Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics SRP-5051 program update conference call. After speakers' remarks, we'll be doing a question- and- answer session. 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, Victor, and thank you all for joining us today as we discuss the clinical hold in the United States for screening and dosing and MOMENTUM, our trial for SRP-5051, our PPMO candidate to treat Duchenne patients amenable to exon 51 skipping. Let me remind you that we may be making some forward-looking statements today. As we do those, please refer to our public filings for the various risks and uncertainties that come whenever one attempts to make predictions about the future. Now, let me make a few points in advance of Dr. Louise Rodino-Klapac providing real detail on this. First, as you've seen, after a serious adverse event of hypomagnesemia in the trial, the FDA is requesting information on all cases of hypomagnesemia, including a handful of non-serious Grade 2 cases, to assess the adequacy of the risk mitigation and safety monitoring program that we have. Our first priority, as you can well imagine, is patient safety and well-being. We are gonna work very diligently, and we intend to rapidly respond to the FDA's request for additional information. We are confident that we can provide clarifying information to satisfy the FDA's request in the next few days and to resume dosing in the U.S. very expeditiously. The study remains ongoing outside of the United States, and we remain on track to complete dosing in the second half of this year, as previously guided. With that, let me turn the call over to our Head of Research and Development and our Chief Scientific Officer, Dr. Louise Rodino-Klapac. Louise? Thank you, Doug. Good afternoon. Today, we announce that the U.S. Food and Drug Administration has placed a clinical hold on SRP-5051, vesleteplirsen, our next-generation peptide conjugated phosphorodiamidate morpholino oligomer, or PPMO, to treat patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. The hold in Part B of study 5051-201, also known as MOMENTUM, follows a serious adverse event of hypomagnesemia. FDA is requesting information on all cases of hypomagnesemia, including a small number of non-serious Grade 2 cases, to assess the adequacy of risk mitigation and safety monitoring plan. I'll take you through the events and how we plan on addressing this. Recall, MOMENTUM is a phase II multi-arm ascending dose study of SRP-5051 infused monthly and will assess the dystrophin protein levels in skeletal muscle tissue following SRP-5051 treatment. The study is designed to enroll up to 60 participants, both ambulant and non-ambulant, between the ages of seven to 21 at sites in the U.S., Canada, and the European Union, to assess safety and tolerability. We have enrolled approximately 50% of the trial to date. The hypomagnesemia was identified through lab tests conducted as part of the monitoring outlined in the protocol of a MOMENTUM study and is similar to previously observed cases of hypomagnesemia in clinical trials of SRP-5051. The protocol for Part B of MOMENTUM includes prophylactic magnesium supplementation and monitoring of magnesium levels. Magnesium levels improved or returned to normal following additional supplementation. We believe that the SRP-5051 may transiently interfere with magnesium reabsorption by the kidney. Importantly, we have not seen worsening of the hypomagnesemia over time or evidence of acute or chronic renal damage or evidence of persistent renal tubular injury associated with the hypomagnesemia. Furthermore, the cases of hypomagnesemia have improved or resolved while patients remain on treatment and do not appear to worsen over time. The SAE occurred in one patient eight days after randomization to the high dose. He presented with Grade 3 hypomagnesemia along with Grade 4 hypokalemia, or low potassium, and experienced mild to moderate tingling of extremities and muscular cramps. Without the need for hospitalization, he was given an IV bolus of magnesium and discharged on increased oral magnesium and potassium. Symptoms resolved in three days, and his magnesium levels have returned to normal. There was no evidence of complications suggestive of renal tubular injury, renal insufficiency, or changes in ECG. There are additional cases of Grade 2 hypomagnesemia that were mostly mild and asymptomatic and resolved with increased oral magnesium. Our hypomagnesemia monitoring and management plan has effectively decreased the number of significant hypomagnesemia cases compared to our experience in previous studies. As a reminder, we observed that 20% of patients had Grade 3 or 4 hypomagnesemia in Study 5051- 102 and MOMENTUM Part A, whereas in MOMENTUM Part B, we had a single grade three case and no grade four cases, which represents less than 5% of treated patients. The hypomagnesemia observed in SRP-5051 is dose-dependent. In order to further manage this, the Safety Review Committee has proposed modifications to the criteria for dose escalation. If a patient experiences grade two hypomagnesemia, they will be randomized to the low dose arm. Both the low dose and high dose are predicted to