Good afternoon, ladies and gentlemen, and welcome to Sarepta Therapeutics SRP-9001 New Clinical Data and Integrated Analysis conference call. After the speaker's presentation, there'll be a question and answer session. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Doug Ingram, President and Chief Executive Officer. Please go ahead. Thank you, Michelle, and thank you all for joining us today for a review of our most recent results regarding the functional benefits and safety of SRP-9001, our gene therapy. After literally a decade and a half of rational design, testing, optimization, brilliant preclinical evidence, and then repeatedly confirming across multiple studies SRP-9001 safety and efficacy profile, we at Sarepta have developed, as you can imagine, a significant conviction in the potential of SRP-9001 to change the trajectory of this disease, Duchenne. You can also imagine how difficult it would be to exceed our expectations in the transformative potential of this therapy. Yet the results that we will be discussing today have done just that. They have met or exceeded our expectations on every vector considered. We see impressive, statistically significant and clinically meaningful results. We see results using our commercially representative material at target dose that meet or even exceed our prior clinical material experience. We see results that bolster even further the powering of our ongoing placebo-controlled trial, EMBARK, a trial that was already robustly powered. We see results that diverge from natural course of disease so that the impressive results we see at one year grow greater as the trajectory of the treated children diverge from the natural course of this ferociously degenerative disease. We see a stable and differentiated safety profile. The potential meaning of these results to the lives of Duchenne patients should be patent to all of us. With that, let me turn the call over to our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac, who will walk us through the results. Dr. Rodino-Klapac. Thank you, Doug. Good morning, and thank you for joining us today. It's with great pleasure that we share with you new clinical data for SRP-9001, our gene therapy in development to treat individuals with Duchenne muscular dystrophy or Duchenne. The data from our 103 study is particularly important because it's from our commercially representative material. It can be extremely challenging to achieve the same level of safety and efficacy when scaling up from small scale to commercial scale. We are thrilled to see that these results are not only consistent, but may be improved over previously reported results. This is a shining moment for the program, so I wanna thank all of our CMC colleagues for all of their contributions. Here are forward-looking statements. I or one of my colleagues may make statements or predictions about future events today. Please review our public filings for the risks that may come with these sorts of forward-looking statements. Now, in terms of the agenda, today's presentation includes the following new clinical results. For SRP-9001-103, our ENDEAVOR study, we'll be sharing results from cohort one's 20 patients one year functional data from baseline and compare it to external control. For SRP-9001-101, it's four year follow-up data from our first four patients, which includes NSAA and timed function test. From study SRP-9001-102, part one, 20 patients, two year functional data. Finally, our integrated efficacy analysis, which includes Study 101, 102, and 103 at target dose in 52 patients, and this includes one year functional data compared to propensity-weighted control. We will also touch upon the expression results from all of these studies and review our safety data, which continues to be a key differentiator for our program. Duchenne muscular dystrophy is a devastating disease. SRP-9001 is intended to not merely treat, but to change the course of this progressively degenerative disease. Duchenne results from a mutation in the gene that codes for a protein called dystrophin. Dystrophin is a sort of shock absorber in our muscles. It attaches to the sarcolemma or muscle membrane and distributes force as we move, protecting our muscles from damage. Boys with Duchenne lack this dystrophin shock absorber to protect their muscles, and the consequences are as certain as they are brutal. The course of the disease is predictable. At a young age, a Duchenne boy will begin to struggle. Sometimes typically between 10 years of age and very early teens, he will become wheelchair dependent, followed by respiratory and cardiac complications, and ultimately death will follow, typically in the third decade of life. Our goal is to change all aspects of this cruel disease with SRP-9001. We believe today's clinical results advance us one step closer to changing the course of this disease. SRP-9001 is a full body or systemic infusion of gene therapy. It uses a specific gene construct, which is designed, empirically tested, and optimized after decades of research. It delivers a gene cassette that codes for a truncated but functional form of dystrophin to skeletal, diaphragm, and cardiac muscle. It's the only therapy in development that uses RH74 as its delivery vector and an MHCK7 promoter to drive expression. It is these unique and rationally designed elements of SRP-9001 that explain why this therapy results in properly localized expression of the dystrophin protein across muscle, why it has a differentiated and unique safety profile, and why it results in the functional improvements that we have seen in multiple studies to date. Sarepta has dosed more individuals with Duchenne than any other gene therapy currently in development. Today, we will discuss new clinical results from Studies 101, 102, and 103, as well as an integrated analysis of all of these studies. As a reminder, Studies 101 and 102 use clinical material, as shown in the blue circles, and Study 103, commercially representative material, as shown in the purple circles. Our EMBARK study, or study 301, as seen in the last column on the right, is advancing well and on pace. For these analysis, we'll be using pre-specified external control analyses. Due to the lack of a placebo arm in Studies 101 and 103, we used a rigorous propensity-score matching analysis to compare the treatment effect of SRP-9001 against an external control for Studies 101, 102, and 103. The propensity score method is a validated and commonly employed method to reduce bias and precisely predict treatment effect. Propensity weighting has served as the basis for approval of two