now open. Hi, this is Caleb Bowen for Sam and Corwin. Thanks for taking our question. So in regards to patient education, are there particular any particular data sets that families want to want to see before gaining more to gain a little bit more confidence and a little bit following the safety event?

Speaker Change: We understand the single Chase agreement concept well one of the things you need to know, though is that we don't participate in a single case agreement that is it between the site and the payer itself, but its not an access issue. It's an administration issue.

Speaker Change: Okay.

Speaker Change: Thank you one moment for our next question.

Sami: Our next question comes from the line of Sami <unk> of William Blair. Your line is now open.

Speaker Change: Hi, This is scalable infotainment Orlando and thanks for taking my question.

Speaker Change: So in regards to patient education are there particular, any particular datasets are families.

Speaker Change: Want to see before gaining more to gain a little bit more confidence and I love. The following let's say to you that I know you guys presented a lot of safety data, thus far but.

Doug Ingram: I know you guys present a lot of safety data thus far, but Do you, are you hearing anything that families want to see more data and possibly the older non-ambulatory patients to get more confidence there for them? Thanks. Well, I'm going to speculate a bit on, I mean, I think the things that are important to families broadly, so specifically about the safety event, they want to hear about it. What was it exactly? And put it in context. You know, one of the things that families sometimes didn't know is like, is this one of five? Like, have you dosed seven kids?

Speaker Change: Are you hearing anything that they only want to see more data, possibly the older Nonambulatory patients.

Speaker Change: Typically more confidence there for them.

Speaker Change: I am going to speculate a bit on I mean, I think the things that are important to families broadly so specifically about the safety event they want to hear about it.

Speaker Change: Is it exactly and put it in context.

Speaker Change: One of the things that the family sometimes didn't know is like is this one of five seven.

Doug Ingram: Have you dosed 10 kids? No, we've dosed well over 800 kids. That data point's probably becoming stale. We've dosed over 800 kids. So sort of contextualizing it and what that was about and what that meant. The second piece of information I think that's really important to families to contextualize is, you know, do you see anything different here? Is there something about being ambulatory versus non-ambulatory that plays a role in And the answer to that is no. We looked at all the signals. There is no reason to believe that at all. All of the liver enzyme issues are the same across ambulatory or non-ambulatory, Billy Ruhm is the same.

Speaker Change: Seven Q3 dose timken, though we've done well over 800 kids.

Speaker Change: That.

Speaker Change: Data points, probably becoming stale with just over 800 gig sort of contextualize ing it and what the what that was about and what that meant the second piece of information I think that's really important to families to contextualize is do you see anything different here or is there something about being ambulatory versus non ambulatory that plays a role in the answer to that is no.

Speaker Change: They looked at all of the signals. There is no reason to believe that at all the all of the liver enzyme issues are the same across and as our non ambulatory Billy room. The same but then the thing the next big thing that families need to understand is the efficacy they really need to see the efficacy and thats and Thats a lot there's a lot to talk about.

Doug Ingram: But then I think the next big thing that families need to understand is the efficacy. They really need to see the efficacy, and that's a lot. There's a lot to talk about there, right? Because we have a lot of data that supports how beneficial this therapy is. All of the data that supported the original approval, the totality of the evidence was lights out. supportive of it. And then the data that came out, you know, a year later from the original study was just, again, completely lights out. On the two years, kids that are on the therapy for two years were significantly better than natural history on every single measure.

Speaker Change: There right because we have a lot of data that supports how beneficial. This therapy is all of the data that supported the original approval the totality of the.

Speaker Change: Evidence was lights out.

Speaker Change:

Speaker Change: Supportive of it.

Speaker Change: And then the day.

Data that came out a year later from the original study was just again, it's completely lights out.

Speaker Change: On the two years kids that are on the therapy for two years were significantly better than natural history. On every single measure same was true for the older Kids even at one year trajectory analysis was just in a really interesting opportunity where you've got these kids all blinded for two years somewhere around placebo somewhere unfolds drug.

Doug Ingram: Same was true for the older kids. Even at one year, the trajectory analysis was just a really interesting opportunity where you got these kids all blinded for two years. Some were on placebo, some were on full drug. You cross them over at one year. They're all blinded, so they don't know if they had the therapy before or now they're getting the therapy. And what did you see? Kids that had previously gotten the therapy were doing, you know, got a big benefit and then were stable and doing great. They got a placebo. They didn't do anything.

Speaker Change: You crossed them over at one year, they're all blinded. So they don't know if they had the therapy before are now they are getting the therapy and what did you see kids that had previously gone to the therapy, we're doing.

