Good day, and thank you for standing by. Welcome to the Sarepta Therapeutics Update Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your speaker today, Doug Ingram, President and CEO. Thank you, Josh. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics call to review the top-line results for EMBARK, our double-blind, placebo-controlled study intended to confirm the benefits of ELEVIDYS in children with Duchenne. Next slide, please. We will very likely make some predictions about the future or other forward-looking statements this evening. I would ask you to please review our public filings for the various risks and uncertainties that come with those sorts of forward-looking statements. Next slide. In a moment, Dr. Rodino-Klapac will review the results and our path forward, but let me summarize at least our perspective on them now. Our perspective is that the EMBARK results have met the standard for substantial evidence of effectiveness, confirming the mechanism of action of ELEVIDYS and showing that it alters the course of disease in Duchenne patients. The evidence is also clear that ELEVIDYS benefits Duchenne patients across the ages studied, and there are no new safety signals that have emerged confirming the laudable profile upon which ELEVIDYS was approved in June. Importantly, we have already shared the top-line EMBARK results with FDA leadership and have had encouraging early discussions with them. On that basis, we are pursuing an application to expand the label of ELEVIDYS, and they have confirmed they are open to evaluating an application to expand the label. Our goal is to expand the label to cover all amenable Duchenne patients without regard to age or ambulatory status. FDA leadership has also confirmed their goal of moving swiftly to review this new data and conclude its review on the label expansion. Hence, we will be moving rapidly to make a formal submission, even as the FDA already has our top line to commence its evaluation now. With that, let me turn the call to Dr. Rodino-Klapac, who will lead us through the top-line data. Louise? Thank you, Doug. I am very pleased to share the results of our PMR study, EMBARK. The data strongly supports the conclusion that ELEVIDYS demonstrates a treatment benefit that is clinically meaningful and similar regardless of age. Next slide, please. I'd like to briefly remind you of the EMBARK study design. Next slide. EMBARK is a phase III double-blind, randomized controlled trial with one-to-one randomization with 125 patients enrolled. Crossover occurs at 52 weeks, maintaining the blind to both the study team and the patients. Biopsies are at 12 weeks in a subset of patients for an N of 31 of the 125 enrolled. The primary endpoint is change in NSAA from baseline to week 52. Key secondary endpoints are SRP-9001 dystrophin protein expression, time to rise, and 10-meter walk-run. Three other secondary endpoints were also timed performance test. The SV95c, which was measured using a wearable device, the 100-meter walk test, and the ascending 4- stairs test. There were no dropouts of the study. Next slide, please. This slide demonstrates that the treated and placebo group demographics were very well matched at baseline. Next slide, please. Similarly, on this slide, treated and placebo group functional abilities were well matched at baseline. As you will recall, our stratification factors for this study were age and baseline NSAA, and you can see the groups were well balanced at baseline. Next slide, please. I will now review the EMBARK top-line results. Next slide, please. While it's not on the slide, I'd like to note that, as expected, ELEVIDYS protein expression was highly significant at P is less than 0.0001, as the first key secondary endpoint. We look forward to presenting the full data set at a future medical meeting. Today, I will focus on the functional endpoints. So first, I'm showing you this forest plot, and I'm going to allow you to digest it for just one minute. I'm sure you can see the compelling data that we see. All endpoints favor ELEVIDYS. We acknowledge that the primary endpoint of NSAA at 52 weeks did not reach statistical significance, although it favored ELEVIDYS, and I'll discuss this in more detail. However, there was a robust and clinically meaningful treatment benefit demonstrated across the secondary endpoints of physical function. All three key secondary endpoints strongly reached statistical significance, and all other secondary endpoints favored ELEVIDYS. The consistency demonstrated across these objective measures is strongly supportive of a treatment effect that it was simply not detected by the NSAA score at this 52 week time point. Next slide, please. Now let's look at the forest plots broken out by age subgroup. The mechanism of action and totality of evidence supports a treatment effect that is independent of age across the breadth of the secondary endpoint. Even though we did not power the age subgroups, they were strongly significant for the key secondaries for each subgroup. In addition, there was consistency across all the secondary outcomes. We note the inconsistency in the NSAA results for the six to seven-year-olds, which was not present in the performance on the timed function test. Next slide, please. Now I will show you each of the key secondary measures individually, starting with time to rise. On this slide, we see the time to rise by visit, where the values are least square means plus or minus standard error. The treated groups in purple demonstrate stability or improvement in their times to rise. In contrast, the placebo patients in gold demonstrate increasing time to perform this skill in both age groups. We see significance in not only the overall population, with P equal to 0.0025, but also in each of the age subgroups. Next slide, please. Now for the 10-meter walk- run. Similar to the previous slide, the