drugs, Defibrotide for veno-occlusive disease or VOD, and Burosumab for the treatment of X-linked hypophosphatemia or XLH. The external control group includes data from the CINRG Duchenne Natural History Study, the FOR-DMD study, and the placebo arm of an Eli Lilly study evaluating a treatment for Duchenne. All patients in the external control group received steroids. The inclusion and exclusion criteria rigorously match baseline characteristics. The propensity score weightings included age, NSAA, rise from floor, and 10-meter walk run, which are all prognostic factors in Duchenne that are known to impact the progression of the disease. As a second step, a linear regression model is used to correct for any remaining imbalances in baseline covariates. Now turning to Study 103, also called ENDEAVOR. Study 103 is an open-label clinical trial of SRP-9001. The study has enrolled 40 participants with Duchenne, including 20 ages four to seven, an expanded cohort of older ambulant and non-ambulant individuals, as well as a younger cohort. Today, we'll be showing functional data results from the 20 patients in cohort one between ages four to seven who are ambulatory. As a reminder, we presented the first functional results from Study 103 in the first 11 participants in cohort one, ages four to seven. We demonstrated a three point improvement from baseline on NSAA just six months after treatment. In terms of our baseline covariates, as you can see, the propensity score weighted balanced the baseline variables well for the SRP-9001 arm and the external control arm. The baseline functional characteristics for both arms are nearly identical for all measures. Now for the data. We are thrilled to report that patients in cohort 1 of the ENDEAVOR study improved four points from baseline on NSAA. Pre-treatment, they had a mean baseline NSAA of 22 at week 52, improved to a mean of 26, which is approaching the top end of the NSAA scale. To put these data in context, for example, these patients can now perform two activities unassisted that they were not able to perform prior to therapy, or four activities that they needed assistance with that they can now do on their own. Equally impressive, SRP-9001 treated patients improved 3.8 points using unadjusted means and 3.2 points using least squared means at 52 weeks on NSAA compared to the propensity-matched external control, which is highly significant with a p- value of 0.0001. Simply put, the unadjusted mean difference is the mean change from baseline of the SRP-9001 treated group, minus the mean change from baseline in the external control group. The least squares mean difference is commonly used for multivariate analyses to account for any imbalance. These results demonstrate that commercially representative SRP-9001 improves motor function and further confirms our confidence in the treatment effect of our therapy, increasing the probability of success for EMBARK. We've also seen mean improvements across key secondary functional endpoints, including Timed Test. Shown here, Study 103 demonstrated mean improvements across these endpoints, which include Time to Rise, 10-meter walk/run, Time to Ascend 4 Stairs, and 100-meter walk/run. In summary, patients receiving SRP-9001 improved significantly on every functional measure. The external control sets only collected Time to Rise and 10-meter walk/run data, so these are the only two analyses available using external control. For Time to Rise, we observed that SRP-9001 treated participants improved 0.9 seconds on unadjusted means and 1.2 seconds on least square means at 52 weeks compared to the propensity-matched external control group with a p- value of 0.0001, which is highly significant. Now for the 10-meter walk/run, we observed that SRP-9001 treated participants improved one second using unadjusted means and also one second using least square means at 52 weeks compared to the propensity-matched external control group with a p- value of 0.0018, which is also significant. In summary, the results of Study 103 are truly remarkable, and our conviction is further strengthened by the consistency across all measures. Now I'll turn to our long-term data results. These data are particularly important because they answer two of our most common questions. Question number one, are the data clinically meaningful? The second question, is the effect durable? First, we will look at our original four patients after four years of treatment on SRP-9001 from Study 101. To remind you, SRP-9001-101 is a single-center open-label clinical trial to evaluate the safety, tolerability, and proof-of-concept of a single dose of clinical process material. The trial enrolled four ambulatory participants between the ages of four to seven. Participants are being followed for five years after treatment, while safety and efficacy continue to be evaluated. I will be showing you two analyses for Study 101, NSAA change from baseline over four years in the four treated boys, and then in comparison to external control group using propensity-score weighting. First, once again, you can see that the propensity-score weighting has balanced the baseline functional characteristics well for both groups. Now turning to the data. As noted on this slide, the data show that patients in SRP-9001-101 demonstrated a mean increase of seven points in total NSAA from baseline to year four. I'd like to pause here because these data are particularly important. As these are older patients, around nine years of age at year four, and because Duchenne is a disease that gets progressively worse, these patients would now be in the steep decline phase of their disease. However, instead of declining, they have increased their function and importantly maintained that increase, thereby demonstrating a distinct treatment effect that increases over time, supporting the durability of SRP-9001. We are showing individual patient-level data here, so it's clear that all patients have remained stable and well above their baseline for this time period. No single patient is driving the mean of the group. We are pleased that all participants are continuing to benefit four years later. Now, when we compare the treated patients to the propensity-matched external control, we observe a nearly 10-point difference using unadjusted means and a 9.4-point least square means difference with a p- value of 0.01 at four years. As an example, SRP-9001-treated patients can now do five activities that those in the external control group are not able to accomplish. The durability question needs no further explanation. I will spend the bulk of the time on