Good morning, ladies and gentlemen, and welcome to Sarepta Therapeutics Program Update Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will be given at that time. We ask that you please limit yourselves to one question. 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. Thanks everyone for joining us this morning. Next slide. Before we begin, I'll remind you to please look to our public filings for a discussion of the various risks and uncertainties that's associated with making forward-looking statements or predictions about the future. Next slide. We are very pleased to report the results from MOMENTUM Part B, the study examining the expression and safety of SRP-5051, our next-generation peptide conjugated PMO therapy for the treatment of Duchenne patients amenable to exon 51 skipping. As you'll see, SRP-5051, if successful, could be a significant advancement over the current gold standard oligonucleotide therapy for Duchenne. And with that, I will pass the call to Dr. Louise Rodino-Klapac, who will review the study results. I would also note that our Chief Medical Officer, Dr. Jake Elkins, is available as necessary for Q&A today as well. With that, Louise? Thank you, Doug. It's a pleasure to be here today. Next slide, please. SRP-5051 is our lead RNA-based PPMO therapy in development to treat Duchenne patients amenable to exon 51 skipping. Duchenne is caused by a genetic mutation in the dystrophin gene. Most commonly, one or more exons or parts of the gene are missing, causing errors in the instructions for making dystrophin. Sarepta's PMO platform uses a phosphorodiamidate morpholino backbone chemistry that precisely targets a specific sequence of a pre-messenger RNA that enables the translation of an internally truncated, yet functional dystrophin protein. Sarepta is currently serving the Duchenne community with three approved products from our PMO platform: EXONDYS 51 for patients amenable to skipping exon 51, VYONDYS 53 for patients amenable to skipping exon 53, and AMONDYS 45 for patients amenable to skipping exon 45. All three of these drugs have consistently shown increased exon skipping and dystrophin production in patients. Peptide phosphorodiamidate morpholino oligomers, or PPMOs, are Sarepta's proprietary next-generation PMO-based therapies and development, and are specifically designed to increase tissue penetration. Next slide, please. To remind you, MOMENTUM is a global clinical study evaluating SRP-5051 in patients with Duchenne who are amenable to exon 51 skipping. The study evaluated dystrophin protein levels in skeletal muscle tissue at two dose levels, a high dose of approximately 30 mg/ kg and a low dose of approximately 20 mg/ kg. Safety and tolerability were also assessed. Part B of the study enrolled 40 new patients from the ages of 8- 21 in the United States, Canada, and the European Union. Approximately half the patients who participated in the study were ambulant, and the other half were non-ambulant. Patients who were dosed in Part A and met the entrance criteria also participated in Part B. Throughout the study, we continued to administer prophylactic magnesium supplementation and/or adjust the dose to manage hypomagnesemia. Next slide, please. In the first four weeks of the study, patients are monitored and receive a loading dose. They therefore experience 24 weeks of dosing at the relevant therapeutic level. Now to the clinical results for our next generation PPMO, SRP-5051. We are quite pleased to see a significant increase in dystrophin in both treated groups. We observed a 5.17% dystrophin production in the high dose group. This is over 12.2 times more dystrophin than eteplirsen. We believe this greater production of dystrophin will also translate into improved clinical results for patients. Further, we continue to believe that we will observe accumulation of expression over time. We've observed the biggest increase in expression from 48 weeks to 96 weeks of treatment with PMO. Next slide, please. Importantly, the data represented here shows that similar levels of expression were observed in both non-ambulatory and ambulatory patients. This reinforces that all patients with Duchenne can potentially benefit from dystrophin restorative therapies. Next slide, please. SRP-5051, administered monthly, showed mean exon skipping of 11.11% at the high dose at week 28. Further, the results represent a 24.6-fold increase versus eteplirsen. Next slide, please. Now looking at immunofluorescence results. SRP-5051 demonstrated a mean of 50.68% dystrophin positive fibers, or PDPF, at week 28 and a 4.6-fold increase versus eteplirsen. Next slide, please. Now to the safety results. Next slide. It's important to note that mild to moderate hypomagnesemia and/or hypokalemia is very common and is generally asymptomatic or associated with only mild symptoms, stable, or resolves with