Good afternoon, and welcome to SREPTA's third quarter 2025 financial results conference call. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Tam Thornton, Director of Investor Relations. Please go ahead.

Thank you, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the third quarter of 2025. The press release and slides are available on the investor section of our website at serefta.com, and our 10-Q will be filed with the Securities and Exchange Commission on Thursday aftermarket. Joining us on the call today are Doug Ingram, Dr. Louise Rodino-Klaypak, Patrick Moss, Ian Estepan, and Ryan Wong. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please refer to slide two on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond disruptive control. Actual results can 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 disruptive 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 obligations to publicly update its forward-looking statements, including any financial projections provided today, based on subsequent events or circumstances. 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 on the investor section of our website. And now I'll turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress.

Thank you, Pam.

Good afternoon, everyone. Thank you for joining us for our third quarter 2025 financial results conference call. Next slide, please. We have much to discuss this evening, but let's begin by reviewing the completion of our confirmatory study for our two ultra-rare disease TMOs, Lyondis and Amondis, before coming back to our quarterly update. Next slide. I'm going to turn the call over to Dr. Reno-Klepak very shortly, but let me first give some broad conclusions. First, we are very proud to have completed our primary confirmatory obligations. Both Amandis and Amandis serve ultra-rare populations with total prevalence, numbering for each no more than about 500 to 800 patients in the United States and an incident rate per year of maybe a few dozen patients. This disease is also heterogeneous and degenerates not over months or years, but literally over decades. These together make the powering and conduct of a placebo-controlled trial particularly challenging. I want to give a huge thanks to our investigators and then very importantly to the brave families who have had the courage to enroll and risk a placebo arm for 22 months. Without this special community that we serve, we would not have completed this unusually onerous study. Second, when reviewing the evidence to support transition from accelerated to traditional approval of a therapy, one, of course, looks to the totality of the evidence. Here, the division recognized the challenges associated with this ultra-rare disease trial and set out a very specific standard for continuing marketing authorizations. As referenced in our Viandas approval material, the FDA gave us a very specific written language about voluntarily withdrawing marketing authorization, which would only occur if, quote, no relevant analyses find sufficient evidence of a clinical benefit. As you will hear from Dr. Rodino Claypack, we believe that we have met that standard and that we have sufficient evidence to discuss with the agency transitioning from accelerated to traditional approval. Consider, as you will see in our press release, the study missed its statistical significance. However, the data demonstrated a consistent and clinically favorable trend across the trial population. Importantly, a portion of this study was conducted over the COVID pandemic period, and as with many studies over that period, the study results were impacted for a variety of reasons. During the pandemic, the rate of missed doses was unusually high, with nearly all patients missing doses and approaching half of whom missed substantial consecutive doses. Participants in the study were also largely shut in and suffered deconditioning and loss of mobility. All of this appears to have confounded results. When one excludes the COVID participants, we see a meaningful treatment benefit, slowing disease progression by about 30%, which Dr. Rodino Clayback will further explain. Likewise, to enroll this study, we were required to admit a broad population from as young as six years old to as old as 13 years old, including those who would clearly have confounding ceiling and floor effects. In a subgroup analysis of those likely to progress, there was a strong statistically significant benefit, and this was across not only the primary, but the other endpoints as well. There is also a wealth of published real-world evidence for the PMOs. As just a few examples of the multiple real-world studies across our PMOs, we see that when trapping biomas over six years, there's an 88% reduction in risk of loss of ambulation with a Kaplan-Meier analysis of delay of about three years. Likewise, with both myondis and amondis, we see over time a significant attenuation in fulminary decline and a significant delay in time to cough assist and ventilation. We see the same trend in our own study essence. As part of the benefits they are seeing, patients are required to be infused weekly, a fairly onerous protocol, and yet their compliance rate has been well over 90% commercially year over year over year. When one considers all of the evidence for benefit and then ways a favorable, stable safety profile is tracked over many years, we believe the risk-benefit remains positive. We not only anticipate continuing marketing authorization, but we believe we have a good argument for traditional approval. Our plan is to schedule a meeting with the division to review the totality of the evidence. Dr. Rudino-Fapak will now discuss those results in more detail.

Thank you, Doug. Can I have the next slide?

Today we announced the top-line results from our ESSENCE trial. The first placebo-controlled Phase III study of exon-skipping therapies, aroundis 53 and amandis 45, across the nation. to treat patients with Duchenne muscular dystrophy amenable to exon 53 or 45 skipping, respectively. To remind you, Vyondis and Amandis are designed to address the underlying cause of Duchenne by restoring the messenger RNA or mRNA reading frame. The therapies use disruptors proprietary PMO chemistry and exon skipping technology to skip exons 53 and 45 of the disrupting gene. Promoting the synthesis of a shortened functional distortion protein is intended to slow decline in Duchenne patients. Biondis and Amandis were approved by FDA via the accelerated approval pathway in 2019 and 2021, respectively.

Next slide, please.

As shown on this slide, initiated in September 2016, the 225-person ESSEN study was designed as a double-blind, placebo-controlled trials spanning 96 weeks, followed by a 48-week open-label extension, reflecting the scale, rigor, and long-term commitment required to validate targeted treatments and select rare disease populations such as Duchenne. The trial was conducted across

75 centers in 24 countries. Next slide, please. In terms of baseline demographics,

patients were well-matched with two-to-one treated versus placebo with numbers of Exxon 45 and exon 53 amenable patients consistent with the prevalent duchenne population functional baseline characteristics were also well matched now turning to the top line results on the next slide essence demonstrated numerical superiority across the primary and most secondary endpoints however the study did not reach statistical significance on the primary endpoint the four step ascend at 96 weeks let me first highlight the key results and then i'll provide more detail on each. First, and as mentioned, we believe COVID impacted study results. A post-hoc analysis of participants not impacted by COVID improved study results on the four-step ascend, with a least square mean difference of 0.11 steps per second and a p-value of 0.09. Second, when a prognostic score is applied to identify the subpopulation at risk for decline on four-step ascend, A meaningful and significant treatment response is evident, with a least-square mean difference of 0.186 steps per second and a p-value of 0.01. And importantly, there were no new safety signals with comparable AE rates between treated and placebo.