the clinically meaningful question. We are pleased to see that the treatment effect has continued to increase over time. We feel confident that we can detect a statistically significant difference at one year. However, this time period does not define the total clinical effect of SRP-9001. As expected, and as shown on the graph on the left, the treatment effect increases over time. Importantly, please note the precipitous decline in year three and four of the external control group as these boys are now in the steep part of the decline phase of their disease, while the treated patients remain stable. This graph represents the treatment effect of a disease-modifying agent. To further support this point, next, we'll share the functional results from 20 patients who have received SRP-9001 in part one of Study 102 and now followed for two years. As a reminder, Study 102 is a double-blind, 1:1 randomized, placebo-controlled clinical trial of SRP-9001 in 41 participants with Duchenne between the ages of four to seven. We again analyzed the propensity score weighting method to compare NSAA data for Study 102, part one participants to an external control group. Once again, the groups are very well-matched. At one year, as noted on this graph, in Study 102, part one, there's a three point median difference between the SRP-9001 group and the external control group. At week 96, this grew to a five point median NSAA difference with a p- value of 0.0001. It's also important to note that an influential outlier with a 17-point NSAA decrease was observed in these data, which skewed the mean estimate, and therefore, the comparison of the medians are more appropriate when quantile regression was applied using the same propensity score weight to test the equality of a mean. It's important to note this patient would have been excluded by 301 inclusion/exclusion criteria. The fact that only approximately half of the patients in the treated group received the target dose make these results even more impressive. Now, speaking of target dose, we will now move to the integrated efficacy analysis for all patients in Studies 101, 102, and 103, who received a target dose of 1.33 × 10^14 vector genomes per kilogram compared to an external control. When you pool all of the patients who received a target dose from these studies, from 101, 102, and 103, we have a robust pool of 52 patients in the corresponding analysis. In terms of the baseline covariance, unsurprisingly, once again, the groups are very well-matched at baseline. The integrated analysis of one-year functional data from patients who received the target dose of SRP-9001 in Studies 101, 102, and 103, the treated patients improved 2.4 points in NSAA total scores from baseline. When compared to the propensity weighted external control group, NSAA changed from baseline one year after treatment for the treated patients was 3.1 points higher on unadjusted means. Two point four points higher using least square means with a highly significant p-value of 0.0001. These data firmly reinforce the consistency of NSAA improvement now across three independent trials. Again, we also looked at key secondary functional endpoints for the time function test. Importantly, these data show mean improvements such as time to rise and 10-meter walk run. Now, to conclude this section, we're showing expression data across all of our studies. We are very pleased with the consistency of the results generated from both our clinical and commercial manufacturing process with study one of three. Finally, I will now share an update on safety. Our collective safety data shown here has been generated from all patients in SRP-9001-101, SRP-9001-102, and SRP-9001-103 for a total of 84 patients. The most common treatment emergent adverse event was vomiting. We had one new treatment-related SAE myocarditis in an 11-year-old boy admitted to treat his nausea and vomiting. While the patient had no symptoms or signs of systolic dysfunction, raised troponin was noted incidentally during his hospitalization. Function was preserved on echo and cardiac MRI, but MRI findings were consistent with myocarditis superimposed on Duchenne cardiomyopathy. The patient received 3 days of IV methylprednisolone. Post-event, he had additional chronic cardiac medications added, and cardiac MRI at 1 month showed normal function with partial resolution of myocarditis changes. An echo at four months showed normal systolic function. We have now dosed the largest number of Duchenne patients and have dosed patients over 80 kilograms. We continue to see no clinically relevant complement activation, and we remain pleased with the strength and consistency of SRP-9001 safety profile. We will end with a summary of today's data and next steps. These new data and our integrated efficacy analysis have demonstrated that SRP-9001 performs well above what natural history would predict, giving us increased confidence in the probability of success for EMBARK, our global phase III pivotal trial. We remain on track to complete enrollment in the EMBARK study in the middle of this year. Finally, we remain in discussions with FDA regarding a potential accelerated approval submission. We will provide an update when the discussions conclude. Thank you very much for your attention today. I will now ask the operator to open the call for Q&A. If you would like to ask a question, please press star then one. We ask that you please limit yourself to one question. Our first question comes from Anupam Rama with JPMorgan. Your line is open. Hey, guys. Thanks so much for taking the question. Across the totality of the data across the various studies on NSAA, I know you put the benefits into context. Are there any trends on which domains are improving within the endpoints and any differences there age-wise or otherwise? Louise? Thank you for that question. We certainly look across the domains. As you'll note, given the totality of this evidence and 5-point changes, you're seeing a positive effect on multiple domains within the analysis. As we mentioned, you're showing improvements in multiple and then also gaining these effects. There's no particular domains that we see improvement in that we don't see in others. Across the board, we're seeing improvement. Thanks so much for taking our question. Our next question comes from Ritu Baral with TD Cowen. Your line is open. Good morning, guys. Thanks for taking the question. I wanted to just ask about controlling for steroid use in the propensity match controls versus the dosing that's used around SRP-9001 treatment. Did you look at what steroid dose the