And Louise, do you want to take the question about the timing of expression data in cohort A?

Sure. So you asked about the endpoint. So we expect to have the data on ALI. The primary goal of that study was to reduce that. We are collecting the biopsy data at this point. I'm not sure about the timing of that data, but the primary goal of that readout especially with taking data to the agency will be for the ALI and we will produce the biopsy data. I'm not sure on the timing of that at this point.

One moment for our next question. Our next question comes from the line of Mike Oles of Morgan Stanley. Your line is now open.

Good afternoon. Thanks for taking the question, and let me add my congratulations to Mike as well. Maybe just with respect to the RNA data updates expected later in the second half, you know, should we expect those more towards year end, and will you share those updates together, or do you plan to separate them out? If I remember correctly, I think FSHD may be a little bit ahead of DM1. Thanks.

We've said that those data will be available later on in this year, and at this point we're not able to be more specific about the timing. We're going to look at each data set as they become available and make them public in an appropriate fashion. So I really can't comment today as to whether it would be at the same time or staggered. It depends on the availability of those data. But again, both are expected in the second half of this year, and we're on track to meet that timeline. Louise, is there anything you'd like to add?

No, that's correct. Thank you.

Okay, and maybe just very quickly, just to add, Mike's exactly right. We do think about these programs as separate programs, though. Obviously, the timing on the SAAD data, they were very close and it made sense to release the data at the same time. But just generally speaking, we do think of these programs separately. So, to Mike's point, when they become available is likely when we would release it. That's how we're thinking about it generally as a program.

One moment for our next question. Our next question comes from the line of Salveen Richter of Goldman Sachs. Your line is now open.

Great. Thanks for the question. This is Matt Ong for Salveen. Maybe building on a prior question, could you provide any more color on the metrics beyond start forms that you are seeing that support deeper elevatous penetration in the ambulatory patients? And how are you thinking of the longer-term trajectory now? And then also, how might you be able to leverage some of your efforts here to support non-ambulatory use if that's eventually included back in the label? Thank you.

Absolutely. Our strategy is set. And as I mentioned, the sales team is out there. They've been trained. They're deployed. And the broader commercial initiatives are fully operational. So we're seeing enrollment form activities stabilize and improve. We've got returning sites that are re-engaging. And we're seeing interest from new sites We're also seeing a directional alignment between healthcare provider engagement and enrollment form submission. So when our sales team goes in and speaks with an HCP, we see enrollment forms result after. As I've mentioned, in some cases, as soon as 30 days after that engagement. Those signals to us that those initiatives that we put in place are starting to take hold, and it's strengthening our patient pipeline. Even though the associated revenue contribution, it's going to take time. Our team is just focused on consistent execution and helping those patients progress through the journey.

One moment for our next question. Our next question comes from the line of Barron Ammon of Piper Sandler. Your line is now open.

Yeah. Hi, guys. Thanks for taking my questions. Maybe three-parter for me. On Amandus and Beyondus SMBA, Has the FDA indicated if there are any plans to hold an advisory committee meeting? So that's the first question. Second question on FSHDs, there's a direct transcriptional target of Dux4 that apparently correlates to clinical disease severity. I wonder if you're looking at that in the current trial. And then the last one on cohort 8 data, is there potential to revive the LGMD gene therapy programs after those cohort 8 data? Thanks.

Okay, I'll start off and then I'll pass to Louise. With respect to the Amandus and Biondus reviews, the FDA has not indicated at this time that they have an intent to schedule an advisory committee. Obviously, they can make that decision at any point, but to date, they have not made any indication that they intend to do so. Louise, do you want to take the questions about the endpoints?

Sure. The second question, I was on FFHD and the CHUX4-related genes, and so it's Certainly, we're looking at both a downstream DEX4 gene panel, but then also I think to your point was around the DEX4 biomarkers. And so our team is looking at multiple circulating biomarkers and evaluating them right now. So both validating the assays and then looking at them in our models. And so certainly that is something that we are actively looking at because having a circulating biomarker is a huge advantage in these indications. And then I believe the last question is on the limb girdle pathway following cohort 8 data. And that's exactly right. So for LGMDQE, as we've discussed before, right now we're on clinical hold. And in order to get off clinical hold and potentially submit to the BLA, that's based on the cohort 8 data, as we've discussed with the agency. So as soon as we have that data, will be able to discuss the pathway to submit the BLA with FDA following that data as well.

One moment for our next question. Our next question comes from the line of David Holmes of Deutsche Bank. Your line is now open.

Hi there. Thanks a lot for taking my questions. So I want to ask about the PMO franchise and your perception of the durability there. and in particular, how should we think about modeling the franchise next year, especially with Exondus, where we have a potential market entry of a competing Exxon 51 skipper? Thanks a lot.

