Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics First Quarter 2021 Earnings Call. [Operator Instructions]. I'd now like to introduce your host for today's program, Mary Jenkins, Senior Management, Investor Relations. Please go ahead.

Thank you, Jonathan, and thank you all for joining today's call. Earlier today, we released our financial results for the first quarter 2021. The press release is available on our website at sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, Dr. Gilmore O'Neill and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements and any such risks can materially and adversely affect the business, the results of operations and trading prices for Sarepta's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. And now I'll turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Thank you, Mary. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics First Quarter 2021 investor Conference call. I am pleased to share with you this afternoon, the exceptional performance we have achieved this quarter with respect to our 3 approved therapies and the significant progress we have made advancing our multi-platform portfolio. Commencing with our quarterly performance, I'm very proud of the Sarepta team's commercial effective fully integrated commercial stage biotech with a focus on execution, we have a well-honed ability to address the often very sophisticated challenges of delivering to and serving patients with a weekly infused therapy for rare disease. From our first launch in late 2016, we have enjoyed compounded growth over the last 4 years of over 19%. And as we have never taken a price increase and price all our therapies at parity, this performance comes from our ability to serve the patient community. I'm very pleased to report in the first quarter, our execution continued, and we achieved product revenue of approximately $125 million, and that represents a nearly 25% growth over the same quarter last year. Our performance comes from our 3 currently approved therapies. As of February of this year, joining EXONDYS 51 and VYONDYS 53, the FDA approved AMONDYS 45 to treat those 8% or more of Duchenne children with an Exon 45 amenable mutation. Having prepared well, we were able to launch on Day 1, including labeling and shipping drug to the warehouse to enable our first patient to be dosed within a week of our approval base. With our third approval, we can now offer therapy to nearly 30% of children with Duchenne in the United States. And from there, we can theoretically build constructs to offer therapy to as many 80% or more of the Duchenne…

Thanks, Doug. Good afternoon, everyone. This afternoon's press release provided details for the first quarter of 2021 on a non-GAAP basis as well as a GAAP basis. The press release is available on Sarepta's website. Please refer to our press release for a full reconciliation of GAAP to non-GAAP financial results. Our total net product revenue for the first quarter of 2021 from our PMO Exon skipping franchise was $124.9 million compared to $100.4 million for the same period of 2020. For the first quarter of 2021, individual net product sales were $107.2 million for EXONDYS 51, $17.5 million for VYONDYS 53 and $0.2 million for the recently launched AMONDYS 45. The increase in sales primarily reflects higher demand for our products. We are reiterating our 2021 sales guidance of $537 million to $547 million for our RNA franchise. We have gained good experience over the past 5 years launching these therapies, and we have now executed for over a year in the COVID-19 environment. These factors serve as a foundation for our guidance. In the quarter ended March 31, 2021, we recognized $22 million of collaboration revenue compared to $13.2 million recognized in the same period of 2020, which relates to our collaboration arrangement with Roche. The reimbursable co-development cost under the Roche agreement totaled $13.4 million for the first quarter. On a GAAP basis, we reported a net loss of $167.3 million and $17.5 million or $2.23 per basic and diluted share for the first quarter of 2021 and 2020, respectively. We have reported a non-GAAP net loss of $122.5 million or $1.54 per basic and diluted share in the first quarter of 2021 compared to a non-GAAP net loss of $79.8 million or $1.04 per basic and diluted share in the first quarter of 2020. In the…

Thank you, Ian, and good afternoon, everyone. With the approval in late February launch of AMONDYS 45, our third PMO-based exon skipping medicine, the team exceeded expectations in the first quarter 2021. As mentioned, total revenue reached approximately $125 million, representing our 18th consecutive quarter of growth since launching in Q4 of 2016. This kind of consistent growth in the face of a pandemic is only possible due to flawless execution by our field teams and home office teams and the determination and commitment of our patients in the larger DMD community. The February 25 approval of AMONDYS 45 casimersen has served as a catalyst to accelerate our momentum even further. While launching during a pandemic can present many challenges, Sarepta has benefited from almost 5 years of building relationships and trust within the Duchenne community. The power of this experience in these relationships are best illustrated by the fact that within a week of the AMONDYS 45 approval, we had obtained access, shipped product to the site of care and dosed the first commercial patient in Florida. It's this of urgency and commitment that goes into driving access for each and every patient. The first quarter of 2021 marks our third approval where we were launch-ready within 24 hours with all facets of our commercial, manufacturing and medical organizations ready for the AMONDYS 45 launch on day 1. We will continue exploring options for patients to safely initiate therapy with AMONDYS 45 in a way that expedites access for amenable patients. We anticipate that the demographics for AMONDYS 45 will be similar to the other 2 populations, EXONDYS 51 and VYONDYS 53 with regards to the average age of patients on therapy and the payer mix. We are pleased with the demand for start forms, and the launch is…