Speaker Change: Got a big benefit in them were stable and doing great. They got placebo. They didn't they didn't do anything they just continue to stay stable. They didn't have a placebo effect, even they just became stable and then the kids they were on placebo when they hit one year and they got this the therapy again, they didn't know they got it.

Doug Ingram: They just continued to stay stable. They didn't have a placebo effect even. They just became stable. And then the kids that were on placebo, when they hit one year and they got the therapy, again, they didn't know they got it. They just rocketed up and did brilliant. You saw this huge gap. So that is really important data for them to see. And then I would argue another thing that they really need to see, because this goes not only to the efficacy of the therapy, but the importance of prioritizing getting this therapy. There's a lot of interesting therapies out there.

Speaker Change: Rocketed up and did brilliant you saw this huge gaps so that is really important data for them to see and then I would argue that another thing that they really need to see because it's because this goes not only to the efficacy of the therapy, but the importance of prioritizing getting this therapy. There's a lot of things you can do for your chip there is interesting.

Doug Ingram: This is a disease modifying. So before you do anything else, you gotta modify the disease. And I would argue the muscle MRI data that they see is really impactful because that doesn't just say that this therapy is important, it says you don't have the luxury of waiting. And I'm not gonna criticize families. I don't know families' personal issues, and why a family might wanna wait till the summer versus getting it in the late winter. But I would argue that if you see the muscle MRI data, you're gonna feel very motivated. I gotta get this kid on this therapy as soon as my family situation would allow it.

Speaker Change: Therapies out there. This is a disease modifying therapy. So before you do anything else you got to modify the disease and I would argue that muscle MRI data that they see is really impactful because that doesn't just say that this therapy is important. It says you don't have the luxury of waiting and I'm not going to criticize families I don't know family.

Speaker Change: <unk>.

Speaker Change: Personal issues and why our family might want to wait until the summer versus getting it in.

Speaker Change: Late winter, but I would argue that if you see the muscle MRI data youre going to feel very motivated I got to get this kid on this therapy as soon as my family situation would allow it because what we saw again is in just one year.

Doug Ingram: Because what we saw, again. just one year. You are not on this therapy. You are going to have a lot more muscle damage that's not coming back. Our therapy doesn't bring the muscle back, and you're going to have a lot more fat and fibrotic tissue that's not going to be helpful. Anyways, I think that sort of whole package of data, and by the way, that's not just for families. This is the kind of information that we really need to share robustly with treating physicians, not only our top treating physicians who get this in spades, but, you know, physicians throughout the countries and referrers around the country so that everybody understands, not only the value of the therapy, but feels the urgency that these kids need to get.

Speaker Change: We're not on this therapy, you're going to have a lot more muscle damage, that's not coming back on.

Speaker Change: Our therapy doesn't bring the Russell back and Youre going to have a lot more fat in fibrotic tissue that is not going to be helpful. Anyway, I think that sort of whole package of data and by the way that's not just for the families. This is the kind of information that we really need to share robustly with treating physicians not only our top treating physicians who get this in spades.

Speaker Change: Physicians throughout the countries and refers around the country. So that everybody understands feels not only the value of this therapy, but feels the urgency that these kids need to get it get infused as soon as an infusion site is available to them in an infusion date is available to them.

Doug Ingram: And you can see some of the tools that we're offering patients now on levidus.com. You can go in and see the various videos, educational tools, including the tools, how we educate them across the treatment journey of what to expect and how to, what to expect and how to manage that treatment journey. Thank you. One moment for our next question. And our next question comes from Landa Uyar of Mizuho. Your line is now open. Hi guys, this is Leo on for OI. Thanks for taking our question. Is there a reason that patients appear to be flocking towards bleeding centers that have full capacity?

Speaker Change: And you can see some of the tools that we're offering patients now on <unk> Dot Com you can go in and see various videos educational tools, including the tools, how we educate them across the treatment journey of what to expect and how to.

Speaker Change: This is <unk>.

Speaker Change: What.

Speaker Change: What to expect and how to manage that treatment journey.

Speaker Change: Thank you one moment for our next question.

Speaker Change: Yeah.

Speaker Change: Our next question comes from the line of <unk> of Mizuho. Your line is now open.

Speaker Change: Hi, guys. This is Leo on for Yi. Thanks for taking our question was there a reason that patients appear to be flocking towards leading centers that have full capacity do you expect any of these leading sites to increase their side capacity and to what extent does your updated guidance account for increased number of infusions at the secondary side figured out targeted.