treated patients in purple demonstrate stability or improvement in performance, while the placebo patients in gold demonstrate more modest improvement or worsening in their function. Again, both the overall population and age subgroups are significant. Next slide, please. Here we see the NSAA by visit, with increasing scores indicating improved performance. As expected, ELEVIDYS treated groups were stable or improved. However, despite the decline in performance evident on the timed function test, the placebo group in gold showed stable to improved NSAA scores. This incongruity is particularly evident in the six to seven-year-olds and suggests the NSAA scores are masking meaningful decline that the time tests are able to detect. Thus, we were unable to detect a significant difference at 52 weeks. We expect we would detect a difference over a longer time period. Next slide, please. I'll now talk about the safety profile. Next slide. Regarding safety, importantly, no new safety signals were identified, with a profile consistent with our previous studies. Benefit risk is favorable and strengthened by this additional data from EMBARK. Next slide. Now I'd like to discuss the clinical significance of these results. Next slide. Timed tests are responsive to disease change, and time to rise was intentionally selected as the first functional key secondary endpoint. The timed function tests are lost sequentially as DMD progresses. We know both from the existing literature and an analysis of our own clinical data preceding 301, that lengthening time to rise is the earliest sign of disease progression and the clearest marker of decline in the four to seven-year-old population. Lengthening time to rise is classically followed by increasing times in the 4-stair climb and then the 10-meter walk-run. The selection of time to rise and 10-meter walk-run as key secondary endpoints in the 301 trial reflects the responsiveness to disease change in this population, as demonstrated by natural history data. Time to rise, `4-stair climb, 10-meter walk- run, and 100-meter run are all accepted registrational endpoints by global regulators and are primary outcomes in a number of contemporary DMD trials. Next slide. I'd like to take a minute to pause here. This slide is important to understand, as I will describe. The strong prognostic power of time to rise and the particular importance of the five-second milestone is clearly demonstrated in this recently published natural history study, drawn largely from the U.K. North Star Network. Here, patients are grouped by their baseline time to rise and then followed over time until they lose ambulation. Patients with a time to rise of greater than five seconds at baseline are seen to have a subsequently aggressive disease trajectory with early loss of ambulation. A rise time of less than five seconds was an inclusion criteria in our trial. We made this decision based on observations from our 9001-102 study, where a number of patients with a baseline of greater than five seconds deteriorated rapidly on the NSAA, irrespective of treatment. While we still believe patients can gain benefit from treatment, we concluded that their exclusion would create a more homogeneous population for investigation over one year. Next slide, please. Understanding that all patients in EMBARK started with a time to rise of under five seconds, we looked at the impact of ELEVIDYS treatment of preventing progress to this important disease milestone. As you can see from this table, treatment with ELEVIDYS reduced the odds of progressing to a rise time of greater than five seconds by 91%, a hugely clinically meaningful treatment effect, driven, as you might expect, by the population more likely to decline, the six to seven-year-olds. Next slide, please. I'll next talk about our path forward and summarize. Next slide. As we have communicated, we are moving with urgency to provide these results to FDA as a BLA supplement to seek label expansion. We have provided this top-line summary of the results to FDA and have engaged in productive and encouraging conversations with CBER on the data. In terms of next steps, we plan to submit an efficacy supplement to CBER as soon as possible, seeking label expansion to treat all DMD patients, and we'll submit a post-marketing requirement, or PMR, seeking transition from accelerated approval to traditional approval. Next slide. To summarize, the data from EMBARK exceeded thresholds for substantial evidence of effectiveness, and the risk-benefit of ELEVIDYS remains favorable. We are pleased with the consistency, the magnitude of response, and the clinical meaningfulness of the results from EMBARK and from the body of evidence supporting ELEVIDYS. The data show ELEVIDYS is a disease-modifying therapy, and therefore, we believe all patients with Duchenne can benefit from treatment with ELEVIDYS. Following positive discussions with FDA leadership, they are committed to evaluating a labeling expansion to the full extent possible based on a review of the data and will do so rapidly. I will now turn the call back over to Doug to open up for Q&A. Well, thank you very much, Dr. Rodino-Klapac. Before I open up the call for Q&A, I would remind everyone that we have an earnings call on Wednesday, and we'll talk about quarterly performance and any other issues there. So with respect, it would be great if people would limit their questions to this data and the EMBARK readout and our path forward. And with that, Josh, let's open up the call for questions. Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. One moment for questions. Our first question comes from Brian Abrahams with RBC Capital Markets. You may proceed. Hi, good afternoon. Thanks for taking my questions. I guess first, I'm wondering if you saw any predictors of better or worse response here. I noticed that in the baseline characteristics, you had more patients with large genetic mutations in the ELEVIDYS arm. And then secondarily, can you talk about the biopsy results here relative to the prior studies? Did the biopsy data here support the potential for dystrophin expression to predict function across all age ranges? And to what degree has the FDA indicated that this would be important for confirmatory evidence to support full approval? Thanks. Great. I'm going to turn both of these questions over to Louise, but just to remind, Brian, the biopsy results we have right now are a small subset in EMBARK, given that we did only a small sampling, we have to get the Part Two as well. But as Louise said, not only were they strongly statistically significant and very robust, they're in the range of what we've seen previously, so it's all very consistent. But with that, Louise, perhaps you can answer both of those two questions better than I could. Sure. Just starting with the first question about any predictors, looking at mutations. So far, just looking at the baseline characteristics, they're well matched. We didn't see any things like mutation leading to prediction of the responses that we saw. With that said, the team is continuing to work on the data. This is the top-line data, and the team is continuing to do analysis, but nothing so far. The data was very clear, and we were very pleased with the execution of the study and how well matched the two arms were at baseline. With regards to expression, as Doug mentioned, this was a subset of the biopsies. The expression data was consistent with what we've seen. Global regulators did not want us to biopsy every single patient, so there was a subset in the Part One as well as a subset in Part Two, and we will share this data at a future medical meeting, along with the entire data set for the study. One final thing to note is the lack of something. You asked about any, any better or worse. Remember, the significant open question in EMBARK was whether this therapy would work better, for instance, in the four to fives than in older patients, in this case, the six to sevens. And what we were, you know, very pleased with is that consistent with prior data and our hypothesis, there was no difference. And in fact, while we had not powered the key secondary endpoints for statistical significance in the subgroup analyses by age, as Dr. Rodino-Klapac noted in her presentation, we saw them strongly statistically significant in both of the age groups, in both of the key secondaries, and almost identical in their statistical significance and in the clinical meaningfulness of both of those results. So it's very, very comforting that this therapy is working well across the ages, and as one would expect, it will, from our perspective, work across all of the ages into non-ambulatory as well. Thank you. One moment for questions. Our next question comes from Tazeen Ahmad with Bank of America. You may proceed. Hi, good evening. Thanks for taking my questions. Doug, is there any way you can provide any color about the specifics of the conversation you had with FDA as it relates to the four to five -year-olds? Did the topic of whether the data that you've collected thus far meet the criteria, at least for the four to five -year-olds, to have, permanent approval for the market? And then secondly, j ust wanted to ask you, what in that conversation did you find encouraging, to give you the view that, that a broad label here is something that the FDA is seriously going to consider? Thanks. Yes, thank you very much for your questions, Tazeen. Let me—I'm gonna answer these very broadly, of course. First of all, the meetings we had were with, as we've said, senior representatives for the FDA, including but not limited to the Center Director, Dr. Peter Marks. We were not discussing whether we meet the standard for the fours and fives staying on. I think that is an obvious win on that issue. What we were really discussing was looking at the totality of this evidence, the ability to expand this label, and from our perspective, to expand it by removing artificial age limitations and removing the artificial restriction to ambulation, as we don't think that's consistent with the mechanism of action or the data. I would broadly say, without going into a lot of detail, I would say everything about that meeting was encouraging. It was a very productive, very positive meeting. I wanna be very clear, you know, we still have a submission to have and a review to go through, but I was very encouraged by the discussions with the agency. They were very clear that they are very committed to moving rapidly, and they were very clear that they are very open to reviewing this application to look to expand the label, of course, you know, supported by a full review. It was a very, very encouraging meeting. Okay, thanks. Thank you. One moment for questions. Our next question comes from Gena Wang with Barclays. You may proceed. Thank you. I'll just follow Tazeen's question. How soon will the FDA get back to you regarding the next step? And also, what was the FDA feedback regarding if we look at the slide 14? You do have the North Star, we do see like six to seven- year-olds, the P value is 0.9378. You know, any comments on that? I think everything else looks like very consistent. Only this one we saw, not much inspiration there. And then also, what is the FDA comment on two-year studies? Is there any way you can conduct two-year study to prove the longer follow-up, you can see the North Star, a further separation? There's a lot in there to unpack, Gena. First of all, to be clear, there was no discussion about additional studies necessary, nor do we envision that there would be the need. Again, without assuming in advance that they fully accept the exact analysis, I think everyone was tracking to the analysis of this data. I'm gonna kind of going