supplementation. Hypomagnesemia, hypokalemia resolved with standard intervention and was not associated with any other clinically significant adverse events. With regards to estimated glomerular filtration rate, or eGFR, declines have been asymptomatic, non-serious, and not associated with any other biomarker abnormalities of tubular injury. Several cases have resumed dosing. Cases have occurred in non-older non-ambulatory patients where causality is uncertain, as some cases may be caused by background rate and/or other confounding factors, such as concomitant medications. Close monitoring continues. Next slide, please. We are pleased to have achieved the study's primary endpoint and to demonstrate dystrophin expression at both the low and high doses and achieve 5.17% dystrophin expression at the high dose at 28 weeks. The safety profile seen in the study is consistent with the known side effects profile of SRP-5051. Throughout MOMENTUM Part B, we continued to administer prophylactic magnesium supplementation and/or adjust the dose to manage hypomagnesemia. Importantly, no treatment-related discontinuations occurred in this study. Based on these results, we are requesting a pre-NDA meeting with FDA. We anticipate this meeting will occur in the third quarter of 2024. Sarepta's role is positively impacting the lives of individuals with Duchenne continues, ensuring patients can access meaningful treatments to manage this aggressive, debilitating disease. Next slide, please. Thank you for your attention. I'll now turn the call back over to Doug. Thank you, Dr. Rodino-Klapac. Michelle, let's open the call for questions and answers. Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. As a reminder, we ask that you limit yourself to one question, please. Our first question comes from Gena Wang with Barclays. Your line is open. Thank you for taking my questions. I have two. You know, one is regarding the efficacy part, the protein level. When we compare to the Part A, at the shorter follow-up, I think at week 12, we did see, like, protein expression level was at 6.55%. Here we have a longer follow-up, update. The protein level, seems like a little bit lower than the Part A. So wondering, you know, what could be the reason there? And the second question is, regarding the safety. It seems like there is a, a very high rate of, the hypo, magnesium, hypomagnesemia, so and, and also have some hypokalemia. Based on the current safety profile, do you think that that will be sufficient for approval, or will be some additional, say, those findings, study that need to be done? Thank you very much for your question. As to relating to the first question, I think as Louise will explain to you, and I won't jump on her lines. The results of this study are at least in the hunt of what we saw previously, and in many regards, may be better than what we saw last time. And then, so I'll let Louise comment on that, and then Louise can comment on the safety profile and the positive risk-benefit. Sure. I think I mean, first of all, I'd just say that we're extremely pleased with these results of dystrophin expression. As we know from the literature, 5% expression has a significant improvement in the trajectory of patients. In terms of the results from Part A and Part B, I'd say Part B is entirely consistent, if not better, in terms of the fold increase that we saw in Part A, in which we saw a small number of patients. This is a much larger sample size. Also the potential to see increases over time continues. As we have shown previously with PMO, we saw a large, almost threefold increase between the 48 weeks and 96 weeks. About a quarter of the patients already are seeing about 10% expression in Part B. So just to summarize, we're thrilled with the results we're seeing. This is a large data set with dystrophin levels that are extremely beneficial to patients. In terms of safety, the hypomagnesemia is well controlled with the prophylactic supplementation, and I'll ask Dr. Elkins if he wants to add anything regarding the monitoring and management of the hypomagnesemia. Yeah, thanks. And then I'll just add that, you know, the monitoring is something that, we're doing in the study, and it's successful. We haven't had people that need to come off the therapy. So, you know, we think that the events of hypomagnesemia and hypokalemia are, you know, lab abnormalities that, we need to check for and address with the supplementation, but this has been adequate to, you know, control these events and, allowing people to remain on the therapy. Thank you. Our next question comes from- But before I go, before you go on, Michelle, just to really put a a exclamation point on what Louise noted about dystrophin production. You should know the amount of dystrophin is important. The fold change is extraordinarily important because baseline characteristics can differ. When