Doug Ingram: Do you expect any of these bleeding sites to increase their site capacity? And to what extent does your updated guidance account for increased number of infusions at these secondary sites that you're now targeting? So I think it's not at all a surprise that there are so many star forums at the top sites. They are also the top sites. They are, you know, these are the world leading Duchenne sites. Like you could, I don't want to start naming them because I might forget one and then I'll be accidentally insulting somebody. But these are the world's leaders in the treatment of Duchenne muscular dystrophy.

Speaker Change: Thanks.

Speaker Change: So I think it's not at all a surprise that there are so many start forms at the top sites. They are also the top sites.

Speaker Change: These these are the world's leading duchenne sites that you could then I don't want to start naming them because I might forget one and then I'll be I'll be accidentally insulting somebody but these are the these are the world's leaders in the treatment of Duchenne muscular dystrophy. These are the.

Doug Ingram: These are the most renowned sites around the country and frankly around the world. So it should be of no surprise that, you know, a family when they hear about this horrible diagnosis would want to go to one of those sites potentially. And that's why. It's there. So I'm sorry, what was the other part of the question? Listing and so. but Anyways, that's the reason that there was this imbalance. And then I guess on our forward, yes, we're assuming that we're going to get a lot more capacity. We're going to exploit a lot of the capacity in these secondary sites going forward, and that's going to help us.

Speaker Change: Most renowned sites around the country and frankly around the world. So it should be of no surprise that you know.

Speaker Change: Our family when they hear about this horrible diagnosis would want to go to one of those sites potentially and that's why it's it's.

Speaker Change: There, so and I'm sorry, what was the other part of the question.

Speaker Change: Listen it so.

Speaker Change: But.

<unk>.

Speaker Change: Anyways, that's the reason that there was this imbalance and then I guess on a forward. Yes, we are assuming that we're going to get a lot more capacity, we're going to exploit a lot of the capacity and the secondary sites.

Speaker Change: Going forward.

Speaker Change: That's going to help us.

Doug Ingram: not only, hopefully, you know, even get to or even exceed our guidance over the course of the year. And one thing I should remind everybody, all of the sites that are permitted to infuse Sarepta, I mean, Elevitis, are well-trained and validated sites, and they are themselves all brilliant sites. So, you know, there is no reason to believe you're going to get a different quality of care in one of these sites. They're going to all do a great job for you, which you need to focus on. Thank you one moment for our next question. And our next question comes from the line of Andreas Aggeraits of Oppenheimer and Co.

Speaker Change: Not all hopefully even get to or even exceed our guidance.

Speaker Change: Over the course of the year and one thing I should.

Speaker Change: Remind everybody.

Speaker Change: All of the sites that are permitted to infuse <unk> I mean, <unk> are well trained and validated sites and they are themselves. All brilliant side. So you know there is no reason to believe you're going to get a different quality of care in one of these.

Speaker Change: Sites, they're going to all do a great job for you would see the focus on them.

Speaker Change: Thank you our next question.

Speaker Change: And our next question comes from the line of Andreas <unk> of Oppenheimer <unk> Co. Your line is now open.

Ian Estepan: Your line is now open. Good afternoon, and thanks for taking our question. With shares at current levels, how are you guys thinking about the opportunity for implementing the approved buyback? I'll turn this to Ian. As I said in our prepared remarks, obviously, you know, the stock does not, you know, reflect, you know, our guidance still remains $2.3 to $2.6 billion. You know, the stock is trading at levels that aren't even recognizing that. And so we certainly think that it's undervalued, but we've just outlined multiple data readouts, you know, from our pipeline also to, you know, continue to drive growth.

Speaker Change: Good afternoon, and thanks for taking our question.

Speaker Change: Sure.

Speaker Change: Current levels, how are you guys thinking about.

Speaker Change: Opportunity.

Speaker Change: And then can be approved.

Speaker Change: Buybacks. Thanks.

Speaker Change: I'll turn this to Ian.

Speaker Change: Okay.

Speaker Change: As I said in our prepared remarks.

Speaker Change: Obviously, the stock does not reflect.

Speaker Change: Our guidance still remains $2 30 to $2 $6 billion.

Speaker Change: The stock is trading at levels that aren't even recognizing that and so we certainly think that its an undervalued Luis just outlined.

Speaker Change: <unk> data Readouts from our pipeline also to <unk>.

Ian Estepan: So we have to balance, obviously, both our investment in R&D and then our investment in a potential allocation strategy. And that's where we're going to going forward. Obviously, we're not going to be too, you know, direct about about how much we're doing or the like, but it's certainly a consideration that we're looking Thank you. One moment for our next question. Our next question comes from the line of Gena Wang of Barclays. Your line is now open. Hi, this is Tony on for Gena. Thanks for taking our question. So some of our own channel checks have suggested that there are some payers deciding not to cover levitas.