AEs were largely mild or moderate. Next slide, please. As you will see on this slide, and as I mentioned previously, although the data showed numerical superiority, the primary endpoint of the study was not met. Next slide, please. As Doug mentioned,

COVID appears to have an impact on study results. The study itself was challenged operationally during the COVID period with twice as many consecutively missed doses during COVID versus COVID-free patients and compressed clinical evaluation schedules. 43% of COVID-impacted patients had consecutively missed doses with an average of eight missed doses. In addition, published studies specifically on the impact of the COVID pandemic in Duchenne have demonstrated a negative impact on function due to immobility, contractures, and increased weight gain. On this slide, I've highlighted the COVID period that falls in the middle of the ESSENCE study, which began in late 2016 and completed in 2025. We defined patients that began

and completed their 96 weeks outside of this window as COVID-free. Next slide, please. Notably, a post hoc analysis of the COVID-free participants

improved study results on the four-step ascend primary endpoint as shown on the left, with a least square mean difference of 0.11 steps per second and a p-value of 0.09. This equates to an approximately 30% reduction in disease progression over two years on the four-step ascend. This is in stark contrast to those individuals impacted by COVID on the right. Had we seen this effect size in a sample size similar for the whole trial population, we would expect it would have reached statistical significance.

Secondary endpoints also demonstrated improved study results in COVID-free participants. Next slide, please. Separately, we also performed an analysis using a prognostic scoring method

published by the well-respected CTAT, or Collaborative Trajectory Analysis Project Group, which was focused on Duchenne. This method, published after we commenced ESSENCE, is used to identify the population most at risk for decline, and consequently, a maximum treatment benefit can be identified by avoiding floor and ceiling effects. The method includes baseline age, four-step ascend velocity, rise from floor velocity, 10-meter walk-run velocity, and corticosteroid duration and type. The four-step ascent was the most sensitive endpoint and reached statistical significance with this prognostic score applied. With a clinically meaningful least-square mean difference of 0.186 steps per second and a p-value of 0.01, this equates to a 35% reduction in disease progression

over two years on the four-step ascent. Next slide, please. There were no new safety signals with comparable adverse event rates between treated and placebo,

reinforcing the favorable and manageable safety profile observed with our exon-skipping therapies. Adverse events were largely mild or moderate. We believe the totality of these data, along with the real-world evidence, are compelling for Amandis and Biondis, and will be sharing these data with FDA to support FNDA filing.

Next slide, please. Of note, and as you will see here, a number of factors generated from the real-world evidence

supports casimersin, including a mean age of 15 years for casimersin-treated patients to meet a wheelchair versus 9.5 to 12.3 years in the literature for standard of care. It also shows a 2.6-year delay in time to reach FBC percent predicted of less than 60% for patients 10 to 18 years old versus match control.

and a 70% reduction in mortality rate for our PMOs. Next slide, please.

On this slide, you will see how the real-world evidence supports Golodersin, including a three-year delay in loss of ambulation versus external control, a 7.5-year delay in the need for nighttime ventilation,

and a 70% reduction in mortality. Next slide, please. As you can appreciate on this slide, the real-world body of evidence supports the effect of our PMOs

on the trajectory of a Duchenne, including an oppressive 5.4-year increase in survival, a three- to four-year delay in loss of angulation, and significantly slower rates of pulmonary

and cardiac decline. Next slide. Further, it's important to note that our exon-skipping therapies have treated over

1,800 patients worldwide, from infants to adults in their 30s, providing a robust foundation of clinical experience and real-world evidence showing PMOs have been associated with slowing Duchenne disease progression, including delayed loss of vangulation, preserved pulmonary and cardiac function, and extending survival. With a patient appearance rate of more than 90%, the sustained use reflects the clinical value of our exonskippers. And we were also pleased to announce at this year's World Muscle Society meeting that a clinically meaningful attenuation of pulmonary decline was demonstrated in patients with advanced Duchenne treated with casimersin compared to matched external controls. And it's also important to note that most of our postmarketing requirements or PMRs

have been completed. Next slide, please. In terms of next steps, with the completion of Essence, we've submitted the top line results

for the agency. We plan to submit a request to schedule a meeting with the Division by the end of the year to review the totality of evidence and discuss the path to a traditional approval. Our findings will also be shared at future scientific forums with plans for publication in a peer-reviewed journal. I'd like to take this moment to thank the Duchenne community, clinical trial investigators, and KOLs for their unwavering support these past years. Drug development often poses what can seem like unmovable obstacles. In the face of those obstacles, particularly in rare and ultra-rare disease, we remain steadfast in the science and focused on taking the best, albeit at times the more challenging path forward for the benefit of patients. We remain committed to our exon-skipping therapies and to the benefit they have provided and continues to provide to those living with insurance. I'll now turn the call back to Doug.

Thank you, Luis. All right, next slide, please. Let's move now to performance. Notwithstanding unprecedented disruptions in the quarter, Elevitus and the PMOs together posted solid net product revenue of $370 million for the quarter. Our chief commercial officer, Patrick Moss, will provide more color on that in a moment. As to the Elevitus label, we have had very productive dialogue with OTP, and we expect the label change process with FDA to be concluded very soon. Dr. Rudino-Klefak will discuss our expectations for the label very shortly, along with our planned trial for the prophylactic treatment of sirolimus. As relates to our portfolio, we are very enthusiastic about our siRNA platform, as the rest of biotech appears also to be ensues with the increasingly the risk potential of siRNA. Luis will discuss our progress on that in a bit. Finally, I would note that in the quarter, we took several important actions to strengthen our financial performance and align our resources with our strategic focus on supporting our current therapies while we advance our largely siRNA-based pipeline. Our CFO, Ryan Wong, will provide color on those actions in his remarks. And with that, I will turn the call back over to Luis again to make some remarks on Elevitus and on our pipeline.

Elise?

Thank you, Doug. Can I have the next slide, please? Moving now to our Elevitus and pipeline updates.