we look at this study versus our prior study, we saw in the prior one, it was brilliant. We saw in part A, we saw 18 times exon skipping and 18-fold increase in dystrophin over eteplirsen. But in this study, we see a 24-fold increase in exon skipping and a 12 times increase in dystrophin. And one of the things that we have said is that, you know, our history shows and the evidence for these PMOs show that the dystrophin builds over time. Already in this study, which was only 24 weeks, essentially on actual therapy, a quarter of these kids were already over 10%. So we're very excited about the amount of dystrophin that's being made here. This is, at this point, at least, really is unprecedented for, oligonucleotide. Sorry, Michelle. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Good morning. Thanks for taking my question. Just to follow up to the earlier point, how difficult is it to manage the hypomagnesemia in practice here? And then secondly, just speak to how you think the long strategy would play out with this drug and who the adopters might be in the context of coexistence with your other assets. Thank you. I'll let Louise and Dr. Elkins answer the monitoring issue, and then we'll talk about where this fits in the paradigm thereafter. I'll answer that. Louise? Yeah. The hypomagnesemia is very routine to monitor and to administer the prophylactic supplementation. It's become a routine part, and it's very simple for the PIs and the families to manage. But Dr. Elkins, if you want to add anything to that. Yeah, I mean, the prophylactic dose that we put the patients on is well tolerated. We're generally targeting, you know, one lab draw in between the monthly doses as part of the monitoring. So. And this is something that, you know, has been very manageable for the physicians. And, you know, the thing that we hear from them is that increasing levels of dystrophin is very important, and this is their main goal. And, you know, the monitoring regimen is something that they get used to it and that they find that this is easy to manage in the clinic. Now, on your other question, so the question, as I understand it, is essentially, where will this fit in in the entire paradigm of the treatment of children with Duchenne muscular dystrophy? Well, we've pondered this, obviously, as you know, for a long time. There are three big pieces of information that one needs to really complete an analysis like this. The first one we're announcing today, which is, what do the results look like from a next-generation peptide conjugated PMO, SRP-5051? As you've heard from Louise and others, we think it looks fabulous. We're seeing what would be a significant advancement over what is currently the gold standard for the treatment of children with exon 51 amenable Duchenne in the form of oligonucleotide. So we're really excited about that. We think that, you know, obviously, the benefit risk, we think is positive on this, so we're very excited. There are two other pieces of information that we need. The next thing we're going to need, obviously, is to know what the, the label is gonna look like for ELEVIDYS. As everyone knows, it's not gonna be a subject of our discussion today, but we're in the midst of a BLA supplement, with the goal of expanding, hopefully maximally, the label for ELEVIDYS. And that, that label expansion will play a role in where SRP-5051 would, would fit into the larger paradigm, and we're, of course, we're working on that. Then the other big piece of information that we need is the FDA's perspective on all of this, and what is the pathway forward that would relate to timing and the like. And so we need all of those three pieces of information. We'll have that last piece of information in the third quarter of this year, when we're gonna do the entire analysis and look at exactly where SRP-5051 fits into the broader paradigm. And, you know, certainly, we would suspect before the end of this year, we'll come back, and we'll chat about that. But what we have today is the first piece, and in many ways, probably the most important piece, which is: What does this therapy look like in children with Duchenne muscular dystrophy who are exon 51 amenable? From our perspective, we have a safety profile that's manageable and monitorable and an amount of dystrophin that is in all regards unprecedented, at least as relates to a non-gene therapy oligonucleotide. So we're very excited about where we are today. Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open. Hi there. Good morning. Thanks for taking my question. I guess, how much do we know at this point about the pathophysiology of the hypomagnesemia? Is that something, we have a better understanding of now that there's more data? And then, I guess, on a related note- ... Can you maybe contextualize the GFR reductions, the potential relationship that had to the electrolyte changes that we're seeing? And are there any lab measures that you've done or can do to further tease out the degree of potential relationship that might have to SRP-5051? Thanks. Good question. Louise? Yeah, I'll start with addressing the pathophysiology. So we do know that there is a transient competition for absorption in the reabsorption in the kidney, and that's likely from our early studies leading to the transient hypomagnesemia. But with regards to the eGFR monitoring and other testing, I'm going to ask Dr. Elkins to address that. Yeah. Okay. So, I mean, with regard to the GFR monitoring, you know, we do measure a number of renal biomarkers, other issues, other urinalysis tests as part of the monitoring in the study. And we're not seeing any association of either the hypomagnesemia or these GFR changes with those biomarkers. So, you know, this is something, you know, that is seen primarily in older patients. As you know, some of them have start with high levels of GFR, and they come back, you know, even with the declines, can still be in the normal range. So, you know, some of this may represent a regression to the mean that we see over time with the monitoring. You know, we review with our experts on these events. So it's something we're continuing to investigate and monitor closely in the study. But I think the important thing for now is that we're not seeing an association with them, with any other markers of nephrotoxicity. They haven't been considered serious events by the investigator. They haven't been associated with any clinical symptomatology. Thank you. Our next question comes from Gil Blum with Needham and Company. Your line is open. Good morning, and congrats on the results, and thank you for taking our question. Just a quick one for me. It looks like a pretty big jump in activity from 20mg- 30mg. Do you find this surprising? Thank you. Louise? Based on our non-clinical studies and our previous studies of Part A, we weren't surprised to see the difference between the 20 and 30 mg. It's just based on the essential curve of dystrophin production based on the tissue concentration of the PPMO. Well, one of the things that is exciting, and I do agree with you, Gil, it's you really get a significant step up with the 30 mg. But what is great is that at the lower dose, you're still seeing a significant improvement over the current gold standard. You're still seeing 4.3 times greater dystrophin production and almost five times greater exon skipping. So from the, you know, all things being equal, we would have been pleased with the low dose. We're very excited about what we see when we move to what is approximately 30mg/ kg. Thank you. Our next question comes from Colin Bristow with UBS. Your line is open. Hey, good morning, and congrats on the data. I was wondering if you could talk about the timing of the hypomagnesemia and hypokalemia, you know, relative to the dosing. And then within the patients, did you see these electrolyte changes moderate over time? And just in relation to this, can you remind me what was the frequency of EKG monitoring, and whether you observed any EKG changes related to these electrolyte disturbances? Yeah, Louise? Dr. Elkins, would you like to address that in terms of the timing of the hypomagnesemia? Yeah, I mean, in general, what we see is that, you know, when people first start out on the treatment, the, you know, there's more adjustment of the prophylactic regimen to, you know, keep the electrolytes within tolerable ranges. You know, this is. And over time, this looks to be successful, right? So, you know, we do think that, you know, over time, that the monitoring, the frequency is gonna be something that would become less frequent. You know, we don't see any EKG. We haven't associated these events with EKG changes. You know, there's no regular EKG monitoring that's required. Whenever there is an electrolyte abnormality, our PIs are just, you know, managing it according to standard of care, with, you know, the standard of care repletion, and the patients respond quickly to that. So, yeah, they haven't been, they haven't been associated with clinical events, and that's something that, we think, you know, the main thing is finding that initial adjustment and getting people on the right prophylactic dose of magnesium, in order to manage them over time. Thank you. Our next question comes from Ritu Baral with TD Cowen. Your line is open. Ritu Baral, your line is open. Good morning, guys. Thanks for taking the question. Doug, I'm gonna ask you the same question I asked you in January. Just given ELEVIDYS path forward and potential label expansion, including potential full approval, where do you think the probability stands that these exon skippers still have an accelerated path forward on dystrophin expression? You know, how will it- how could it work? I know you have