propensity matched controls were using and if the difference might impact the delta on NSAA? Just a very quick follow-up question from a client. The timing of the FDA discussions that you've had so far about when were they? Were they very recent, or were they earlier this year? Thanks. Yeah. I'll answer the last question, then I'll turn the steroid related question over to Louise Rodino-Klapac. I'm gonna give you an exact timing, but we've had some productive discussions with the FDA. We've had an opportunity to share with the FDA all of the information that you have seen today. We wanted to make sure that the FDA had an opportunity to review that and digest it before we publicly disclosed it, and that's why we chose this meeting to do that. As I've said before, I will say it here. We've had some productive discussions with the FDA. We're continuing to be in dialogue with the FDA, can make no prediction on the outcome of that, but I am confident that we'll get to a conclusion in a relatively, you know, not too distant future. Of course, we'll provide an update once we do. The exciting thing about this data. Frankly is across all of the various studies and then looking at the prior data that we've disclosed as well. But really focusing on this data here is that it certainly is helpful in discussions with the FDA regarding the potential for filing whether for accelerated approval, but also beyond that issue, just with respect to EMBARK. EMBARK was a very well powered study. These results only increase our conviction and frankly increase the powering of that study. We're very excited about what we're seeing here, and we'll provide an update on those discussions with the FDA once we have a conclusion on them. With that, Louise, perhaps you can touch on the steroid-related issue. Sure. Regarding the steroid uses in those external controls, they were using standard of care dosing, which is consistent with what our patients are on. Now, our patients in the first 60 days do get increased steroids, but at the time point we're looking at one year, they're all on standard of care and well past that period of using those increased steroids so that it wouldn't confound the treatment effect. Awesome. Thanks. Mm-hmm. Our next question comes from Colin Bristow with UBS. Your line is open. Hey, good morning, and congrats on the data. First, somewhat of a housekeeping question on patient numbers. I think there's 65 patients across cohort one for 103 and then Studies 102 and 101. In the pooled analysis there were 52. I didn't quite see the footnotes on the slide. Could you just help me with that delta? And then just a quick one on the functional data for 103. Can you talk about any differences or any meaningful differences in ages and baseline characteristics for the additional 9 patients we got today versus the original 11 that comprised the 24-week data we saw at the micro-dystrophin day? Thanks a lot. Yeah. Louise, do you wanna take both of those? Yeah. The first question around the numbers of patients. In the integrated analysis, we included all patients that were on target dose, and that's how we arrived at the 52 patients for the integrated analysis. The baseline characteristics for the 11 versus the 20 are similar. As you know, we had added more four to five-year-olds when we went to 20 patients, and so the mean age is slightly lower than the first 11, but relatively consistent with the first 11. Sorry, just on the target dose issue, what was the primary reason for patients not receiving the target dose? Thanks. Yeah. In Study 102, if you'll recall, when we retrospectively titrate those patients using our now validated methods, it was noted that there was some variability in the lot using the clinical material in part one of that study, and that's why there was some patients that received less than the target dose. Okay. That's it. That's great. Thank you very much. Just so I'm sure everyone knows this, but please suspend the doubt. We started Study 102, part one using clinical supplies from Nationwide Children's Hospital, and we used the titer method that they had, which at the time was a supercoiled PCR method. Between part one and part two, we were able to develop a much more precise titer method. All of the kids at crossover received the linear titer method that we developed, and they all had target dose. The kids in part one, as Louise mentioned, 60% of those kids had less than a target dose. All of the kids in 103, of course, are not only at the target dose, but that's our commercial process material. That is the process we'll be using to launch this therapy, and that is the dose we would intend to launch this therapy at. It's very telling that we're getting these results in that cohort of patients and of course a very robust cohort as there are 20 patients in cohort 1 of 103. Our next question comes from Kristen Kluska with Cantor. Your line is open. Hi. Good morning, everybody. Congrats on these data that you presented. Could you talk more about the importance of the earlier intervention here, especially that you have follow-up with patients for over four years, and you've also looked at different patients across different age groups? I understand that PPMD very recently submitted a nomination package to add DMD to the newborn screening panel. Let me comment very briefly on it, and then Louise can talk a little bit more about the, you know, age-related issues and the like. First, know this, you know, we are working with our with PPMD and others to try to get newborn screening in place, and there's an enormous amount of value in newborn screening for Duchenne. As it relates to this particular data, the real point of this data, when you look at one year versus two year versus three years now versus four years, it's not. There's a separate issue from when you intervene. The real issue is that we are seeing a strong benefit at only 48 weeks. What that miss is that that benefit is going to compound as kids have been on the therapy for a longer period of time because against natural history, they're gonna start diverging considerably. That was one of the things we had previously been saying that, you know, you deduce a treatment effect, you see a three-point delta in NSA, which is brilliant at one year. It would be brilliant. That doesn't describe the benefit because, of course these kids now, if they're on a disease modifying therapy, and if SRP-9001 is anything and is effective, it's disease modifying. These kids are now diverging from natural history over time, and that's exactly what we see. You see on median at two years, you see a five-point