Next slide. To update you on the safety label process for Elevitus, as previously discussed, we've agreed to a black box warning for ALI and ALF. Also, consistent with the action we've already taken to pause shipments to non-ambulatory patients, we've agreed with the FDA that non-ambulatory will be removed from the Indications and Uses section of the prescribing information. Once we have an understanding of the risk-benefit analysis for serolimus, we will discuss with FDA if data are sufficient to resume dosing non-ambulatory patients. Next slide, please. As you're aware, we convened an expert committee to discuss ALF and the potential of adding additional immunosuppression regimens for the non-indulant population. Earlier this month, the committee, which consisted of numerous globally recognized, highly experienced medical specialists, including neuromuscular physicians with elevative treatment experience, hepatologists, and specialist experience in immunosuppressive therapies, shared their findings at WMS, in which they analyzed and reviewed ALF safety data to identify early indicators of ALI and defined populations at elevated risk for ALF. They evaluated and recommended strategies to prevent and mitigate ALI and ALS, emphasizing early risk recognition and patient stratification, a focus on intervention, clinical pathways, and risk-based management, optimized clinical management approaches for ALI and ALS, including prophylactic immunosuppression and monitoring parameters. Based on these discussions and analyses, the committee endorsed modifying hepatic biomarker thresholds in ALI to facilitate timely intervention. They also recommended enhanced liver characterization of baseline to better understand risk factors of developing ALI. In terms of ALI prevention, they recommended adding prophylactic seromas as a second agent to the current corticosteroid regimen versus increasing corticosteroid doses, and this is one to two weeks prior to infusing Elevitus. And in terms of ALI management, the committee recommended prompt initiation of IV corticosteroids if patients do not respond to oral corticosteroids. Lastly, they emphasized the need to generate real-world and clinical data. Before that end, and as we've communicated previously, Cohort 8 of our Endeavor study is designed to demonstrate the effects and myths of additional prophylactic and misuppression in non-ambulatory patients receiving Elevitus. We are in discussions with FDA about the design of the study and hope to be able to commence it soon.

Next slide, please.

Also of note at this year's WMS meeting were the results of an independent study led by Dr. Jonathan Soslow from the Department of Pediatrics at Vanderbilt University Medical Center. The study included 20 Duchenne patients who received a Levitis. The first 14 patients received a Levitis with a standard protocol, including corticosteroids, but no additional image suppression. The six subsequent patients underwent a modified immunosuppression protocol with serolimus. The objective was to show the initial safety, tolerability, and efficacy of serolimus prophylaxis. What the results demonstrated was that a low dose of serolimus prophylaxis appeared to be safe and well-tolerated in the Duchenne patients receiving a levitus,

and there were no observed increases in liver enzymes in the six patients treated with serolimus. Next slide, please. Moving now to our pipeline update. Next slide, and beginning with our LGMD Type 2E program.

Regarding SRP9003 for LGMD Type 2E, we recently presented positive Phase 3 emerging data at the WMS meeting. The study met its primary endpoint, demonstrating a significant increase in beta-circoglycan expression. In addition, restoration of other circoglycan complex proteins in both ambulatory and non-ambulatory patients was demonstrated. Further, our safety and tolerability results were consistent with previous results. We are encouraged by these data to support SRP9003's clinical benefits in patients living with LGMD type 2E. To determine the path forward, we have scheduled a meeting with the FDA this quarter. Following this regulatory dialogue, we will assess the requirements and determine the appropriate next steps for the program. Lastly, we turn to our promising SIRNA pipeline. The recent activity in this space underscores the significant opportunity for this modality, and we are excited by our potential best-in-class approaches. Our GM1 and FSHD programs continue to advance rapidly. Enrollment is progressing well in both trials. For GM1, enrollment in the SAD studies complete, and cohort 4 of the MAD study, a 6 mix per KIG, is currently enrolling. For FSHD, enrollment of the SAD studies complete, and cohort 6 of the MAD study, or 12-mix per kid will begin enrolling this month. While we previously expected to release single dose of sending data by the end of the year, our team is currently prioritizing the transfer and validation of assays necessary to provide high-quality PE data. As a result, we now anticipate sharing these initial results in the first quarter of 2026. We also plan to initiate our trial for Huntington's disease by the year end. This program utilizes the subcutaneous route of administration, allowing for deep brain regions like the Shrierians, particularly affected by Huntington's. In addition to the second-generation DM1 candidate selected at Yale Close, which has the ability to cross the blood-brain barrier and address the cognitive aspects of DM1, we have also selected three of our research targets, which we plan to discuss at a later date. We continue to be excited by our differentiated approaches with SIRNA and look forward to updating you in 2026. I'll turn the call over to Patrick Moss for an update on our commercial performance.

Next slide.