no clarity right now, but how could it work- Yeah. given ambulatory versus nonambulatory and FDA's understanding of unmet medical need in the event of a full approval, for some population in ELEVIDYS? Thanks. Yeah. Well, I, I think there's maybe two subtle questions in there. Let me, let me make sure. If one possible question is just, is the accelerated approval pathway more or less likely in the face of ELEVIDYS? I really don't, on the face of it, see a difference there. I think this will, as it stands, stand on its own. Then the second question is, where does it fit into the broader paradigm? We have said for a long time two things that are at tension with one another. One thing is that there will be cannibalization of the PMO over time to the extent there is success with ELEVIDYS, one could expect that. We've also said that we truly believe there is an opportunity for both of these modalities to exist, and benefit patients. I think that... Well, to your point, I don't have yet clarity, and we'll have more clarity this year. The probability of that, I think, increases with great results. And, you know, again, to editorialize a bit, I think these are great results. I think if this was equivocal, then you might say, maybe there isn't a path for the next generation, PMO, peptide conjugated PMO, in the face of ELEVIDYS. But at least this, you know, is really fantastic results. Just to characterize this, remember, if you go back to the Aartsma-Rus paper, which is kind of the current paper that really describes what it means for different levels of dystrophin, 5% is a bellwether amount of dystrophin that really correlates with a significant change in life expectancy, ambulatory status, and the like, so that's exciting. But with all of that said, we have to do two more things. We have to see what the label for ELEVIDYS will look like. If, for instance, you know, we didn't get the entire population or we had, you know, some other, approval for the nonambulatory population, that may impact this opportunity. We have to see what the FDA says about all of this and what the pathway forward for this looks like, and that will reflect, you know, not only the amount of effort that goes into it, but the probability of success, the timing of it, and that'll play into this. And then we'll take all of that information, plus the information that we're disclosing today. We'll do that analytic and determine where 5051 fits into the paradigm for the treatment of Duchenne patients, and we'll come back, and we'll have a discussion about that in the back half of this year. Thank you. Our next question comes from Danielle Brill with Raymond James. Your line is open. Hi, guys. Good morning. Thanks for the question. Quick clarification from me. I wanted to know how many patients required dose interruptions in the trial, and if any were dosed per protocol at 30 mg/ kg every four weeks. Thanks so much. Yeah, Louise? Just the second part of your question was, how many patients were in the 30 mg/ kg? Was that the question? I believe so. That's about half of the patients. Jake, do you want to take the first part of the question about any potential dose interruptions? Yes. So I mean, in general, we've been successful in, you know, managing the, patients with either, you know, a transient dose reduction, or, and sometimes, you know, missing one dose before, starting on the treatment. This is relatively infrequent in the study. It's approximately 10%, that maybe have, you know, go through this regimen of temporary reduction or, you know, missing, a single monthly dose. But then, you know, as we've described, these patients are then successful at re-escalating, and getting back on the regular regimen of dosing. So, you know, again, it's something that we monitor, especially as we're getting people on their initial prophylaxis, and that it seems to be stable, and, we're successful keeping people on their regimen over time. Hey, Ian, just one thing to quickly add, because I think in the question it sounded like the question was really around, did patients stay on the 30 mg/ kg dose? And obviously, if you look at the data and see the differential between the expression between the 20 and the 30, it's very clear that the vast majority of patients on the 30 remained on the 30. Thank you. Our next question comes from Nina Grygorenko with Deutsche Bank. Your line is open. Hey, guys. Thanks for taking my question, and congrats on the update. So I know that you mentioned earlier that the expression levels are increasing over time, but I'm just curious if you can talk a little bit about what that curve over time looks like and when you expect expression levels to start to plateau. And I really just want to understand what additional data you could have by the time you actually have that pre-NDA meeting in Q3. Thanks. ... I'll turn that over to Louise. I don't