backwards in your questioning. What that means is look... Yes, very good. I'm glad you raised that. If you look at the six to seven-year-olds, you don't see separation between the treated children and the untreated children as relates to NSAA. Then interestingly enough, if you look at the time to rise, the much more objective, it turns out, with the benefit of hindsight, time test, or you look at the 10-meter walk-run, again, a very objective time test. You see that in the six to seven -year-olds, the treated kids are stable, which remember, is that long-term therapeutic goal here. In fact, that is a massive win. And when you look at the secondary endpoints, what you see is that the untreated kids are unfortunately becoming much slower, both on time to rise and on the 10-meter walk-run. And I would also notice that's the same answer for the 4-stair climb. It's the same answer for the wearable as well, the SV95. And then look at the NSAA and say, "Well, what's inconsistent about it?" What's inconsistent is that we know, we're not guessing, we're not looking at other data, we know that those untreated children are degenerating. We see it. We see it in time tests, we see it in time to rise, we see it in the 10-meter walk-run, we see it in the 4-stair climb, we see it on the wearable, but you don't see it on NSAA. And that. The reason for that, with the benefit of hindsight, is pretty obvious. It's not that they're... It's not that somehow they're magically not degenerating in one measure versus another. It's that in a 52 week period in this population, NSAA is too coarse and insensitive a tool to detect the decline in the untreated kids that you see everywhere else. And I think when you look at the data, data together, it becomes really clear that that is the case. Not to suggest that NSAA in the long run wouldn't do, wouldn't show it, it just doesn't show it in this population in 52 weeks. And then on the timing of things, the short answer is, they already have the top-line data, and they are committed to moving as fast as possible. We are working on the formal submission part of this. It is my impression that they intend to begin to review the data, even in advance of that submission. So we're very committed to moving as fast as possible, and I believe that our regulators are equally committing to moving as rapidly as possible, and that's extraordinarily important for patients. I would remind you, as Dr. Rodino-Klapac mentioned, when we looked at time to rise, the single most predicted metric for early loss of ambulation is a child going over five seconds on time to rise, and in EMBARK, this therapy reduced the odds of that occurring by over 90%. So it is compelling that we need to move as fast as possible. This therapy was removed, was approved in June. By the end of this year, 200 kids will have lost ambulation that are not treated with ELEVIDYS. So we need to move as fast as possible. I am quite confident that our colleagues at the FDA are equally committed to rapidly reviewing this file, and I'm looking to, if they agree that the data supports it, broadening this label and removing unnecessary restrictions in kids getting it. Thank you. Thank you. One moment for our next question. Our next question comes from Gil Blum with Needham & Company. You may proceed. Hey, good afternoon, and thanks for taking our question. So maybe just on TTR and 10-meter to 10MWR. Was any of this discussed in the earlier filing to the agency? And what gives you confidence that the FDA will maybe reevaluate the tools for assessment here? I mean, NSAA seems pretty established. Thank you. NSAA is an established metric, as is time to rise, as is 10-meter walk-run. Those other secondary endpoints have been used as primary endpoints in other studies. In fact, the literature is quite clear that time to rise, and particularly time to rise over five seconds, is the single most important prognostic tool for determining if a kid will have an early loss of ambulation. And, you know, generally, what gives us confidence that we're confident because of two things. One, we're confident because of the comprehensive evidence in front of us, and two, we have confidence based on the fact that we've had very positive and encouraging interactions so far with FDA leadership. Thank you. One moment for questions. That's my question. If they give me the- Our next question comes from Ritu Baral with TD Cowen. You may proceed. Good afternoon. Thanks for taking the question. Doug, you mentioned something about, something about the nature of the NSAA data in the older patients masking the benefit seen in the time to rise and the 10-meter walk. Looking at the 17 components of the NSAA, I'm sure you and Louise have sort of looked at some of this aspect, like, what in particular about some of these movements may be more difficult for the older boys, independent of, dystrophin and muscle function? You know, I'm gonna let Louise comment on this. I apologize, Louise. I'm gonna comment on it first. You're probably gonna do a better job of it than me. But just so you're very, we're very clear, that the, for instance, rise from floor exists in NSAA. It's just simply, as one can see from the data, that in this 52 week period in the untreated group, the NSAA, while it will work in the long run, in this population in 52 weeks, is too coarse to see, for instance, decline in the untreated group. As an example, look at it, if you look at a subset of kids that are a one on the NSAA, you'll remember there's zero, one, and two. So zero means you can't do it. One. Two means you can do it flawlessly. One means you do it with some modifications, right? If you looked at the kids that are in ones, that started ones and ended in ones, and then you looked at across treated and untreated group, you would see that the, that the untreated group significantly declined versus the treated