Thank you, Louise, and good afternoon, everyone. My comments today will focus on three areas, a review of our Q3 performance, my thoughts on the Essence results, and our expectations for the trajectory of a Levitus. Next slide, please. Total product revenue for the quarter was $370 million, including $131 million in Elevitus net product revenue, and $239 million in PMO net product revenue. The pause in shipments to the ambulatory population, which resumed following the FDA's recommendation, created meaningful disruptions to patient access. Some infusion dates were canceled, requiring some families to reinitiate the logistical process. antibody testing, rescheduling appointments, and reconfirming insurance authorization. New patient identification efforts were also delayed as a result of physicians requiring clarification on the reasons for the voluntary pause. Despite these challenges, our teams responded swiftly and decisively, working closely with sites and families to ensure continuity of care. Importantly, demand for a levitus proved resilient amongst those patients that had scheduled infusions, with some infusions resuming within a week of lifting the pause on ambulatory shipments. Let's continue to engage our key stakeholders, including payers. We've had productive discussions with payers since the pause and have not seen unfavorable shifts in coverage for Elevitus. In the ambulatory population, approximately 220 million lives have a path to coverage. We continue to fight for our patients, and to date, we're not aware of a single permanent denial for coverage. Our PMO franchise delivered strong demand based on performance this quarter. Performance also benefited from additional shipping days in the Q3 calendar compared to the upcoming fourth quarter. Now turning to the Essence study, we looked forward to connecting with physicians, patients, and payers to share the data at upcoming Congresses and through additional compliant channels. We believe the totality of the evidence demonstrating the value of our PMOs will be viewed by HCPs and families as proof of an innovative treatment option that can have an impact on the trajectory of the disease. Our PMOs have generated a significant amount of real-world evidence supporting the efficacy of these products. The real-world evidence coupled with the data set from Essence only solidifies our view about the importance of these treatment options for patients living with Duchenne. By our Q3 performance, we have successfully restarted shipping for ambulatory patients, and we have begun to see new Elevitus enrollment forms submitted. However, the disruptions in the market this year, combined with the typical seasonal dynamics in Q4, will temporarily impact demand generation and the influx of new enrollment forms. Due to the resulting delays, we expect the Q4 infusion volumes to be flat to slightly down from Q3. Despite these near-term dynamics, we remain confident in the long-term opportunity for Elevitus and are comfortable reiterating our guidance that the ambulant population alone represents an annual revenue opportunity with a $500 million floor. Our conviction is based on the wealth of data demonstrating the benefits of Elevitus. Further, based on our ongoing dialogue with providers, we do not anticipate the inclusion of the box warning in the final labeled have a significant impact on prescribing behaviors, and our field teams are fully equipped to support informed conversations with all stakeholders. The data continues to reinforce this long-term view. We are energized by the reception to our data presentations at this year's World Muscle Society. In particular, the three-year functional outcomes data for Elevitus has resonated strongly with healthcare providers, reinforcing the durability of benefit and the therapy's potential to slow disease progression. Now, to remind everyone, we have now treated greater than 1,100 patients with Alevitis in both the clinical and commercial setting, providing patients with an effective therapy that is designed to impact the trajectory of their disease. Taken together, these results underscore the strength of our portfolio and the resilience of our commercial execution. This team has led an incredible launch through undoubtedly turbulent times, And I have the conviction that this team will continue to deliver results. We remain deeply committed to supporting patients and families, and we are confident in our ability to navigate the near-term dynamics while advancing our mission to transform the lives of those living with this devastating disease. As I continue to meet with HCPs and hear family stories, I am moved by how our therapies are having a positive impact on the lives of patients living with Duchenne. I'll now turn the call over to Ryan Wong to discuss financial results.

Thank you, Patrick, and good afternoon, everyone. This afternoon's press release provided details for the third quarter of 2025 on a GAAP basis as well as a non-GAAP basis. Please refer to the press release available on Threft's website for a full reconciliation of GAAP to non-GAAP financial results. That's my please. I'd like to start my remarks today by thanking this rest of the team for their commitment and diligence as we executed well against the revised strategy and refocused pipeline that we announced in July. Importantly, we took proactive steps in the third quarter to enhance our near-term liquidity and to improve our balance sheet and debt profile. We monetized strategic investments, completed a debt exchange, which reduced maturities due in 2027 from $1.15 billion to $450 million, and significantly reduce our go-forward cost structure. In Q3, we were cash flow positive. Cash flow and investments increased from $850 million to $865 million. And from the Strengthened Financial Foundation, we will continue to advance our pipeline and strategy. I will now touch on the key highlights from our third quarter financial results. Next slide, please. Total revenues were $399 million in the quarter, which consisted of $370 million in net product revenues and $29 million of collaboration and other revenues, which relates to contract manufacturing and royalty income from our partnership with Roche. Q3 cost of sales totaled $151 million, up from $92 million in the same quarter prior year. The increase reflects higher Elevitus cost of goods due to depletion of previously expensed inventory and increased failed batch costs. Additionally, we recorded $22 million in charges for write-off of deposits tied to certain Elevitus manufacturing suites and take or pay shortfall payments. Following the pause in shipping to the non-adventory population, we acted quickly with our strategic manufacturing partner to align Elevitus production with near-term demand. As a result, we have deferred manufacturing commitments and payments from the first half of 2026 to 2027, while maintaining what we expect to be sufficient inventory to meet global demand. Moving on to expenses. Let me start with the restructuring charge reported in Q3. Following our July business and strategy update, which included a reduction in force and reprioritization of our pipeline, we incurred $41 million in restructuring costs, of which $35 million related to severance and other one-time termination benefits, and the remainder related to the accelerated depreciation of certain impacted assets. Moving next to R&D. In the third quarter, GAAP R&D expenses were $219 million and non-GAAP R&D expenses were $207 million, both essentially flat to prior year. Nearly half of our reported R&D expense relates to the $100 million milestone paid to Arrowhead for meeting certain enrollment and safety thresholds in our SRP 1003-CM1 program. Turning to SG&A, we reported $92 million and $77 million on a GAAP and non-GAAP basis, respectively, representing a year-over-year decrease of 28% and 23%, respectively. These decreases were driven by lower compensation expenses as well as lower commercial spend following our cost restructuring efforts. Looking ahead to the remainder of the year, We expect combined non-GAAP R&D and SG&A expenses of approximately $420 to $430 million in the fourth quarter. This includes $200 million payable to Arrowhead for the second DM1 milestone, which we anticipate recording in Q4 with payment due in the first quarter of 2026. For the full year, our guidance for combined non-GAAP R&D and SG&A expenses is approximately $1.86 billion. Excluding the Arrowhead transaction costs and GM1 milestones, together totaling $884 million, our underlying expense guidance is roughly $976 million. Recall, our 2025 guidance prior to our July business and strategy update was between $1.2 and $1.3 billion, which means we have reduced planned expenses by nearly $300 million from the midpoint. This reflects our commitment to discipline capital allocation, and we remain on track to meet our restructuring target into next year. Lastly, in Q3, we reported an operating loss of $103 million and $36 million on a GAAP and a non-GAAP basis, respectively. Adjusting for the $41 million restructuring charge and the $100 million DM1 milestone, our underlying business would have reported a GAAP and non-GAAP operating profit of $37 million and $64 million, respectively. Additionally, adjusting for the $584 million Arrowhead upfront transaction cost, our underlying business has delivered a robust year-to-date gap and non-gap operating profit of $436 million and $561 million, respectively. In closing, with our financial performance and the actions we took in the quarter to strengthen our financial foundation, we believe we are well-positioned to execute our strategy and meet our financial obligations, even under revenue stress test scenarios. Looking ahead, our capital allocation priorities remain focused on investments that drive demand for on-market therapies and advance our SNIA platform for its potential near-term value inflection points. And now I'll turn the call back to Doug for closing remarks. Doug.