think we'll have additional data by the time we speak to the FDA. We have a lot of data now. One of the things I did note is that, you know, a quarter of the kids are already over 10%. But the 5%, just so we're clear, is not only much greater, to my knowledge, than any clinical data for an oligonucleotide before, but is, if you look at the literature, a bellwether amount of dystrophin for a transformative effect. So with that, Louise? Yeah. In terms of accumulation, we know that dystrophin accumulates over time from both our non-clinical studies and additional clinical studies. So for example, with our PMO studies, we were able to monitor dystrophin over time, and between 48 weeks, so one year and two years, we saw a threefold increase in the amount of dystrophin. So as more fibers are protected, you get accumulation of dystrophin, which, you know, it leads to increases in dystrophin over time. Michelle? Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open. Hi, thanks very much. I was wondering, it sounds like you're pretty comfortable with the ability to manage the hypomagnesemia and hypokalemia, but, could you just talk a little bit more about the seven serious events? Were all of the hypokalemia issues related to patients with hypomagnesemia? And, have you learned any more through undertaking MOMENTUM in the prior study? Are you learning more about your ability to manage this? And, you know, how strong of a case do you think that you can make to the FDA? And do you have robust data to show, you know, throughout your experience now in these, in the study, Part A and B, that, you know, you have a, you know, a pretty confident way of helping clinicians manage these issues? Thank you. Okay. Go ahead. Yeah. I'll just make a couple of comments, and I'll turn it to Jake. Just generally, the hypomagnesemia, the serious events were based on the levels of hypomagnesemia, not any clinical sequelae. In terms of the management, you know, as you mentioned, there was learning in the beginning until PIs figured out how to appropriately manage to be on the right dose and the frequency of that dosing, but they're quite comfortable with that now. So Jake, if you wanna address the part about the events, the hypomagnesemia versus the hypokalemia, the relatedness. Yeah, just echo what you said, that the serious events is based more on the level. It's they, they haven't been associated with clinical symptoms. You know, in those events, frequently, we would pick. You know, the PIs would use an IV repletion to get people back up. But, you know, the events respond quickly to that, and they off. You know, these are not patients where they frequently recur. So many of these patients, they get the repletion, they go back on the treatment, and it doesn't seem to be a problem going forward. So yeah, I think we have learned about how to manage these better, in terms of the, mainly the starting prophylactic dose for, you know, giving the magnesium supplementation. We think that this has been more successful at reducing those events where, you know, the lab abnormalities are more prominent. So, this is something that we're implementing going forward, and we think we understand, and the PIs have become more, you know, are more comfortable with, you know, how to manage the repletion, the prophylaxis over time. Thank you. Our next question comes from Anupam Rama with JP Morgan. Your line is open. Hi, guys. This is Priyanka Anand from Anupam Rama. Just a quick question from us: What are the gating factors to a filing in Q3, and do you need any additional safety follow-up? Thanks. I'm gonna turn this over to Louise. The one thing I'll say, the biggest gate is to have the meeting, the pre-NDA meeting with the agency and have a discussion with the agency and obtain their perspective on the pathway forward. Beyond that, Louise? No, that's exactly right. So we request the meeting. We'll continue to provide safety data as part of that filing. The expression data will be consistent with what we have now, but we'll request the meeting and, you know, provide the safety data, but nothing else particularly gating. Thank you. Our next question comes from David Hong with Citigroup. Your line is open. Hi. Thanks for the update and taking my question. I just wanted to ask in regards to this data, do you envision any type of path forward, with European or other ex-US regulators? ... for 50, 51? We're evaluating that along the way. So we're sort of prioritizing the U.S. filing right now because we're gonna have an NDA, a pre-NDA meeting with the agency in the third quarter. And then the team is evaluating what the implications of this is for an ex-U.S. approach. Thank you. Our next question comes from Tim Lugo with William Blair. Your line is open. Thanks for the question. Of the 20 patients in part B, how many of them have expressed interest in gene therapy