group, and yet they're both getting ones. Why is that? Is that a failure of NSAA? In a sense, it's not a failure of NSAA, but it is a failure of the tool in 52 weeks in this population. But Louise, you can do a better job than, than I'll do on this topic. You actually took my answer. I think just to make the point that the NSAA, given that it's a zero, one, and two, we just don't have the sensitivity in those time points, like a one that gave, for example, with time to rise from floor, doesn't show you the full breadth of the differences that we're seeing between the treated and placebo. So it really is just this 52 week time point and this measure over that period, which is much more sensitive than the time test. Have you, either in the recent interactions or prior interactions, had specific conversations with FDA on the two-year time point from EMBARK? Say it's something that KOLs have mentioned repeatedly well before the data was read out. To the best of my knowledge, the discussions that we had on these topics occurred after EMBARK. Am I correct on that, Louise? Correct. We did not talk about the two-year time point proactively. Thanks. Thank you. One moment. Oh, and if the question also, someone along the way asked a question about sort of looking at two years. Just so we're very clear, the requirement of a study like EMBARK was that it must be placebo-controlled and blinded. It is nearly impossible, consistent with good biomedical ethics, to run a placebo-controlled trial for two years. We have actually done it in essence, but it is enormously difficult. It is challenged from an ethics perspective, and it wouldn't have been acceptable here. So we're very clear. 52 weeks for a blinded placebo controlled trial is just about as long as one can do and get through IRBs and frankly, satisfy yourself that you're being ethical. Thank you. One moment for questions. Our next question comes from Brian Skorney with Baird. You may proceed. Hey, good afternoon. Thanks for taking the questions. I guess, as you kind of think about moving through the FDA, do you think that they are going to call another ad com to discuss any labeling changes here? And then, on the statement around the secondaries being statistically significant, I thought under the SAP, you would need to hit on the primary endpoint to evaluate secondaries for statistical significance. So is there something about the protocol that allows for a statistical evaluation of the secondaries without hitting on the primary, as opposed to just evaluation for nominal significance? Well, you could, you know, yeah, you can put the word nominal in front of it when there's a hierarchical analysis. The fact is that we did hit P values of 0.002 and 0.004 in both of the pre-specified key secondary functional endpoints. Among all of our endpoints, every single secondary endpoint favored ELEVIDYS, and nearly all of them strongly hit statistical significance. We hit statistical significance at time to rise. We hit statistical significance in 10-meter walk- run. We hit statistical significance on the 4-stair climb. We hit statistical significance on the wearable. If you look at our key pre-specified endpoints, we weren't powered to see stat sig in the subgroups of age, but we did. We saw, I interestingly, stat sig that was almost identical between both of those groups, and strongly so. So we feel very good about the data. On the advisory committee, our perspective right now is there is, there's no need for an advisory committee, and, yeah, certainly in our early conversations, there's been no discussions of that. Thank you. One moment for questions. Our next question comes from Salveen Richter with Goldman Sachs. You may proceed. Thanks for taking my questions. I just wanted to go back to two points that were raised earlier. So with regard to the FDA, and the totality of benefit that they want to see, how, how much was there a discussion around the timed endpoints versus, you know, NSAA variability and the focus on the primary versus the inclusion of these secondaries? Just help us understand how they're going to think about this. And then the second point is, you mentioned the confirmatory data that you just saw for the four to five -year-olds. Is that enough to keep the drug on the market for this age group? I'm just trying to understand the discussion around what needed to be seen for that group. Sure. Let me go to the first one first. So the discussion with the FDA, you know, largely mirrored the discussion that we've had today. So there, of course, was an enormous amount of discussion about the time test, the objective time tests, the statistical significance around them, the clinical meaningfulness of them, and the reason that the NSAA did not show statistical significance, which is related to the fact that the six to seven -year-olds didn't show the decline that they were, in fact, having. So it was all, it was all of those discussions together, and as we said, we had a very positive meeting with them on those topics. And then on. From our perspective, on the level of evidence to justify, you know, confirming for the four to five-year-olds, to answer your question is, is that enough? The answer is yes. Thank you. One moment for questions. Our next question comes from Uy Ear with Mizuho. You may proceed. Hey, guys. Thanks for taking my question. I was wondering, first, just a clarification question. Do you—Doug, did you say that the P value for the secondary endpoints, they're nominal? Is that correct? And secondly, just wondering if, you've, you know, what your thoughts are with respect to, payers. Like, how would they look at this particular set of data, given that it, the primary endpoint did not hit statistical significance? Thanks. Yeah. Yes, thank you for your question. I'll answer the second question, and I'll turn the first question over to Louise. On payers, you