delta versus a propensity matched natural history cohort. When you look at these 101 kids, you're out here at four years, and it's really as much about the time on therapy than the age they were dosed. These kids are four years. They're now over nine years old on average. Anybody who knows Duchenne knows what that means for kids that have Duchenne muscular dystrophy. They are in that steep decline phase of Duchenne, and yet these kids are not right now. These kids have been rock solid stable for the last couple of years. They're seven points above their baseline from four years ago, and they're almost 10 points above natural history using a very conservative propensity match approach. The biggest point is that the benefits that we are seeing here confirm at least our hypothesis that the benefits are gonna continue to compound as these kids diverge from the natural course of this disease over the long history of Duchenne. Louise, maybe you have some comments on sort of intervention times? Yeah. I think you touched a lot. I'll just add that, regardless of what age patients have been treated with 9001, we've seen a similar treatment effect in comparison to well-matched natural history control. The age of treatment is not indicative or not mandatory in terms of seeing that benefit. As newborn screening comes on board in the future, I think the opportunity to treat patients earlier is certainly something that we're supportive of and would recommend, and it's great for patients to have that opportunity to be treated earlier as the future comes on board. Thanks. To get the full experience, we, you know, to really fully understand the experience of both expression and safety, and ultimately function across age groups, you know, people should know that we have dosed much older children and young men. We've dosed young men that are nearly 20 years old. We've dosed very heavy individuals over 80 kilograms, and we've also dosed very young. We've actually dosed down now to three years already. We're really building out a very comprehensive set of experience on both expression and safety and ultimately on function with 9001. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open. Hi. Good morning. Thanks for taking my questions. Just to follow up on your comment about not clinically relevant incidents of complement activation, can you just give us a little bit more color on what the threshold is for you to determine what's clinically relevant? Can you just give us some color on the new incidence of myocarditis that was observed in the study? Thanks. Sure, Louise. Yeah. In terms we haven't seen complement activation, so we haven't seen any clinical signs of activation like things like TMA that have been seen in other studies. We just haven't seen any clinical signs of complement activation. In terms of the patient with myocarditis, this was an 11-year-old boy who was treated in the second cohort of 103. This is the older ambulant cohort. He was in the first week, which is common, had nausea and vomiting and was admitted for IV. During that stay in the hospital, he was noted that he had an elevated troponin, but he had no symptoms or signs, and his cardiac function was normal. Out of caution, he received 3 days of methylprednisolone, and now at four months has returned or has normal function. Continues to have normal function on echo. To this point, it was observed incidentally, but clearly something that we do already monitor for troponin and will continue to monitor for in the future. Just one thing to add, this being the way that we're describing clinical complement activation is the exact same way that we've done previous disclosures. There's absolutely no change to how we're describing it now. Yeah. Just for the avoidance of any doubt, we've seen no clinical complement activation. We've never had that. That is not an issue thus far with our therapy, even though we've dosed now, you know, well over 100 patients. We've dosed the largest patients, I think, in Duchenne. We've dosed the youngest patients in Duchenne. We've dosed the oldest patients and the lightest patients. We just have not seen in Duchenne clinical complement activation or TMA or any of the kidney issues that others have observed with other vectors. Our next question comes from Brian Abrahams with RBC. Your line is open. Hey, guys. Congrats on the updated data, and thanks for taking my question. Maybe just to follow up on the patient who experienced myocarditis. I'm curious, what do we know about their mutation? Is this one of the zero dystrophin mutations that had been associated with myocarditis from other programs? If not immune related, any mechanistic explanation there? Also wondering the degree of FDA and EMA awareness of that case and whether or not any additional monitoring, be it more troponin draws or imaging, might need to be implemented for the ongoing phase III. Thanks. Louise? Yeah. Troponin elevations can commonly be seen in Duchenne. We have seen them at predosing in some patients. This patient does not have a mutation that would be subject to immune-mediated myositis, and so that's not something we have a concern about in this case. We already monitor troponin very frequently, and so that's something that we'll continue to do. And certainly this information on these cases have been shared with regulatory agencies. Our next question comes from Gena Wang with Barclays. Your line is open. Thank you for taking my questions. Also, congrats on the data. One is clarification question. For Study 102, you have 28-patient analysis with the correct dose. The placebo arm is 21-patient crossover. Does that mean seven patients from active drug arm actually received the correct dose? My second question is regarding the North Star of the control arm, external control arm. Wanted to understand when you have a multiple year follow-up, do you match with the beginning patient baseline as a control and follow with this external control for full year data, or do you match at when, you know, say one year follow-up, when you have a two-year follow-up, you match with the two-year age to the external natural history as your control? Yeah. Do you have those, Louise? For the second question, we match from baseline, so the propensity-matched controls. They're not rebaselined year-over-year. It occurs as a true baseline. The question on Study 102, part one, as we said, 60% did not receive the target dose in part one. For part two, all patients received the target dose. Our next question comes from Tim Lugo with William Blair. Your line is open. Oh, thanks for taking the question. Good morning