Thank you, Ryan. Let's open the call for questions, and then I'll make some closing remarks.

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. We ask that you please limit yourselves to one question to allow everyone an opportunity to ask a question. We'll go first to Anna Pamrama at J.P. Morgan.

Hey, guys. Thanks so much for taking the question.

I had a quick question on Essence. You guys talked a lot about some of the additional analyses and the COVID impact here. What other endpoints should we be looking for in a publication and or medical conference presentation, you know, FDA package that you think that would be supportive of some of the data that you presented here today? Thanks so much.

Yeah, thank you for that question. I will turn this to Luis.

Yeah, thanks for that question.

So, first, we'll be looking at the fatality of evidence. So, essence will be one part of that. But as we mentioned, the real-world evidence data is significant over many, many years and showing a benefit. In terms of essence, this is the top line. We have other secondary endpoints that include functional endpoints and also biological endpoints like expression, which are not complete yet. So all of that will be in the final. CSR will be presented to the agency, and then that will be presented in a medical meeting. But as I mentioned in my remarks, the primary and secondary favored the PMOs, and in terms of COVID, we saw the similar result that we saw with the primary, in which case you saw improvement with those endpoints when you looked at the COVID-free population.

We'll go next to Dean Wang at Barclays.

Thank you for taking my questions. Maybe I'll just follow up. Regarding the COVID-free population, when we look at the p-value, it is still relatively high. It's a 0.09. So, like, how do you think the FDA will look at, you know, the data sets here? And what could be the potential outcome with the FDA decision? You know, one could be for approval. Should we also be worried about the drug could be pulled off the market as a potential worst-case scenario?

Thank you for the question, Gina. I'll make a couple of comments, and then I'll turn it to Luis. First of all, you know, 0.09, I know that the standard is typically 0.05. Interesting enough, FDA leadership very recently noted with respect to rare diseases that 0.05 is relatively arbitrary and actually cited 0.09 as being potentially acceptable p-value. as it says that 91% of the time you're seeing a drug effect, particularly for rare disease. But I would also note that one of the reasons that we're seeing a p-value of 0.09 and we're not seeing a p-value closer to or better than 0.05 is that while 168 patients are included in the analysis here, 57 patients were excluded because their results were affected by the pandemic. And of course, that lowers the powering of this study substantially. So I think in light of the fact that we had to significantly lower the powering of the study to look at 168 versus the additional 57 we would have otherwise seen, I think 0.09 is pretty darn impressive. And the effect, of course, not just the statistical significance of 0.09, but the effect is really important as we were showing a reduction in decline of 30%, which over the long run will be very, very important to these families. And one of the nice things about having these therapies commercially available for so long is that we get to see what happens over the long term, as you saw, with respect to just one example of many, Viondas. You know, you look at that for six years, and these kids are seeing, you know, literally almost three years of delay in being in a wheelchair, and the time to ventilation is significantly different. So I think the outcomes are a couplefold when we talk to the FDA. I really do not believe that there's a risk of losing marketing authorization. It would make very little sense, given both the benefits we've seen with this therapy and considering this extraordinarily beneficial safety profile that we've seen over many years, and when considering the standard that the FDA was very specific with us about as they approved Vyondist in particular, and they were talking to Essence, and they said, the standard is you will be, you will commit to voluntarily withdrawing marketing authorization, but only in a scenario where no relevant analyses would confirm a clinical benefit. And of course, we don't have that between the real world evidence and the evidence we see here. So that, I don't really think that is in the cards in a rational world. And then the real question is, can we transition this therapy from an accelerated approval to a traditional approval? We certainly think we have a good argument around that. We've been spending an enormous amount of time gathering data that supports this, and we think it would be the most efficient approach, but that will require discussions with the agency, and I can't make a prediction on that in advance of having good, solid discussions and review of data with the agency. Now, I said, Luis, I'm going to turn it over to you, and I will do that, but I did go on a bit of a monologue there.

Yeah, I think you covered it well on there.

We'll go next to Tazine Ahmad at Bank of America.

Hi, guys. Good evening. Thanks for taking my question. Mine's on the upcoming Arrowhead data. I wanted to get a sense of what level of data to expect from these early programs that you're looking at. Importantly, these indications, DM1, FSHC, et cetera, are ones that other companies are pursuing. Can you give us a sense of what level of data to expect so that we can potentially start to compare

and contrast with the other programs that are ahead of you in development? Thanks.

I'll turn this to Louise.

Sure.

Well, of course, we'll be sharing data with the single ascending dose study, and we'll be looking at safety, and we'll also have safety data for the multiple ascending dose by that time. So, we'll have PK data, that's serine PK, muscle PK. And then, as I mentioned in my remarks, we are working to validate and transfer the assays, the PD assays. And so that is knockdown for DM1 and looking at splicing. And then for FSHG, we're obviously looking at downstream FSHG gene. So these are assays that we want to validate and have through our pivotal studies. And so we're working hard to make sure that these are in a good place so that when we present our PD data, it can be carried through throughout our studies.

So we're excited to see this result and present it to you early next year.

We'll move next to Brian Abrahams at RBC Capital Markets.

Hi, this is Kevin on for Brian. Thank you for taking our questions. So we just had a couple on the proposed survival in the study. Maybe can you just provide a little bit more color on any key sort of trial design features left to discuss there with the agency, you know, how confident you are in the protocol that you've previously presented, and what, if anything, could be tweaked there, and would you still anticipate a potential readout in the first half of next year for that study? Thank you very much.

Sure. I think, in a general sense, the protocol design will be similar to what we've presented. We haven't finalized it with the agency, but in general, in terms of the numbers of patients and the protocol for serolimus, that hasn't changed. So it's been minor back and forth on the protocol itself. So as soon as we get that study started, we are ready to enroll quickly. Patients are lined up. And so by, as you mentioned, the first half next year, we'll start to have data on the effectiveness. And then in the second half of the year is when we'll have the full data set for the trial based on starting the trial soon.