know, look, this team has a very good track record of working productively with payers. You know, we have four approved therapies right now, and we've done very well serving the community. So I'm confident generally in our team's ability to work with payers. I'm specifically confident over the strength of the data. You know, the I, I think that this is about as good a data as we've ever, you know, seen in a therapy such as this. And as I've said before, it bears repeating, the literature is quite clear that there are four big prognostic indicators of early loss of ambulation. The most prognostic is time to rise and going over five seconds, and then 10-meter walk- run, and then, the 4-stair climb. The fourth is the six-minute walk test, but the six-minute walk test wasn't performed in this study. As relates to all three of those, we strongly hit statistical significance, creating a very compelling point that this is very clinically meaningful and will change the course of this disease and keep these kids out of a wheelchair. And as we've mentioned before, on time to rise, the most prognostic, of being over five seconds, those kids on ELEVIDYS reduced their odds of an early loss of ambulation by over 90%. So we will have a, I believe, a very good discussion with payers once we've expanded this label. With that, Louise, you can. I'll leave it to you to comment on the P value again. Sure. Yes, technically, when the primary is not met, then the secondaries, I used the word nominal before. That does not negate the data in any way, and that's certainly not something that was brought up in our discussions with the FDA, who are very encouraged by the data, specifically on these objective measures of time tests. It was very encouraging, and they're encouraged by the data. Thank you. Thank you. One moment for questions. Our next question comes from Joseph Schwartz with Leerink Partners. You may proceed. Thanks very much. So I think it was previously communicated that the FDA would entertain a non-age-restricted label if EMBARK, quote, unquote, "meets its objectives." And so I was wondering, first of all, if that was ever tied to a statistical analysis plan, consistent with how you're intending to present these data to the FDA. And then also, the 52 week data are provided here. I'm just wondering if you can comment on whether the NSAA curves are widening or narrowing at this point. Did you measure NSAA at other time points, like 3, 6, 9 months, for example? And do you have any sense as to the shape of the NSAA curve? Thank you. Yeah, I think. Thank you, Joseph, for your questions. The latter question, I think the curves were shown in the slide deck itself, if I'm not mistaken. The short answer is that in all of our conversations, going back, you know, some years, I think it's been understood that evaluating the label is based on the totality of the evidence presented, and that's, I think Dr. Marks has said that publicly many times, so I think this is very consistent with the overall concept. Thank you. One moment for questions. Our next question comes from Anupam Rama with JP Morgan. You may proceed. Hey, guys. Thanks for taking the question. As part of the formal submission, are there any additional key analyses beyond what you've presented today here in the top line, that we should be considering, that you'll be submitting to the FDA? Thanks so much. Louise, I'll turn this to you for that, the answer to that. Yeah. The full data, you know, all of the data will be submitted in the package to the FDA for the supplement. These are the key studies that are identified for the top line, but there's additional data that is part of the full CSR that will be submitted to the agency. Thank you. One moment for questions. Our next question comes from Kristen Kluska with Cantor Fitzgerald. You may proceed. Hi, good afternoon. Heading into the study, you had guided, you know, potentially to see a 1.3-point difference based off a lot of the powering assumptions, what you would need to hit for stat sig. So given that there were a number of trial updates and other factors that you made, can you talk about how each arm essentially performed relative to what your expectations were with these powering assumptions? Sure. Louise, do you want to comment on that? Sure. You're right. So, we presented data that we would need to see a minimum difference based on the assumptions that we had from our previous studies. I think what we saw in this case is the treated arm performing consistently with what we've seen before, and the six to seven -year-olds with placebo arm performed slightly better than what was predicted. But remember, we made the critical decision to include only patients with a time to rise of less than 5 seconds, and so this population is a milder population than previously studied. And so that's, you know, I think everything we're saying here is that the six to seven -year-olds, the NSAA difference just did not pick up what we saw in the obviously declining population that was evident from the time test. It just wasn't sensitive, in this 52 week time point. Thank you. One moment for questions. Our next question comes from Hartaj Singh with Oppenheimer & Company. You may proceed. Great. Thank you. Thanks for the comprehensive presentation. Really appreciate it. Just a question on, you know, the safety slide you had, you presented. Can you just give any more color around it? I know you're probably going to be presenting a lot of this data at future medical conferences. And then I know that age and baseline AAV or stratifications, did you see any differences in any of the AEs or the treatment emergent AEs, you know, using those stratification factors? Thank you. Yeah. Yeah, overall, the data from safety was completely consistent with what we've seen previously. In terms of age, we saw the same nausea and vomiting being the most