I'll start and probably pass it to Patrick for a little bit more detail. We have a tremendous amount of confidence in the durability of the PMO franchise. This is a franchise that has a very long track record, 10 years for the first approval, and has delivered benefit to patients over that period of time. There's extensive real-world evidence supporting benefit as well as supporting a favorable safety profile. And so we feel that we are in a good position to enter a competitive market and to maintain momentum in that franchise. It's a bit early to predict exactly how those dynamics will play out from a modeling perspective but we think any impact that competition would have would likely take some time to become visible. One has to overcome a number of hurdles when one enters a market like this. There are reimbursement pathways that need to be established patient assistance programs that need to be put in place if the sponsor, in fact, intends to do that. For example, with our PMO franchise, we have home infusion support and a number of things that contribute in addition to the overall benefit delivered to the very high rates of adherence that we have observed, 90% or greater. And so we would expect that impact of competition, if it were to come to be later on in 2017, Patrick, do you want to add any additional color?

You covered it very well. Our position is grounded in that decade of experience supporting patients, families, physicians, and those treatment centers. As you mentioned, we've got a body of real-world evidence, established safety experience, adherence rates exceeding 90%, and we've got a team that's very well versed in working through any reimbursement challenges with the providers and the institutions in order to get patients authorized and reauthorized and keep them on therapy. And so all of that points to the mature infrastructure that we have and we're going to lean into as we support our patients.

One moment for our next question. Our next question comes from the line of Mitchell Kapoor of HC Wainwright. Your line is now open.

Hi, this is Jadon from Mitchell. Thanks for taking our question. So going back to Amandus and Beyondus, regarding those SNBA submissions, do you have any thoughts on timing for converting Exondus to full approval? As you guys spoke about, as of next month, it'll have been on market for a full decade, but it's been on accelerated approval that whole time. and additionally, can you speak a bit on the recent Capricor adcom meeting? Do you see this increased scrutiny of post-hoc data reevaluation as a negative read-through for Amandus and Beyondus, given that the data did not achieve traditionally accepted statistical significance in the trial? Thanks.

So with respect to the Capricor adcom, I think the issues that were discussed at that adcom were particular to the package that CapriCar brought forward and the FDA's review of that package. Obviously, we don't comment on other sponsors' review process, but we don't see read-through to our program. When we look at the applications, They are supported not only by the clinical trial data, but by extensive real-world evidence. And we believe together those present a strong package for conversion to traditional approval. With respect to the strategy for Exondys, Louise, would you like to take that?

Sure. So for Exondys, We don't have a confirmatory study as part of that. We have a post-marketing commitment, which is our mission study, which is a dose-ranging study. And that study will be done by the end of this year. And so following that study, we'll have discussions with the agency in conjunction with the Vyondus and Amondus as well. And so that's where we're at in terms of the potential conversion of Exondus to traditional approval.

One moment for our next question. Our next question comes from the line of Andy Chen of Wolf Research. Your line is now open.

Hey, thank you for taking the question. Welcome, Michael. Regarding the MAD data in DM1 with the functional endpoint, I think, Louise, you mentioned that the goal is not, or the primary goal is not to establish functional efficacy with the dataset. Can you please clarify the reason behind it? Is it because you don't have visibility yet and the sample size is too small for you to make a conclusion? Or is the empirical result tracking in such a way that you can't conclude that it's better than competition? Thank you. Louise, do you want to address that?

Yeah. So for FSHD, it's really around the timing of the data. So as I mentioned, FSHD is a very slow, progressive process. and the data is at six months, so we would not expect to see a strong signal at six months, so it's really about the timing of that. James, would you like to add anything around the disease itself and the way we think about functional outcomes in this indication?

I mean, I think you've got it, Louise. FSHD is a slowly progressive disease. We expect the treatment here to improve symptoms we expected to stabilize the disease, similar paradigm to DMD, and we need time for the disease to progress to show the therapeutic effects of stabilization. This is very much in line with other developers' further advances in the field as well.

One moment for our next question. Our next question comes from the line of Brian Scorny of Baird. Your line is now open.

Hi, this is Luke on for Brian. Thanks for the question and also wanted to offer my congrats to Michael. So on the Huntington's program, I guess you have an idea of when we might see the phase one data. And can you remind us if you're measuring protein knockdown and if you think the study could support some initial biomarker proof of concept? Thanks.

Luis, do you want to take that?

So we expect the first proof of biology data early next year. And really, this is early single ascending dose data. And what we're looking for in this study is safety and then early signs of efficacy. So are we getting past the blood-brain barrier? And to do that, we're looking at knockdown of punctuitous, and that'll be in the CS path. So that's what we'll be looking for in terms of validation of the platform, along with safety and the ability to dose escalate.

One moment for our next question. The next question comes from the line of your Zoo of Wells Fargo Securities. Your line is now open.

Oh, hey. Thanks for taking our questions and congrats to Mike on assuming the CEO role. A question on cohort eight. Is the ALI data all that's needed from FDA to make a decision? And if that's the case, could the decision be a reinstate, the indication? And another question on the Biondis and Amondis, the SNDA, the review time seems to be eight months. I was wondering if that, it doesn't seem like either priority or standard review. Could you talk about what timeline is that and what might be the implication? Thanks.