and congratulations on the data which continues to improve. I guess the question on the nausea and vomiting patients, it looks to be about 40%-60% of these patients could experience some of this. Can you give us some color on how many of those patients eventually require IV fluids and hospitalization? For the myocarditis patient, would that patient have been picked up if it wasn't for the hospitalization? Yeah. The nausea and vomiting is common. We have not seen this. This was the only SAE in this case that has required hospitalization for the nausea and vomiting, so it's not a common occurrence. Usually it can be controlled with the antibiotics and patients do fine with that. This case, troponin is measured. This was an off-cycle time point, but it would've been potentially caught by the next time point in terms of the troponin elevation with the current existing monitoring within the protocol. It's sort of identified during this time, but would potentially be caught by the next time point. Again, the patient, this was incidental and, you know, he did not have any related function increase. Our next question comes from Yanan Zhu with BTIG. Your line is open. Hi. Good morning. Thank you very much for taking the question. I think on your discussion with the FDA on the accelerated approval pathway, outside the functional data that you presented this morning, do you think you would need, or do you plan to submit anything specifically to support a correlation between micro-dystrophin expression? I assume that that will be the surrogate endpoint and clinical benefit. And also on using the external control, there was a previous question on the steroid use, but I wonder, can you remind us when the external control data were collected and anything that can potentially may have improved over the years in terms of standard of care outside steroid use might affect the validity of the comparison, please? Thank you. I'm gonna touch briefly on the second part, but then I'll let Louise really dig into it. Just so we're clear, those are the kinds of things that one has to be careful about and make sure we're balancing for. You know, there is a cutoff date on the types of information we can use so that we're not going back so far in time that literally standards of care could have changed in some way that confounds the data. I'll let Louise touch on that in more depth than that. On the first part of the question about discussions, the short answer is we've had very robust discussions with the agency, and we've had a significant amount of analytics on the data that we have, expression, safety, associations between various measures and functions. We're in active dialogue with the agency, and once we have an answer one way or the other on the filing of a BLA short of EMBARK, then we will certainly discuss that, and we'll let everyone know. Until such time as that could occur, we should all remind ourselves that our current pathway to approval would be EMBARK. You know, we're very excited about EMBARK. We're obviously dosing EMBARK even as we speak. We'll have a readout in the middle of next year on EMBARK and of course, while we were very confident in the powering of EMBARK before this data, you can only imagine how confident we are today on EMBARK. We're excited about the you know any of the pathways, but obviously the pathway that could bring this therapy to patients the quickest is our ultimate goal. With that said, Louise, perhaps you wanna touch a bit on the external control issue that was asked. Sure. I don't have much to add other than the fact that when we derived the external control data sets, obviously we looked for rigorously controlled trials that used standard of care dosing. We certainly wouldn't review something that wasn't an old method or inconsistent with what's done now. Obviously, we will, you know, evaluate that moving forward. As I mentioned, the early steroid use in the trial does not affect the time point at one year when we're looking at these functional changes. We don't have any concern about that confounding the data in any respect. The other thing we should say about the use of external controls and the way we're doing it is this is a very rigorous but also very conservative approach. You know, the alternative to this approach would've been essentially a post hoc analysis where you grab an external control and you try to match them on one or two covariates. We've gone much more sophisticated than that as number one, it was all pre-specified, so this was all pre-specified analytics. It wasn't post hoc. Number two, on the way we're doing this, that we use a regression analysis with it, which in some regards, you know, arguably dampens the overt effect, but also has the benefit of being very rigorous. In fact, at least two therapies in the not too distant past have been approved on the basis of this pre-specified propensity matched analysis and regression analysis that we're using here. I think we feel very, very good about the approach that we've taken and we think that it has an enormous amount of rigor with it. As a reminder, to ask a question, please press star then one. Our next question comes from Judah Frommer with Credit Suisse. Your line is open. Hi. Thanks for taking the question, guys. I was hoping you could just circle back and maybe provide a little more context on the two drugs you mentioned that were approved on propensity-matched controls. Anything you'd call out in terms of differences or similarities, maybe in, you know, level of unmet need, patient population, anything that you could use as kind of a guidepost for a potential accelerated approval here. I'll let Louise touch on it specifically since she knows the names better than I do of those two drugs. I will say on the concept of unmet need, it's very difficult to get a greater unmet need than in Duchenne muscular dystrophy, a ferociously degenerative disease which is inevitable in its the fatality. With that said, Louise, is there anything else you wanna say about the particular therapies? Yeah. Just in both of these are for rare diseases in patients in pediatric and adult populations, in terms of the rarity, not more rare than Duchenne and no more unmet need than ours. These are both reviewed and those approaches were accepted by EMA and FDA. It's certainly a guidepost. There are some differences, but in terms of the unmet need, they don't surpass that of Duchenne certainly. Probably more than anything else, the point of mentioning the other therapies that have been approved versus this propensity matched approach, it isn't that our therapies are exactly