obvious with some liver enzyme elevations, completely consistent with what we've seen on previous studies. We did not see any age-related adverse events, so it's, you know, very encouraging to see the same, the same profile. And now we have an expanded database of safety to submit to FDA to support our previous approval. Great. Thank you. Thank you for the question. Thank you. Thank you. One moment for questions. Our next question comes from Tim Lugo with William Blair. He may proceed. Thank you for the question. Do you have a sense for how the CK data looks, if it's consistent between the age groups, and do you expect to release maybe CK and expression data prior to the FDA weighing in on the expansion? Yeah, unfortunately, we don't have. I mean, Louise, correct me if I'm incorrect. I don't believe we even have the CK data in-house yet. This is sort of hot-off-the-press data, so we don't have that yet. There is obviously a lot more interesting data in here that we'll get over time, and then we'll be looking to publish it and present it at a future medical meeting. Okay, thank you. Thank you. One moment for questions. Our next question comes from Colin Bristow with UBS, y` ou may proceed. Good afternoon, and thanks for taking the questions. First on time to rise and 10-meter walk, they seem to be trending better in the six to seven -year-olds, which I think is contrary to what we've seen previously and what would be expected. Any comments on this? And then from a regulatory standpoint, I know this has been asked in a couple different ways, but I just wanna press you on this. Like, what is your base case expectation? It sounds like it's full approval in four to five -year-olds, but I just wanted to confirm this. And then from a manufacturing perspective, what will you prepare for in terms of a market size? Will it be this four to five -year-old full approval or removal of an age restriction? Thanks. Yeah, let me touch on this, and then, Louise, tell me if I have missed anything. So first, on the 10-meter walk- run and the time to rise, just so we're clear, from a statistical significance perspective, they are nearly identical, like, surprisingly, overlay one another on statistical significance as it relates to the four to five s and the six to seven s. The fact that it looks like you're seeing an even greater separation appearing in the six to seven s is very likely not because it works better in six to seven s than it works in six to seven s. It's that by the time you get to six and seven, you're now in the normal ferocious decline phase of Duchenne Muscular Dystrophy. And it's at, it's at that point where this disease-modifying therapy that adds the shock absorber, is going to arrest decline while the ferocious decline is occurring in the untreated group. You can see this even on NSAA when you look at the kids in 101. By the time they get out to four years, the difference between them and where they should be, from a degeneration perspective and where they are, is dramatic. So I think it's, it's about that. But what's really encouraging is that from a statistically significant perspective, they are almost exactly with one another. And I think our perspective is that's what you would see across the entire age spectrum, which then gets me to my second answer, which is, you know, our goal is, very straightforward. We don't intend to willingly leave any child or young man behind. This therapy is benefiting these kids. It is changing the course of this ferocious disease, and we think that children and men across the spectrum of Duchenne Muscular Dystrophy deserve this therapy. We're pursuing a label expansion that includes removal of any age restrictions or any restrictions on the basis of ambulation. Finally, let me end to manufacturing, and then Louise will correct me if I've said anything incorrect. On manufacturing, we have been and we continue to plan for the broadest possible label from a manufacturing perspective. Louise? No, nothing to add. Perfect. Thank you. Hey, this is Ian. Maybe just one thing to add around the manufacturing. Obviously, previously, we took a very conservative approach to manufacturing and waited for FDA feedback prior to increasing our capacity and building inventory. As Doug just said, you know, we're taking a very different approach here, and we're gonna be building inventory for the entire population. Thank you. Thank you. One moment for questions. Our next question comes from Michael Ulz with Morgan Stanley. You may proceed. Hey, guys. Thanks for taking the question. Maybe just to follow up on some of the prior questions, regarding the path forward. Just under a scenario where the FDA decides not to grant an expanded label, just curious what your thoughts are there, if you would run another study and maybe use a different primary endpoint, such as the time to rise, for example? Thanks. Well, we're, you know, I think we're hopefully well known by now for being great executors, and certainly as great executors, we think about all scenarios. But the scenario in front of us today, and the one we are focused on with all of our energy, is to move as rapidly as possible to finish the submission, engage with the division and the FDA, and expand this label by removing age limitations or artificial ambulation restrictions so that this therapy can be beneficial to children across the spectrum, from young to non-ambulatory. And that is what we are single-mindedly focused on as an organization right now. Got it. Thank you. Thank you. Thank you. As a reminder, to ask a question, please press star one one on your telephone. One moment for questions. Our next question comes from Gavin Clark-Gartner with Evercore ISI. You may proceed. Hey, thanks for fitting me in. So on your FDA discussions to date, were there any different conversations on expanding the label to all ages versus expanding it to all