Speaker Change: Continue to drive growth so.

Speaker Change: We have to balance obviously, both our investment in R&D and then our investment in a potential allocation strategy and that's why we went to going forward, obviously, we're not going to be too.

Speaker Change: Direct about about how much we're doing or the like but it's certainly a consideration that we're we're looking at.

Speaker Change: Thank you one moment for our next question.

Speaker Change: Our next question comes from the line of Gena Wang of Barclays. Your line is now open.

Speaker Change: Hi, This is Tony on for Jade. Thanks for taking our question. So some of our own channel checks have suggested that there are some payers deciding not to cover all of it is we were wondering if you could provide any additional color on your experience with the covered so far.

Unknown Executive: We were wondering if you could provide any additional color on your experience with coverage so far.

Louise Rodino: And then second question, when could we potentially expect an update regarding the halt on studies in the Sure. So first on the first one, just be clear and I can use the PMOs as the answer. There are always some subset of payers that resist access and require more work. And it's one of the reasons that cycle times sometimes get extended because you have to go through appeals processes and the like. So there's nothing different about Elevitas and the PMOs, with the exception that probably on a whole, the Elevitas policies are better. So our Elevitas policies on a whole are better, part because we have a traditional approval for a significant percentage of that approval, and in part because we have so much data that supports it.

Speaker Change: And then second question when could we potentially expect an update regarding the halt on studies in the EU.

Speaker Change: Sure. So first on the first one just to be clear I can use the <unk>.

Speaker Change: Answer.

Speaker Change: Always some subset of payers that resist access and require more work in one of the reasons that cycle times, sometimes get extended because you have to go through appeals processes and the like so there's nothing different about <unk>. The PMO hose with the exception that probably on a whole.

Speaker Change: <unk> policies are bad.

Speaker Change: So Paul I'll love it as policies on the or better part because we have a traditional approval for a significant percentage of that approval and in part because we have so much data that supports it.

Doug Ingram: What I will say, and ultimately, regardless of policy, the differences in policies, there's policies to label. There's a lot of them with Elevitas, and I'm really proud of that. There are some policies that try to put some restrictions in, and then there's some policies that are very restrictive. The ultimate answer is an issue for us, but not actually ultimately for the revenue or for you, because we'll get the kids on the therapy in any of those scenarios. Some will take a little longer than others. And that's why I can tell you that with respect to the PMOs.

What I will say and ultimately regardless of policy the differences in policies. There's policies to label, there's a lot of them with a levitous and I'm really proud of that there are some policy. They try to put some restrictions in and then there are some policies that are very restrictive. The ultimate answer is is an issue for us but.

Speaker Change: Not actually ultimately for the revenue for.

Speaker Change: For you because we'll get the kids on the therapy and any of those scenarios some will take a little longer than others and that's why I can tell you that with respect to the Pmo's, we're well over 90% success rate.

Doug Ingram: We're well over 90% success rate in getting those kids on therapy, even when a payer might try to take us to an appeal or something. With Levitas, our current success rate stands at 100. Suggesting that five years from now, we'll still be at exactly 100. But there's no reason to believe we'd be worse than our PMOs, and our PMOs are doing great. So we feel very good about it. And then as relates to the halt, Louise, do you want to chat about that? Sure. Yeah, the EU process requires a need for a substantial amendment. That typical review time is around 95 days.

Speaker Change: And getting those kids on therapy, even win a payer might try to take us to an appeal or something.

Speaker Change: With <unk>, our current success rate stands at 100%.

Speaker Change: Suggesting that five years from now will still be in exactly 100%, but theres no reason to believe we worst in our PMO is in our P&L as we're doing great. So.

Speaker Change: We feel very good about it and then as it relates to the Hall Luis do you want to chat about that.

Speaker Change: Sure Yes.

<unk> process requires the need for a substantial amendment.

Speaker Change: Is that typical review time is around 95 days, so that approval to restart is expected around the end of summer Ah, but just to remind you we are still enrolling outside of.

Louise Rodino: So that approval to restart is expected around the end of summer. But just to remind you, we are still enrolling outside of the EU as well. So the trial continues to enroll and we're on track. Thank you. I'm showing no further questions at this time. I'll now turn it back to Doug Ingram for closing remarks. All right. Well, thank you all for joining us this evening. I will tell you, it's not enjoyable to bring guidance down. It's the first time. Frankly, in my career when I've done it, and I don't intend to do it again, but I do think it was the prudent thing for us to do as we're working through some of these issues, and I feel very confident the team's prepared to work through the issues, and we will achieve our guidance.