So we're hoping to get that initiated in the near term.

Our next question comes from Joe Schwartz at LARIC Partners.

Great. Thanks very much. Previously, I think you mentioned that there were around 75 infusion centers around the U.S. that were up and running, although to different degrees. So I was wondering how many are active once again after the pause, and how much variance is there across these centers in terms of the numbers of patients they're treating with Elevitus now? Patrick, you can take this one.

Sure. Well, when we look at the top sites, they continue to treat. Now, those less experienced sites, during the pause, they wanted to understand really the information that caused us to pause. But what we've seen now is the majority of those sites are also starting to submit enrollment forms as well.

We'll go next to Andrew Tsai at Jefferies.

Hey, thanks for taking my questions. I appreciate the updates. So, going back to the PMO franchise, can you remind us when the mission data is for Exxon is 51 and how you would define success or failure in that study, since I believe it's a dose response study, so there's no placebo arm.

Yeah, thank you very much. So, that's a really interesting nuance, and Luis, you're going to correct me. I believe the readout date for mission is 2026. So to your very good point, the mission is a post-marketing commitment that we have with respect to Exondis, but unlike Essence and unlike Viandis and Amondis, it is not a confirmatory study. So there is no confirmatory study for Exondis, and that was purposeful. The FDA in some of their memos indicated that what they really wanted to see was not a confirmation study, but rather a dose-ranging study. So essentially it's dose-ranging between 30 mgs per kg, 100 mgs per kg, even up to 200 mgs per kg. And so the result of that is really a dose. Is 30 mgs per kg the optimal dose, or is 100 mgs per kg the optimal dose? So that's the consequence of that study. It's not a confirmatory study, and that will be that in 2026. and we'll go from there.

We'll take our next question from Salveen Richter at Goldman Sachs.

Thanks for taking our question. This is Tommy on for Salveen. Just wondering about guidance, if there's anything that you can say on full year for Elevitus and about the stress tests that you've done in the past with the 900 million PMO 500 Elevitus. And separately, just on essence, in the context of recent events, we're just wondering of your confidence that the FDA won't move the goalpost here.

I'm sorry, what was the last question? Who the goalposts for?

For essence.

Oh, yeah. I feel confident based on the fact that it was in writing. The standard that we were given was in writing. In fact, we had to commit back to them in writing that that would be the standard. It did not come from a reviewer. It came from, in the first instance, the head of the neurodivision, and then it was cited by the supervisor for over-neuro. So I think this was a very well-established standard that we have. Plus, you know, the fact is that these therapies have been on the market for a number of years. We have extraordinary real-world evidence on their use. As I think we mentioned before, this is one of the most, you know, onerous uh protocols for a therapy you could imagine for commercial therapy these young men and boys um have to be infused on a weekly basis and yet families in recognition of the benefits they're seeing um are um have a compliance rate year over year over year that's greater than 90 percent um commercially and the safety profile for these therapies is you know just is exceptional i think would be the fair way to say it so you know i i don't imagine that there'd be any reason why the division would want to change its standard, it would seem to be unnecessary. As we release the guidance, we're not in a place to give broad guidance right now, but we feel on the stress test concept, we continue to feel comfortable on that stress test we talked about. That is not our guidance for next year. We're going to come together on that. I'm looking at Patrick when I say that, but we certainly feel very comfortable about that kind of baseline concept of $500 million for Elevitus. Anything else you want to say about that for the rest of the year, Patrick? Nothing new to add. Thank you.

We'll go next to Gil Bloom at Needham & Company.

Good afternoon, and thanks for taking our question. So when should we expect to receive

data from – expression data from patients receiving prophylactic

serolimus. And would any be provided from the ISD that was conducted separately? Thank you.

Louise? The expression data would – assuming the

study started soon would be late next year, just in terms of obtaining the biopsies and analyzing them. In the study that Dr. Soslop conducted, the biopsies were not part of that. I think that is something that he's looking at, but that was not part of the original study design.

I think that is a very good question and a very interesting one. You know, the primary reason that we're looking at the use of prophylactic sirolimus is the evidence we have preclinically and some of the early clinical data that it will greatly enhance the safety profile of this therapy, particularly for non-andulatory patients. But one of the things we've seen preclinical, we have not seen clinically yet, because no one's performed a biopsy yet. Preclinically, we've seen the opportunity to potentially greatly enhance expression, which in turn may significantly enhance benefit and durability and the like. So we're very interested in seeing, in addition to the safety issue, which is without a doubt the primary reason we're conducting this study, seeing some of that expression data as well, but that will be in next year.

Next, we'll go to Yan and Xu at Wells Fargo.

Great. Thanks for taking our questions.

Just maybe a quick follow-up to a prior question. To what degree does FDA's reaction to Essence spill over, for example, to Exandes 51? Is there a possibility that the decision or reaction, positive or negative, is there a mechanism for it to also apply to 51, because there's no formal 51 confirmatory studies. And also wanted to, curious, in your mind, what is the relevance of the precedent of NS Pharma, you know, their faith confirmatory trial, and that outcome, whether that has any implication to your situation? Thank you.

I think the only thing I'd say about NSPharma, and we don't know a ton about the details other than I think it is certainly proof that this division is being rational and isn't being excessively punitive for those who may not know. NSPharma had a study for a PMO. That study did not hit STAT-SIG. I think there were some reasons for that. I think the division's been quite thoughtful about that. And that happened some time ago, and they certainly don't seem to be moving to do anything irrational. To your first question, the question is an interesting one, do you think the outcome of essence has some read through in some way to Xandis? And the short answer is no, it doesn't, either positive or negative. I don't think it gives us a great mechanism to immediately make Xandis traditional approval if we're able to get the traditional approval for Viondus and Amondus, and likewise, I don't think it has any other negative read-through to Xandus at all for the simple reason that Essence is specifically for two therapies, Viondus and Amondus, that, you know, we're in that study, and Xandus doesn't have that kind of study. Again, Xandus was approved with a post-marketing commitment to look at dose ranging. We'll have an opportunity to talk about transitioning to a traditional approval with expand us, but only after we've completed our post-marketing commitment to look at that dose ranging study of the 3,100 and even up to 200, and then look at the, you know, the benefits of that versus, you know, the downsides of, you know, extra dosing and the time that it takes to infuse. So we'll look at all of that, and that'll be its pathway to a traditional approval if things go

well there, but the essence doesn't ever read through there as far as we can see logically.