if the, obviously, if the label is expanded? Louise, do you have any information? I doubt that we have information like that from these patients. I do not, no. Yeah. Thank you. Our next question comes from Kristen Kluska with Cantor Fitzgerald. Your line is open. Hi, good morning. This is Jason Bouvier on for Kristen. Thank you for taking our question. Just going back to Dystrophin expression. In the past, you've talked about around 10% Dystrophin expression being possible with chronic dosing based on the preclinical models. Can you talk a little bit about how you're thinking about these results in the context of the preclinical models? Thank you. Yeah, these results, you know, I really wanna be clear. These results are really gratifying to us. Just, just to remember, again, we're looking at a very short timeframe, 24 weeks on therapy. And if you compare part B to part A, and you look at it as fold change from baseline, which is a very fair way to look at it, in addition to the aggregate, what you see is not only is, does it appear to be generally consistent with what we saw before, but actually in fold change, it's significantly greater. You saw with the target dose or the high dose, you see, you know, 24 times eteplirsen in a fold change. So really, think about that. That's, it's significant advancement over the current gold standard. And I would remind you, give a little pitch for the PMOs, eteplirsen or EXONDYS is the gold standard, for the treatment of Duchenne muscular dystrophy using a chronic oligonucleotide. And in fact, the real world evidence on that has looked just fantastic. We've presented that in the past. Over the last couple of years, you see a significant attenuation of loss of ambulation. You see from a hazard ratio perspective, a significant benefit on, you know, life expectancy, on time out of the hospital, on emergency room visits, fractures and the like. And this is multiples greater than that. And then if you compare B to A, this is, you know, almost double what we saw in fold change from A. So we're very excited about these results. One of the things I said before is, you know, while this will build over time, a quarter of the children on the high dose are already at 10%. We're very excited about the results that we have here. Thank you. Our next question comes from Brian Skorney with Baird. Your line is open. Hey, thank you for taking the questions. I guess my first one is, given the profound changes you've seen with all 11 different CK measurements, I'm just wondering if you looked at CK here, and if there was any, any change, for these patients given the robust expression? And then for the patients with the, with the eGFR declines, did these events all coincide with, hypomagnesemia SAEs? And maybe what is the maximum decline in eGFR seen in the lowest eGFR, achieved in the study? Yeah, Louise? Yeah. So as far as CK, we don't have that data available yet. As far as the eGFR, it was not, we did not see a correlation with the hypomagnesemia events. Jake, do you wanna add anything to that regarding the eGFR question? Yeah, I mean, right, there, there isn't any relationship between the hypomagnesemia and the eGFR declines. The eGFR declines are not- or, or the hypomagnesemia aren't associated with the other renal biomarkers that we're measuring, the urinalysis testing that we're doing. And so, yeah, I mean, you know, the number of events is small. The protocol- our protocol right now requires, you know, treatment suspension if there's a 30% decline in the eGFR. And so that's something, that's a level that we, you know, are monitoring for. But other side, you know, many of these cases, they could be starting out at a high level, they decline, they, after, you know, time, these events can come back to normal. And so it's something, you know, it's still... The eGFR is something in this population that does fluctuate. Different medications that are being used can alter the eGFR. So, you know, the key finding for us so far is that the events haven't been symptomatic. They haven't required any other types of intervention, and many of these patients have successfully restarted the dosing, and they haven't recurred. Thank you. Our next question comes from Hartaj Singh with Oppenheimer. Your line is open. Great. Good morning, everybody, and thank you for the question. You know, I saw on the, on your press release that you treated boys from eight to about 21 years old. Can you just give any color on, you know, maybe the boys that are a little bit older than what we're, you know, have seen on PMO therapy and the gene therapy and, you know, whether they're ambulatory or non-ambulatory. And then what were some of the, you know, the efficacy you saw there and any safety effects that might have been more in the older boys? Thank you. I'll turn this over to Louise to talk about, you know, the safety