the same or our populations are identical. It's to say that this is a very rigorous and sophisticated approach that creates, in essence, essentially a synthetic placebo and provides a lot more rigor than one might use, for instance, with a simple post hoc analysis where you grab some, you know, patients and have a natural history cohort. You know, I think the point here is that the FDA and I think EMA as well has embraced the concept of a propensity matched external control at times. Our next question comes from Joseph Schwartz with SVB Securities. Your line is open. Hi, this is Beth on for Joe. Thank you for taking our question. I was just wondering if you've been able to glean any insights on how micro-dystrophin expression may correlate to NSAA benefit based on the 12-week biopsy samples you've taken. Also wondering if you've taken any longer term biopsy samples to understand how the micro-dystrophin expression may play out at longer time points. Louise? Yeah. Great question. Certainly, we look at a population level at micro-dystrophin expression, SRP-9001 dystrophin expression versus NSAA, and it's clear from the data today that the expression is driving those functional results. We will be, we've looked at longer time points in the study, in other studies, and then that will be, you know, shared in the future as we publish data sets moving forward, specifically on the 102 data. What we know about durability from those preclinical studies and clinical studies is that AAV in particular is very durable and the results we've seen so far are very consistent with those results, so we're happy with that. I would now like to turn it to Ian for an email question. Sure. Unfortunately, Gavin from ISI couldn't log on to the call, so I'm just gonna ask his question that he asked Louise. He asked in Study 103, do we see a difference in MFA improvement from baseline in the four to five year-old group versus the six to seven year-old subset? Yeah, thanks for the question. We actually didn't do that analysis, as we've seen or see an effect regardless of age in 103. We're seeing an effect size in comparison to the external control that's robust regardless of the age. We did that with some previous analyses in 102. That was confounded by some baseline imbalances. As you can see from this data, we're seeing robust results regardless of the baseline age in this group. Our next question comes from Ritu Baral with TD Cowen. Your line is open. Hey, guys. Thanks for taking the follow-up. Louise Rodino-Klapac, I wanted to just round back to the myocarditis patient. Can you tell us how long it took for that patient to biochemically resolve, and for troponins to come back to, I guess, normal levels? On follow-up, did function return to baseline levels in this patient? Thanks. Yeah. Yep. Thanks for the question. The troponin elevation resolved quickly, and the function remained normal. As mentioned, at one month and one year there was normal systolic function. The function actually never was adverse in terms of this case. There was some myocarditis changes on MRI, but the function had already remained normal throughout the event. Our next question comes from Danielle Brill with Raymond James. Your line is open. Hi, guys. Good morning. Thanks for the question. I just have a follow-up as well on the myocarditis patient. Sorry if I missed this before, but did that patient have a mutation in exons one to 17? A quick follow-up on EMBARK. What is the status of enrollment? When do we expect that to be completed? Thanks so much. I'll answer the first one, and Louise Rodino-Klapac, you correct me if I'm wrong. The answer on the first one is the child wasn't within the 1 through 17, and this wasn't any innate immune response or anything like that. And then on EMBARK, we said we're gonna complete dosing around the middle of the year. We're on track for that. So things are going quite well there. We'll provide an update to folks once dosing is complete. Our next question comes from Hartaj Singh with OpCo. Your line is open. Hello. I'm Eka dialing in for Hartaj today. Congratulations on the data, and thanks for the question. Our question is about manufacturing. With these data in hand and interactions with the FDA that are ongoing as well, could you comment on your commercial readiness and manufacturing scale-up to potentially meet the demand if you were able to file for an accelerated approval? Thank you. Yeah. Thank you for that. We will be ready. We, you know, scenario plan all the time and, in the event that we could get. As everyone knows, our base case is that EMBARK will be the pathway for our approval, and that remains the case, unless and until we're able to say something different than that. We scenario plan so that we would be prepared to serve the community upon launch, either after EMBARK or earlier if that was possible. The one thing I will say is obviously we'll have a lot of inventory to build, but we'll do that, and we'll be in good shape. We'll now have Ian read an email question. Oh, Ian, you're on mute. Apologies for that. Salveen had trouble getting on, Salveen from Goldman Sachs. Louise, the question was, for the integrated data, how do we reconcile the commercial versus the clinical product in the analysis? Her second question is, has the FDA provided guidance on how to determine propensity matching? Yeah. Good question. For the commercial versus clinical material, what's the beauty of this is that the 9001 dystrophin is the same in our clinical and commercial material. As you can see, we saw consistent results in terms of expression on both. In addition to that, as you also saw, we performed the integrated analysis, but we also performed individual analyses with each study. We saw consistent effect across those studies and then when we integrate the data together. In terms of the guidance on propensity matching, there's multiple guidelines available that we complied with. Some of these include the FDA E10 guidance, as well as the Adaptive Designs for Clinical Trial guidance, as well as DMD and Rare Disease guidance. That's just to name a few. We certainly comply with those, in terms of designing the propensity-score matching. Just to follow up for Louise, Salveen, just so you know, the clinical-commercial process. The clinical material was used in Studies 101 and 102, and then the commercial process material was used in 103. Like what we said, you can easily break it down that way. Our next question comes from Gena Wang with Barclays. Your line is open. Thank you for the question. Yes. Yeah. I'm sorry. I missed it. Okay. Can you hear me now? I'm