be therapeutic based on the results from MOMENTUM Part A. While we take any adverse event seriously, we remain confident in the benefit risk profile for SRP-5051. Results from Part A of the MOMENTUM study found that after 12 weeks, 30 mg per kg of SRP-5051 dosed monthly resulted in 18 times the exon skipping and eight times the dystrophin production of vesleteplirsen, which was dosed weekly for 24 weeks. The Safety Review Committee voted to continue dosing, concluding that the risk-benefit profile is unchanged and remains acceptable in the context of this devastating disease. The risk of hypomagnesemia continues to be monitorable and manageable. There's no evidence of acute kidney injury, and we continue to undertake and enhance our early detection and prevention strategies. The study is ongoing. Globally, we have enrolled approximately half of the planned patients in Part B of MOMENTUM, and we remain on track to complete enrollment by the end of the year. We look forward to responding to the FDA's request in the next few days and working with the agency to re-commence screening and dosing for MOMENTUM Part B in the U.S. as soon as possible. I'll turn the call back to Doug for a brief Q&A. Thank you. Thanks, Louise. Victor, let's open the call for questions and answers. Sure. As a reminder to ask a question, you will need to press star one on your telephone, and to withdraw your question, just press the pound. Sorry. Just press the pound key. Please limit yourself to one question. Once again, that's star one for questions. One moment for questions. Our first question will come from the line of Brian Abrahams from RBC Capital Markets. Your line is open. Hey, guys. Thanks so much for taking my question and for hosting this call. Can you talk about, I guess, the type of management and preventative plan you might expect in kind of a real-world setting, commercially, as you sort of think about, you know, how to put patients on the right doses. Any risk factors there? Then, I guess just as a corollary to that, just wondering how to think about the overall kind of trial integrity if patients do end up missing doses, how to manage through that if most of these patients are being enrolled in the U.S. or outside the U.S. at this point. Thanks. Sure. Louise, do you wanna take that? Sure. As far as the real-world setting, that will certainly be informed after the experience from our trial. Patients are on a daily supplement of magnesium and work with the investigator. Increases need to be made. We'll certainly take that into account, and that will advise our management in the real-world setting, if that occurs. As far as the second part of the question. Sorry, could you repeat the second question? Just trial integrity. If this takes you know a little bit of time to work through this process with the FDA, what does it mean in terms of patients missing doses and overall trial conduct, data interpretability? We're currently enrolling outside of the U.S., and those patients are going through the protocol as planned. Certainly, in terms of the primary endpoint for the study being expression, we've enrolled over half the study, and we don't need a large number of patients to meet that primary endpoint in terms of expression. Certainly, these patients that have to be paused dosing in the U.S. would not be included in that analysis. We're working diligently to resolve this with the FDA very quickly. Thank you. Our next question will come from the line of Gena Wang from Barclays. Your line is open. Thank you for taking my question. Maybe if you can walk us through in detail what is the current risk mitigation and what additional you could do, for the next step and how long does that take, you think that will resolve this issue? Okay. Before I hand it over to Louise, just two things. Remember, the two things to consider is the whether this is monitorable and then is it manageable. On the monitoring side, I think we've shown quite directly that it's very monitorable. The case that we found was found, I think, at the time, completely asymptomatically through the monitoring program and, you know, looking for magnesium levels. On the manageability side, I think generally speaking, you can see that it is generally working very well. You know, it was, like, less than 5% of children that had this serious adverse event, obviously. Beyond that, I think Louise has some additional mitigation aspects to the protocol that we're gonna propose. Louise? I agree. Our monitoring has been working as intended in cases where we've had Grade 2s. The increased oral supplementation has worked well to restore magnesium levels at a single SAE, IV magnesium with supplementation also returning the levels to normal. Certainly, when we met as a safety review committee, the analysis was that if we do have these patients that might be more sensitive, when we do reach Grade 2, we would not randomize them to the high dose and keep them on the low dose. That was the recommendation from the SRC or the Safety Review Committee. Thank you. Our next question will come from the line of Joe Schwartz from SVB Securities. Your line is open. Hi, this is Beth on for Joe. Thank you for taking our