ambulation statuses? I'm just trying to get a sense if the FDA views both of these label expansion aspects together or if they may be separate considerations. Thanks. Well, I think that they are. In one sense, they ought to be interrelated, but in the current label, there is a restriction for ambulation and a restriction for age as well. It is our perspective, and, you know, certainly FDA leadership is well aware of our perspective. We were not timid in discussing it, that EMBARK has confirmed the mechanism of action of ELEVIDYS. It has shown that ELEVIDYS is effective in altering the course of this disease across the ages study, and its mechanism of action would certainly support the conclusion that it's going to continue to benefit kids across the entire journey of Duchenne. And that's on the age side, but on the ambulation side, it is no different. You know, to be snarky, this, ELEVIDYS doesn't know that you're in a wheelchair versus you're out of a wheelchair. It is a shock absorber that protects your muscles when you move. The point of EMBARK was to prove that this mechanism of action works, and there's nothing unusual about it that would make it work better in four to five s than it would in six to seven s or eights to nine s or 10s to 11s or non-ambulatory. And so long as a person has muscle that can be protected, they can benefit from ELEVIDYS. And on that basis, we've. The conversations we've had for them, with them, is that we believe that the ambulation restrictions and the age restrictions should be removed, as they do not exist in other Duchenne-related therapies that have been approved. And that's been the basis of our discussions. Thank you. One moment for questions. Our next question comes from Gena Wang with Barclays. You may proceed. Thank you for taking my follow-up questions. I have two questions. The first one, I wanted to go back to the two-year assessment. Doug, you said, you know, I totally understand it's very difficult to do the two-year assessment, given patient will cross over at one year. Is there any possibility or any way to assess, say, you know, with mixed patient population, and then you look at a one-year patient on treatment versus two-year patient on treatment and see the separation? You know, it's, because the core thesis here is that, you know, all the other measurements, there is an earlier effect or more sensitive, and we should see a North Star at a delayed fashion, that we should be able t o see the separation of a clinical benefit. So that's the first question. Second question, actually very important. For the rest of the world or the EU, have you discussed with Roche, and what will be the feedback there regarding the regulatory path? Yeah, so on the first one, look, there, you know, just so we're clear, we're going to be tracking the children in this study for years to come. And there are lots of different kinds of assessments one can do over time. But so we're very clear, as we stand here today, our goal is to seek a broad label without restriction to age and ambulation on the basis of the evidence in front of us today, because we believe the evidence in front of us today is compelling and justifies that, and that's what we're going to do. And then, as relates to rest of world and Roche, I think Roche has issued their press release today. You can see that they are encouraged by these results, and they intend to talk to their regulators about their path forward. So, they're proceeding as well. Thank you. Thank you. Thank you. I'd now like to turn the call back over to Doug Ingram for any closing remarks. Thank you very much. Thanks, everyone, for joining us this evening. Thank you, Dr. Regina Klebeck, for sharing the results with us as well. And by the way, thanks to all of the families and clinical investigators who have participated in our many studies, including EMBARK. You really are pioneers for the rest of the community. So I'm gonna give you our perspective, and we've said it a number of times, but I do think, at the risk of being repetitive, it bears repeating. Our perspective on EMBARK and next steps are quite clear. First of all, every EMBARK measure favors this therapy, ELEVIDYS. Every key secondary endpoint is strongly statistically significant, as are all of the age subgroup analysis in the key secondary endpoints, even though they were not, in fact, powered to be statistically significant. Across all of the endpoints that most powerfully predict loss of ambulation, to remind us, that's time to rise, 10-meter walk- run, 4-stair climb, ELEVIDYS is powerfully statistically significant. As the literature notes, a rise time that slows beyond five seconds is the single most predictive metric for early loss of ambulation, and ELEVIDYS reduces those odds by literally over 90%. While we did not hit statistical significance on NSAA, it is clear, I mean, you can look at the curves and see it, that this is because NSAA was simply not as sensitive as the various time tests, and indeed, too insensitive to pick up the decline in the six to seven -year-old age group in 52 weeks that every other timed metric detected in these degenerating boys. Fortunately, we have, as you know, a wealth of more sensitive tests that showed the benefits of ELEVIDYS in 52 weeks and across all of the age groups. This is indeed a scientific inquiry, and the evidence, in our perspective, is simply overwhelming, subject to that scientific inquiry. And so we intend to move quickly, and we are confident that our regulators will match us in the rapidity of review and objectively review this application with an eye to expanding this label. With that, I would like to thank everyone, and ask you to have a good evening, and I look forward to speaking to all of you again in a mere 48 hours on our quarterly, earnings conference call. Thank you. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.