sorry. I hope. Yeah. I apologize, Gena. Unless I'm alone, I can't hear the question. Apologies for that. Can you hear me now? Yes. Yes. Can you hear me? Okay. Yeah. Okay. Perfect. The question is if I'm getting accelerated, so you know to submit for the accelerated approval, or you know another alternative is a rolling submission. If the timeline, the time FDA will need to make a decision is very close to your phase III trial EMBARK readout. Do you think regardless what path FDA will still you know be under conviction to have you know approved? Yeah. I'm gonna apologize, Gena. I didn't fully get the question. I'm gonna try to deduce what the question was, which is, What I think you were asking, and apologies for not getting it fully, was that, you know, assuming that we got an answer from the FDA that allowed us to submit a BLA, then if the review time for that BLA might be, might run close to the readout for Embark. I think that might be what you're asking about. The short answer is that, if we could file a BLA for accelerated approval, it would provide an enormous opportunity to get this therapy to patients as quickly as possible. You know, we'll see what the FDA's perspective on that is. Once we know, we'll let you all know. The exciting thing about the data today is, you know, while we were very pleased to be able to provide it to the agency and to have discussions, productive discussions with them, we're also very excited about what this means for the powering of EMBARK and the probability of EMBARK, which is our base case. Again, I apologize, Gina, if I completely misunderstood your question. I'm sorry about that. We have another email question. Ian? I'm sorry. I don't see another email question. If you, Ian, look at our chat real quick. This question's from Brian Skorney from Baird. Okay. The question is, Jerry presented three-year data from study 101 last year and included percent predicted 100-meter walk. I think patients were generally in the range of about 50%-70% predicted, and it was noted that natural history would be about 44% at three years. I think natural history comparisons are really helpful, but I also find comparisons to non-DMD subjects helpful too. Can you provide any color on where these patients are sitting relative percent predicted at four years? Just trying to get a handle on not just how these patients are comparing to DMD, but if they're also getting closer to non-DMD controls. Yeah. Thank you for that question. Essentially, the percent predicted is, you know, the correlate of what we showed in terms of we showed a decline in the amount of time that it takes to do that activity. The percent predicted is sort of the inverse of that. You're right, we've seen a consistent improvement in the percent predicted. We don't have the exact number on comparison to natural history, or certainly something that we could do. To your point, these patients are, you know, definitely more approaching a normal control than the natural history of DMD, but I don't have the exact numbers for you today. I mean, the 34 point is the maximum for this scale. I think the normal range in these kids sort of varies from, what, 31 to 34, Louise? We've got kids over 30 in this, so obviously they're doing well. Our next question comes from Brian Abrahams with RBC. Your line is open. Hey there. Thank you for taking my follow-up. Do you expect a clear answer from the FDA on whether the data you have in hand would support accelerated approval? Or are your discussions centered more around exactly what types of data and analyses you might need to provide in a filing and that you'd plan to file regardless, and the decision would really come down to being a review issue as to whether or not this could be approved on an accelerated basis? In the end, I mean, I think everything's a review issue once you file a BLA. We're not gonna get an answer in advance that's definitive. We will get a clear view from the agency, and I suspect on whether it would be wiser for us to file a BLA for accelerated approval now, or whether we should await EMBARK. Obviously, we'll be guided by that. We're not gonna file a BLA unless we have an enormous amount of conviction that we're gonna have a very positive review of that BLA. I think we'll get a relatively definitive view on whether it makes sense to file a BLA or whether we should wait for EMBARK. Our next question comes from Chang Liu with Needham. Your line is open. Chang Liu, your line is open. Sorry, I was on mute. This is Chang for Gail. Thank you for taking our question. Will there be another integrated analysis at two-year mark? If there is, what should we expect from the natural history? It seems intuitive that the trend should go down in the second year, but the external control for 101 is actually increasing. I don't know if we have a planned integrated analysis for year two. The integrated analysis that we did that you saw today was really in support of our discussions with the FDA about the full data set. I think you know, obviously the thing we're most excited about next from a data perspective is the readout EMBARK, which will happen around the middle of next year. Louise, do I have any? Is there anything I'm you know, incorrect about what I just said? No, that's accurate. All I would add is that our, you know, primary endpoint for the study was at one year, and that's obviously for the integrated analysis that at one year, we may choose to do additional analysis of the four to six. But the primary endpoint was one year. There are no further questions. I'd like to turn the call back over to Doug Ingram for any closing remarks. Thank you, Michelle. Thank you all for joining us today. If you don't mind me extemporaneously congratulating my colleague, Dr. Louise Rodino-Klapac. You know, I would remind everyone that Louise is not simply our head of R&D and Chief Scientific Officer, but she along with her colleague, Dr. Jerry Mendell, designed this therapy and painstakingly tested it and optimized it over many years. This is an enormously important day for Duchenne, and I frankly think an important day for Louise as well and Sarepta. Congratulations on that, Louise. We look forward to providing additional updates across the year as we achieve milestones. As it relates specifically to SRP-9001, this includes the outcome of our discussions with the FDA, so we'll certainly provide you an update on that, and also on the completion of dosing for EMBARK, which we will update on that as well. Until then, I would ask everyone to have a good day and be well. This concludes the conference call. You may now disconnect.