Speaker Change: As well the trial container channel and we're on track.

Speaker Change: Thank you I'm showing no further questions at this time I'll now turn it back to Doug Ingram for closing remarks.

Doug Ingram: Alright, well. Thank you all for joining us this evening.

Doug Ingram: I will tell you, it's not enjoyable to bringing guidance down it's the first time frankly.

Doug Ingram: Frankly in my career, when I've done it and I don't intend to do it again.

Doug Ingram: But I do think it was the prudent thing for us to do is we're working through some of these issues and I feel very confident the teams prepared to work through the issues and we will achieve our guidance.

Doug Ingram: You know, I mean, I'm just talking extemporaneously now, you know, I came to, it's more than revenue to me. Okay, it's not about revenue. That's not what upset But revenue is the scorecard for what upsets me. The fact is that I came to Sarepta. just about eight years ago. With a belief that along with some other really dedicated people, we might actually be able to intervene and change the course of a disease that's just horrific for families. And I feel particularly...

Doug Ingram: I'm just talking to Extemporaneously now I came to us so it's more than revenue to me. Okay. It's not about revenue that's not what upsets me.

Doug Ingram: But revenue is the scorecard for what upsets. The fact is that I came to serve up to.

Doug Ingram: Just about eight years ago.

Doug Ingram: With the belief that along with some other really dedicated people, we might actually be able to intervene and change the course of a disease. That's just reflect for families and I feel particularly.

Doug Ingram: for more information visit www.thevenusproject.com It was nothing but a physician that got to tell a family a diagnosis. There's nothing we can do for this boy. So go home and love him and watch him. grow and then die in front of The thought that we might be able to do something about that. was extraordinarily motivated. It's why I came here and why me and 15 other people at Sarepta fight every day for the families that we serve. just a revenue issue for us. This is who we are. And so the very idea that we've gotten to where we've got is impressive.

Doug Ingram: Strong about that right now because I was literally had to go to a funeral yesterday for a young man who.

Doug Ingram: Died of Duchenne muscular dystrophy.

Doug Ingram: As a disease that takes off.

Speaker Change: Awesome really human beings it steals them from their family little ditched by Bitch.

Doug Ingram: No.

Doug Ingram: Almost all of history, it was nothing but nihilism it was nothing but.

Doug Ingram: Physician that got to tell a family of diagnosis Theres nothing we can do for this boy, So go home and love them and watch them.

Doug Ingram: Grow and then die in front of you.

Doug Ingram: And the thought that we might be able to do something about that.

Doug Ingram: As extraordinarily motivated it's why I came here and why me.

Speaker Change: <unk> 15, other people that surround to fight every day for the families that we serve this is not <unk>.

Speaker Change: Just a revenue issue for US. This is who we are and so the very idea that we've gotten to where we've gotten.

Doug Ingram: Okay, we have four approved therapies, we have three PMOs doing a lot of good for kids, and we have a gene therapy that's the best gene therapy, and the most successful gene therapy ever launched. But it's not good enough. I want to be very clear. That's not good enough. All right, because every day when a kid who could have gotten infused does because of an administrative issue, or because of a misinformation issue, or because we didn't get out to the site. That's a day we failed in our mission and we're not going to fail in our mission.

Speaker Change: This is impressive.

Speaker Change: We have four approved therapies, we have three PMO is doing a lot of good for kids and we have a gene therapy as the best gene therapy the.

Speaker Change: The most successful gene therapy ever launched but it's not good enough I want to be very clear that's not good enough alright, because every day when a kid who could have gotten infused does it.

Speaker Change: Because of an administrative issue.

Speaker Change: Because of misinformation issue, because we didn't get out to the site.

Speaker Change: That's a day, we failed in our mission and we're not going to fail on our machine.

So I look forward to updating you over the course of this year. And we've got a lot of other things going on at Sarepta that we're excited to talk to you about later this year. And I thank you all for your support and for your great questions. Thank you for your participation in today's conference. This concludes the program. You may now disconnect.

Speaker Change: So I look forward to updating you over the course of this year and we've got a lot of other things going on a structure that we're excited to talk to you about later this year and I. Thank you all for your support and for your great questions. This evening.

Speaker Change: Thank you for your participation in today's conference. This concludes the program you may now disconnect.

Speaker Change: Yeah.

Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Hum.

Speaker Change: Hum.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: Hum.

Speaker Change: [music].