experience. From an efficacy perspective, you will have seen when Louise provided her presentation, that you're seeing a significant amount of dystrophin, both in the non-ambulatory and ambulatory boys, as one would expect. So this should be beneficial across all ages, which is, of course, what we expect with any dystrophin-producing modality, whether it's an oligonucleotide or a gene therapy. But with that said, Louise. Yeah, I think, you know, we're pleased with the way all patients responded and the consistency between non-ambulatory and ambulatory. With regards to safety, the majority of the events were independent of status. As Jake mentioned, with eGFR, we did see those more in the non-ambulatory patients, but that was more of the exception to the safety. But overall, the entire pocket's benefit risk. Thank you. Our next question comes from Andreas Argyrides with Wedbush Securities. Your line is open. Yeah, good morning, and thanks for taking our questions. So, the threshold amount of dystrophin, and you said this in the past, at one year is around 10%. Do you expect or continue to expect to get to those levels? And how would that and these results today and those expectations play into your thoughts around potentially bringing this program to market with ELEVIDYS available? And then, if you do decide to bring it forward, what additional data do you think you need to show payers to get on board with the 51? Thanks. Well, there's a lot, there's a lot of analysis that has to go into that. We're gonna do a lot of that analysis over the course of this year. We have to get informed both by what the FDA's perspective is, as well as what the ELEVIDYS label will ultimately look like. Hopefully, we'll know that in the not-too-distant future this year, and then we'll be able to make all of the analysis. One of the things I said earlier was that we have seen about a quarter of the kids get over 10%. I wanna be clear, that's just a prediction about dystrophin building over time. The results we're seeing today at these levels, let us assume that this was the level that you received from this therapy. I wanna be clear, this is an unprecedented amount of dystrophin for an oligonucleotide. And again, I would point people to, for instance, the Amthor paper in 2018 that describes what 5% dystrophin can mean for patients in a, in, you know, delay and loss of ambulation, in predicted life expectancy and the like. And then I would compare it against what we have with our current PMOs today, which are already doing an enormous amount of good for patients, as well. So you know, we're very excited about the results we have today. We do have to get additional information. We have to find out what the ELEVIDYS label will look like and the timing of that. We have to talk to the FDA and discuss with them the path forward and really be informed by the division. And then based on all of that, we're going to do an objective analysis and determine where SRP-5051 fits in in the armamentarium, therapies intended to benefit kids with Duchenne muscular dystrophy who are in need of therapies like this and ELEVIDYS. Thank you. There are no further questions at this time. All right. Well, thank you everyone for joining us today. I do wanna linger for a moment and thank the families and the children who participated in this study. They've done a lot of good, not only for their families, but for the broader Duchenne community and the advancement of the science and therapies like SRP-5051. I wanna give an enormous amount of thank you to our clinical investigators who have been committed to this program and thank the internal team who've done just fantastic work getting us to where we are today. And of course, they've got a lot of work yet to do, and so I wanna really commend them for this effort because I think it could be extraordinarily important. We're very excited about the results that we have today. We're looking forward to what we have to do over the course of this year. As I've said a few times today, I'll repeat again, we need to take these results, we need to share it with the FDA. We need to talk to our division and get their perspective on it in the form of a pre-NDA meeting, which we will have in the third quarter. We need to complete our discussions with the FDA on the ELEVIDYS label and in its expansion, and then, consider where this therapy lies in the full armamentarium of therapies that can benefit children with Duchenne muscular dystrophy. We will complete that entire objective analysis with all of that information available to us in the very back half of this year. And then, of course, I look forward with the team to reporting back and talking about the path forward for SRP-5051. And with that, thank you all, and have a wonderful day. Ladies and gentlemen, thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, have a great day.