Certainly. So with respect to Cohort 8, our strategy is to complete Cohort 8 and as soon as we have the 12-week data completed, approach the FTA to discuss the regulatory path. So we can't comment on that regulatory path today, but we will be engaging with regulators with data in hand to define that path. And we believe that the cohort A data, when they are available, together with other data sources like Endure, can make a compelling argument for benefit-risk in this population. But obviously, that will be discussed with regulators, and the exact nature of the path will be defined at that time. With respect to the Amandus and Biondus review, it is a standard review.

One moment for our next question.

No, I just want to clarify, it was 10 months from submission, not five.

Our next question comes from the line of Tahzeen Ahmad of Bank of America. Your line is now open.

Hi, thanks for squeezing me in. I just wanted to clarify a comment that you made about the potential for an accelerated path for, let's say, DM1 in the future. As it relates to the competitive landscape, if, let's say, one of the programs that's ahead of you in development, let's say Novartis, is able to get an accelerated path, do you think that would lessen the chances that Sarepta could have, even with compelling data, to get an accelerated path as well? Thanks.

Louise, would you like to take that?

Sure. Certainly, as I mentioned, we'll evaluate the regulatory landscape as we proceed and our study is designed to be ready and available for both accelerated or traditional. Certainly, having a traditional approval makes things, changes the landscape in terms of accessing an accelerated approval and so It'll be facts and circumstances in terms of both the landscape and then where our data as well. And so we'll be looking at both to define that pathway and it'll be come out of discussions with the agency when we do so.

Yeah, so I agree with Louise. The only thing I would add or perhaps emphasize is that these will be data-driven decisions. So it will depend on the nature of an approval in the space if that happens. and the particular strengths of our data relative to that approval. But we will be prepared to go forward for either an accelerated or a traditional pathway, depending on what is most appropriate at the time.

One moment for our next question. Our next question comes from the line of Joe Schwartz of Layering Partners. Your line is now open.

Hi, thanks for taking my question. Welcome, Mike. We appreciate you joining at such an important time and look forward to seeing how you shape the company's future. For the next SRP 1001 and 1003 updates, what quantitative benchmarks does each program need to clear to justify pivotal advancement rather than continued exploration?

Louise, would you like to take that?

Sure. We're looking for Two things out of these studies, or multiple things. We're looking for the ability to dose us glades safely, so get to a dose that's appropriate for the phase three with very strong muscle concentration and significant knockdown. So as I mentioned during my opening remarks, we want to get the highest levels of knockdown that we can in order to affect the biomarkers and also predict functional improvement. And that's all benchmarking back to our preclinical data. And so we're looking for also concentration, knockdown, and the ability to dose escalate safely without any safety signals. And so that's what we're looking for out of these two studies.

Our next question comes from the line of Yunzong of Wedbush. Your line is now open.

Hi. Good afternoon. Thank you very much for taking the questions. So the first question I wanted to confirm, because I thought the original guidance was for data from cohort eight to be available by year end. So was there a delay in terms of patient enrollment, and did you have any challenge to enroll non-embolic patients given the safety concerns? And secondly, can you remind us the efficiency of your Huntington's disease program candidate to cross the blood-brain barrier? And in terms of knockdown efficiency, What magnitude would you like to see, please?

Thank you. Louise, would you like to take those?

Sure. So for the cohort eight enrollment, and so in terms of enrollment, we're seeing the study progress well. We are seeing investigators dose sequentially their patients versus in parallel. And so when we looked at the timing of when we would have the 12-week data, It would be available in Q1 of next year. And so when we have the complete 12-week data from the 25 patients, that'll be in Q1. So that's the reason for the data availability for Cohort 8. In terms of Huntington's program, the knockdown that we're seeing is really based on our preclinical models, and that's both in murine models as well as the non-human primate model, where we saw knockdown levels as high as 80%. and really what got us excited about this is the ability to knock down in the deep brain like regions the striatum as well as the caudate. And so these are really what got us excited and what we'll be looking for. Obviously in humans we can't have that degree of certainty in terms of knockdown within the brain so we'll be looking at CSF knockdown as a surrogate for that.

I'm showing no further questions at this time. I would now like to turn it back to CEO Michael Severino for closing remarks.

Thank you, operator, and thanks to everyone on the call for your time and attention today. As I said in my opening remarks, my first few weeks with this talented team reinforced my view that we have a bright future ahead of us, and my confidence in the potential of Sarepta has only grown. We have four marketed products that make a real difference in patients' lives today. We have a compelling pipeline of siRNA therapeutics that will drive our future growth. And we are executing from a position of financial strength with the ability to advance our pipeline and initiatives independently as evidenced by our strong balance sheet and operating profitability. A number of important catalysts are on the horizon, which we believe can unlock long-term value for patients and shareholders alike. We appreciate your continued support and look forward to updating you on progress in the months ahead. With that, we can end the call. and I hope everyone has a very nice evening.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.