We'll move next to Mike Olds at Morgan Stanley.

Good afternoon. Thanks for taking the question. Maybe just to follow up on Essence in terms of timelines here, you know,

when could you potentially meet with the FDA and when would you expect to roughly have a final decision on that, on the PMO franchise?

Louise, do you want to take that?

Sure. So the meeting request will go in by the end of the year. So the meeting will take place sometime in the first quarter based on that request. And so then later in the spring, the final CSR will be submitted, and then the outcome of the meeting with the agency will determine next steps.

So we'll update when we have something new to share, but the meeting will happen in the first quarter of the year. We'll go next to Brian Scorny at Baird.

Hey, good afternoon. Thank you for taking the question. I guess, you know, the study's been running for 10 years now, and the original design was six-minute walk, and I don't think it was changed to this four-step ascend velocity until under a year ago, and prior to that, it wasn't flagged as, like, a secondary endpoint. So, I guess, with switching the endpoint and mistake, what does the six-minute walk data look like, and what was the rationale last year for changing the analysis?

Louise, do you want to take this?

Sure. Yeah, so we evaluated the endpoints following our 11th Embark data, and so we did an analysis of endpoints and engaged external trail wells to help us do that, moving to an endpoint that was perhaps more sensitive in this. And based on the data, we – picking the forced air climb versus the six-minute walk test was the right decision in terms of it was determined to be the most sensitive end point in our hierarchy. And I think the additional analyses we did from both a COVID perspective and a prognostic scoring method also showed that when you applied those thresholds, we see that the – in terms of COVID, we see almost reached significance. And then when we did with prognostic scoring method, we did see that we reached significance.

So it was certainly the right end point for the study. We'll go next to Ritu Barl at TD Cowan.

Good afternoon, guys. Thanks for taking the question. I wanted to dig in a little further on the dynamics that will drive the down quarter next quarter. Can you elaborate on, I guess, the changes in shipment? I mean, is this sort of a lag on the delay that the disruption or the shipping disruption caused, or is it something more fundamental? And sort of wrapped in all of this is how is safety monitoring around ALIs changing for the ambulatory patients? Are you finding that clinicians are sort of adopting these new monitoring suggestions that were detailed in World Muscle for ambulatory patients, and is that slowing things down?

Yeah, I'm going to turn this over to Patrick. I mean, let me say in the broadest of stroke, it is the downstream pale that occurs when you have this massive disruption. I know people were a bit surprised that we were resistant to this temporary pause. But you can see the impact. We had a temporary cause for a very short period of time, but that really creates a significant downstream disruption. We've said many times the process to go from start form to infusion can be four to six months. So there's just a resonating impact when you have just a complete pause and then you have to restart everything. But, Patrick, you can provide more nuance than I can on this.

Absolutely. And I'll add, in addition to what Doug just shared, we have really three dynamics this quarter. One, the medical conferences to where many of our ACPs are out of their offices for many days, you know, weeks at a time. We've got also the major holidays that are going to impact infusions. And then the third is the inevitable illnesses that can pop up this time of year. So all that comes together, and it's what we've seen last year as well could impact this quarter's infusions. And so that's why we're projecting this quarter to be flat to possibly down in the fourth quarter.

We'll go next to David Wayne at Deutsche Bank.

Hi, thanks for taking my question. So I guess maybe following up on some of the Elevitus dynamics that we already asked about, are you at a place where you can kind of provide a little bit of color on when you think Elevitus demand would be normalized and we might see an inflection in revenues? And then as you think about some of the other competitor gene therapy products out there, one of which I think is seeking accelerated approval, you know, sometime next year, Does that factor into kind of how you think about how Elevitus demand may play out?

I'm not going to comment on nor editorialize on other people's claims with their drugs. But as relates to commercial performance, Patrick, perhaps you want to provide some commentary on that?

Yeah, and the early view is that, you know, based on our commercial execution and the trends that we're seeing, It does support that floor that we talked about. You know, as we get further into this quarter, we'll also, you know, see additional demands and additional enrollment forms come in, and, you know, we'll be able to give an update

at a later time, more likely the J.P. Morgan timeframe.

Next, we'll go to Mitchell Kapoor at H.C. Wainwright.

Hi. Thanks for taking our questions. This is Jade on from Mitchell. So, you stated today that the majority of previous Elevitus cancellations were reordered, but can you provide the actual hard numbers on the infusion postponements versus the number of cancellations you've gotten? And do you have like an actual number of start forms that have been filed for this third quarter?

Yeah, we're going to use revenue as our metrics, so we're not going to provide that level of detail. If you have anything to say, Patrick, about the canceled doses, you can certainly touch on that.

Yeah, so during the pause, we had 14 cancellations, and we have seen 11 of those patients reschedule and were redosed within the August timeframe,

and the remainder are still working through the system.

Next, we'll go to Barron Amen at Piper Sandler.

Yeah. Hi, guys. Thanks for taking my questions. I had a question on Essence. If patients missed doses due to COVID, then you should expect dystrophin production on Western blot and percentage of dystrophin-positive fibers to also be impacted between COVID and non-COVID patients. However, you know, there was an analysis that I think the company presented interim data on at the World Muscle Meeting October 2022 at week 48, that analysis showed no impact for 43 patients that were randomized to either Mondus or placebo on exon-skip and dystrophin production, dystrophin-positive fibers, dystrophin intensity. Each of these endpoints were P-value step six. So I just want to kind of understand how do you correlate that internal Mondus data on these biomarkers to the final functional data where you did see a COVID impact.

Lisa, do you have a comment on that?