question. We were just wondering if you figured out maybe mechanistically what's driving these hypomagnesemia adverse events. Do you think it's something related to the peptide construct that you're using? Louise, why don't you give them our lead hypothesis? Yeah. It's a great question. Magnesium is primarily reabsorbed through the TRPM6 channel in the distal tubule, which happens to be the primary site of PPMO localization. This is transient in terms of their concentration. The exact mechanism of how it may interfere, we're working on, but it is specific to the peptide and the fact that we've looked for this in vesleteplirsen and have not seen the same phenomena. It is related to the peptide. Obviously, it's transient, very monitorable and manageable. Thank you. Our next question will come from the line of Anupam Rama from JP Morgan. Your line is open. Hey, guys. Thanks so much for taking the question. Just a clarification question in terms of geography. The FDA hasn't specified any portion of patients that have to come from the U.S. versus OUS for regulatory purposes and approvability purposes, right? I'm just assuming that you can pick up your enrollment OUS to kind of meet the guidance for year-end enrollment. Yes. Thank you. Yeah, that is correct. Obviously, Louise, correct me if I'm in any way wrong, but that's certainly correct. Of course, we, you know, we wanna serve patients in the U.S. as well, even during the trial. Our goal here, while we should be on track to meet our timeline goals for the year, we still wanna move as expeditiously as possible to satisfy the requests for information from the FDA and to get off clinical hold in the U.S. so that we can dose patients in the U.S. and get kids that were being dosed and benefiting from this therapy in the U.S. back on trial therapy. Your point's well taken, that there's no specific percentage of patients that must come from the U.S. Our next question will come from the line of Ritu Baral from Cowen. Your line is open. Good afternoon, guys. Thanks for taking the question. Apologies if it's a bad international signal. Louise, I just wanted to confirm that this patient with the severe event, this occurred while on supplementation, correct? Can you break out between the five or the handful plus this event, which events occurred while on supplementation versus not? Yeah, that's a good question. Just to confirm, he, this patient was already on supplementation as all of the other patients were. They're all on prophylactic magnesium. After this event occurred, his SAE case, he received IV supplementation, and that returned the levels to normal. In the other cases, they increased the oral magnesium, and that brought the levels back to normal. I know it's been said multiple times, but just so we're absolutely clear. All the kids have returned back to baseline. The mild cases were all asymptomatic. The serious adverse event was some sequela and maybe tingling and the like, but it was asymptomatic at time of identifying it and, you know, with additional magnesium supplementation, they all went back to baseline. Our next question will come from the line of Tim Lugo from William Blair. Your line is open. Hey, guys. This is Lachlan on for Tim. Thanks for taking the question. I was just wondering if you had any discussion with the FDA when you met with them about the issue of hypomagnesemia, and if they had any, you know, suggestions or recommendations when you met with them a few months ago before starting Part B. Oh, we had worked closely with the FDA and got their concurrence on the current protocol and the like. The current clinical hold gives the FDA an opportunity to receive additional information and clarifications from us as we hopefully continue dosing in the United States. Louise, is there anything additional to that that you would add? No, that's correct. Thank you. Our next question will come from the line of Gil Blum from Needham. Your line is open. Hi, good afternoon. Just a quick clarifying question. How do you assess if a patient seems sensitive to move to a lower dose? I mean, after first dose, you see a low magnesium levels. I just wanna understand that. Yeah. Yeah. Correct. I'm gonna ask our Chief Medical Officer, James Richardson, to comment on that. Okay, thanks. Yeah, just remind you that for all the patients, they go through a two-month dose escalation period before they're eligible to be randomized to either the high or the low dose. During this period of time, we are monitoring them carefully, and we have an opportunity to observe which patients may be more sensitive to this risk. Thank you. As a quick reminder, that's star one for any questions, star one. Our next question will come from the line of Kristen Kluska from Cantor Fitzgerald. Your line is open. Hi, everyone. Thanks for taking the question. I know in the past when you highlighted these cases that you noted that, there were no occurrences or issues with highlighted markers of kidney function and that these levels have remained normal. Is that still the case with this latest update? I think the answer to that is unequivocally yes, but Louise, you can confirm that I'm right about that. Yeah, that's still the case. Thank you. Our next line, Zhiqiang Shu from Berenberg. Your line is open. Great, thank you. Do you anticipate the following FDA's discussion to implement any sort of screening criteria for the remainder of the trial, such as baseline kidney function? If so, what percentage of patients could even potentially screen out in the real-world setting? Louise. We already pre-screen patients for kidney function, although we're not seeing any abnormalities in kidney function related to hypomagnesemia. As Dr. Richardson suggested, we'll monitor patients during this, the first two months of the study as they're dose escalating, and if they show some sensitivity to hypomagnesemia, we will not randomize them to the high dose and closely monitor as we have been doing. Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is open. Hi, thanks for taking our question. This is Tommie on for Salveen, and apologies if this question was asked already. I was having some connectivity issues. Relating to real world use, can you speak to how monitoring patients there would work, like the frequency that you would be checking for hypomagnesemia? Whether about the enrollment, increasing enrollment ex-U.S. to meet that complete timeline, would you expect that there could be any payer like reimbursement headwinds in the U.S. as a result of potentially having more ex-U.S. patients? Thank you. Well, I'll answer the latter question, then we'll move to the front. The on the ex-U.S. issue, I don't think this is gonna have any impact on the number of patients ex-U.S. versus U.S. isn't something that would normally impact our discussions with payers. I think the data and the evidence is gonna begin to drive our discussions a bit, you know, and we'll have a very good data set. On the first part of the question, perhaps Louise would like to answer that. I mean, regarding the real-world monitoring, this will be informed by the current information we have to date, the rest of the clinical trial. There will be some type of magnesium implementation, and I think that will be necessary, but the data will guide us following those trials. Our next question will come from the line of Gavin Clark-Gartner from Evercore ISI. You may begin. Hey, thanks for taking the question. You mentioned that the hypomagnesemia correlates with the dose. I'm just wondering if it's correlating with any other baseline characteristics, like maybe age, weight, BMI, ambulatory status? Really just wondering if there's any way we could potentially prospectively identify patients who may be more likely to experience it? Thanks. James, do you wanna take that one? Yeah, no, I mean, it's something we're definitely looking at closely. At this point, we haven't identified any baseline predictors, but the thing that we're really focused on is sensitivity in the dose escalation phase, where changes in magnesium are likely to be smaller, something that we can identify and then you know, have patients that are more sensitive to this issue would not undergo the dose escalation. Thank you. I'm not showing any further questions in the queue. I'd like to turn the call back over to Doug for any closing remarks. All right. Thank you, Victor. Thank you all for joining us today, and thank you for your questions. We look forward to providing further updates on MOMENTUM as we make progress with what is a very important program. Now, speaking of upcoming updates, if you will indulge me, I'd like to discuss an update we'll have on an unrelated program. We will have a further update on SRP-9001 in the near future. As you know, we have additional and very important functional and safety data for SRP-9001 that we have been holding off sharing until we could first provide it to the FDA and give the FDA an opportunity to digest it and ask questions and the like. We have done that has occurred, and so we are now able to present that data. I'm very excited. We all are very excited to present additional data on SRP-9001 at the ICNMD conference in Brussels, and that'll occur on July 7th. That data will include, among other things, the one-year data for the 20-patient cohort, one of Study 103, and that's our study of SRP-9001 in the four-to-seven -year-old group using commercial therapy and at the target dose. We will present our integrated analysis of all the patients in the four to seven range across Studies 101, 102, and 103 at target dose. Then we'll have the four-year data on the patients from Study 101. These children now are on average over nine years old, and that means they are in what would be predicted to be the steep decline phase, probably among the steepest decline phase of Duchenne muscular dystrophy. That data is going to be very insightful on the performance of SRP-9001. We will host an investor call around this presentation. I mention this now, so if you're looking for that notification when it comes. At the same time, we do remain in dialogue with the FDA on the feasibility of an accelerated approval BLA for SRP-9001. Those discussions are ongoing, and we will provide an update on them as soon as they have concluded. With that, please, everyone have a good evening. This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.