Yeah, a couple of points on that. So, we'll – once we have all of the final data, we can certainly do a sensitivity analysis to look at this. I think one thing to remember is that the patients didn't have – there's not a single patient that had biopsies at each time point, so it's difficult to track. So all patients had baseline biopsies, and then the subset had them at 48 and another at 96. And so once we have all of the data, we can go back and look for sensitivity to see if there was an impact on dystrophin expression. But it is complicated by the fact that not every – that patients didn't have sequential biopsies in the study in terms of 48 and 96 weeks.

They were separate patients. We'll go next to Gavin Clark-Gardner at Evercore.

Hey, guys. I just wanted to follow up on the Elevitus trajectory question. So acknowledging there could be a four- to six-month lag, as you noted, have you seen a pickup in start forms over the last one to two months that gives you confidence there will be a notable revenue pickup in 2026? Pratchett?

We're starting to see sites, identify patients, and send in their enrollment form. Every patient has a very distinct journey that they have to go through. So it's the antibody screening and the testing and their pre-screening before they even start the authorization process. And so the early trends are supporting the, you know, the positive outlook.

And as we get more data, we'll share at a later time.

Our next question comes from Yajal Yolko-Movitz at Citi.

Hi, this is Juan Kim on three years old. Thanks for taking our question. Maybe just two quick ones from us. Regarding Alevitis, can you speak on whether you're currently seeing prescribers use serolimus prophylactically for ambulatory patients? And for non-AM patients, can you remind us of the latest thinking around balancing the potential higher risk of infections in using serolimus, and if there was any discussion amongst KOLs or the FDA to not utilize serolimus prophylactically in all non-AM patients given this risk? Thank you.

All right. With respect to the latter question on the non-endritory, that'll be the outcome of our study. We feel pretty confident going into it that the risk-benefit is going to justify the prophylactic use of sirolimus, but we'll only know that when the study reads out, and we'll look at those issues versus potential issues associated with, you know, risk of infection. I will say that to your first question, we don't have a systematic look at what physicians might be using prophylactic sirolimus. We definitely have anecdotal evidence that a significant number, particularly more sophisticated physicians, have used it. And what we're hearing, at least anecdotally, is that they're not having a lot of problems with the use of sirolimus prophylactically. So what we've at least heard anecdotally is that some are using it, and they are finding it very manageable, and I think they find a benefit from it. But this all has to be confirmed, and we have a study that we're going to start when we get to go ahead with the FDA, which hopefully, again, will be very soon. And then we'll be off, and then we'll get the data back, and we'll get to review it. And if we are confident that it's going to change the risk-benefit, we certainly have a lot of conviction that it could.

then we're going to talk to the FDA and start dosing on ambulatory patients again.

We'll go next to Sammy Corwin at William Blair.

Good afternoon. Thanks for taking my questions. Given the turnover at FDA, you know, I understand that you had written guidance previously from the head of neuro, but I guess when was the last time you interacted with a division regarding the ESSENCE trial? And then just curious, the percent of patients that missed consecutive doses in the ESSENCE trial that were in the non-COVID group. Thank you.

As relates to that second issue, on the consecutive doses, I think it's more than doubled or around doubled in the COVID period versus the COVID-free period. We haven't, you know, we haven't had any specific discussions other than administrative-related discussions with the agency regarding Essence over, you know, the last bit of time, certainly not in the last six months, I don't believe, unless the police corrects me. But, again, I think we're working with the, you know, I know you see, you know, without editorial lines, you see all this sort of turmoil at the FDA leadership level recently over the last few days. But I think at the division level, that's where this decision is going to be made. And I'm confident that the professionals in that division are going to take a careful look at this. And I think we are going to be in good shape with respect to marketing authorization. And I'm hopeful that we'll actually be in good shape when we talk to them about transitioning from accelerated approval to traditional approval.

Next, we'll go to Kristen Kluska at Cantor Fitzgerald.

Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Just one here. To follow up on the MISSION trial, you said good readout next year for Exondis. Do you have any insight on how the FDA might look at any of these dose-ranging data you could generate there? Would you plan to meet with the agency after that trial? and just any insight you can give on what that conversation might look like?

Yeah, and I think it's going to look at the totality of the evidence from that study and just ask the question, is there a benefit to these patients by increasing the dose, perhaps to 100 mg per kg versus to 30 mg per kg? And, you know, it's going to be a totality of that evidence about whether that occurs or not. On the one hand, there might be a benefit. We might see some benefit either functionally or in expression. On the other hand, you know, it has to rise to a certain bar because we are seeing a benefit from a trondus at 30 minutes per keg, and that already takes nearly an hour a week. And if you start increasing the dose to 100, surely 200 is probably not actually viable for these patients. The amount of time that you're infusing these kids is enormous, and the imposition is extraordinary. So that's the whole thing we're going to have to look at And then together decide if, you know, I mean, the good news is we're going to be completely aligned in our view of the agency and us. If 100 mix per kid was superior to 30 mix per kid for these kids and the risk benefit and the administrative issues justified it, we'd be fine doing that. But we need to look at that data very carefully. So, again, the mission is not a confirmatory study. The result of mission will either be we're going to be continuing to distribute Exondus at 30 mix per kg or we're going to be distributing Exondus at some dose higher than 30 mix per kg.

If it was higher, it would very likely be 100 mix per kg.

And next we'll go to Annie Chen at Wolf Research.

Thank you for taking the question. This is Brandon on for Andy. Regarding your floor assumptions on elevated fails, to what degree are you factoring competitive pressures from emerging therapies?

We've considered emerging therapies. Again, this is just a stress test. It's not our guidance.

It's just, you know, this is a number that we would be very comfortable. We'd be in fine financial shape. we'd be able to maintain our revolver and lay our debts and advance all of our programs.

So we're feeling very comfortable about that as a floor.

And that concludes our Q&A session.

I will now turn the conference back over to Doug for closing remarks.

Well, thank you all very much for spending some time with us this evening. We all look forward to continuing to update you as we get through the rest of this year and we'll have some additional milestones. And as we look forward into next year, we'll provide updated guidance next year, of course. And then we're really excited early next year to provide you an update on the actual clinical data from our SIRMA programs. That's enormously important to us. So with that, have a lovely evening.

And this concludes today's conference call. Thank you for your participation. You may now disconnect.