Thank you, Dallan, and good afternoon, everyone. Our commitment to and success in serving the Duchenne Muscular Dystrophy Community has been greatly strengthened by the achievement of a number of critical milestones over the past several months. Just two days ago, on Monday, May 3, we were thrilled to announce positive clinical data in the 30 mg per kg arm of the MOMENTUM study evaluating our lead PPMO-based candidate, SRP-5051. The data we shared included safety, measurements and change from baseline at week 12 and for exon skipping as measured by digital drop polymerase chain reaction or DDPCR and dystrophin expression in muscle by western blood. There were 4 patients biopsied in the 30 mg per kg cohort of momentum, both ambulant and nonambulant. Three of the patients were in their late teens and 1 patient was 7 years old at the time of treatment. Of note and due to COVID imposed delays, Patient 1 received 5 doses of SRP-5051 before he was biopsied, while the other 3 patients received their biopsy after 3 doses. The 30 mg per kg cohort showed a significant dose-dependent increase in exon skipping. SRP-5051, when dosed once per month at 30 mg per kg, achieved approximately 11% mean exon skipping at Week 12. Compared to the PPMO 20 mg per kg dose, we observed a greater than fourfold dose-dependent increase in exon skipping after only a 50% increase in dose, indicating that we have hit the steep part of the dose response curve predicted by our preclinical model. When compared to the current standard of care eteplirsen, we observed an 18-fold increase in exon skipping. Now in terms of expression, the 30 mg per kg dose of SRP-5051 resulted in more than 6.5% dystrophin protein expression as measured by Western Block, representing a greater…

Thank you very much, Dr. Gilmore. Jonathan, let's open up the line for questions now.

[Operator Instructions]. Our first question comes from the line of Gena Wang from Barclays.

This is on for Gena. So one question on the potency assay for Study 301, I think you mentioned in the past that FDA had agreed with your approach of posting but we recently got many questions on this after Pfizer's step back. Could you confirm that all the potency assay matrix has been cleared and you don't need to do any additional work before dosing patient needs 301?

Yes. Thank you for that question. For those who, I'm sure everyone saw it that Pfizer noted today that they - they're still in discussions with the regarding their potency assay for the release of their therapy for their trial so they can start dosing in the United States. So let me be clear about where we are with this. The #1 issue is that we have to have a meeting with the division as a predicate commencing 301: one, we will recall that in September of last year, in connection with the commencement of what we call Study 103, we had discussions with the agency. We were hung up on potency assays at that time as well. I'm very proud of the team actually within a short 2 weeks or so after that initial meeting, we were able to get a live meeting with the division, have a very productive discussion, come - understand better what they were looking for and devise an approach to a potency assay that they would agree with that would allow us to Study 103. We've done additional work on potency assays even since then. So we continue to evolve. Now we have most significant thing we have to do is actually take all of our work, CMC and our protocol for our next trial and then have a discussion with the agency, and we're going to target that for the middle of this year. We feel very good about where we are. We feel very good about our potency assay. We feel very good about the data that supports our potency assay. And all of the rest of our CMC. This is one of the many things that make up the characterization of the product. But so we're clear, we need to actually comply all of that and have an active discussion and a dialogue with the division. And we're going to try to do that as soon as we have the 103 data, and we're going to now be right around the middle of this year. And then our goal is to start our next trial assume thereafter as we are permitted to do. Now with that said, Dr. Rodino-Klapac, if I missed anything, is there any nuance for to mention?

No. I think you got it perfectly. I won't add anything.

Yes. Just a follow-up on 301, what are the remaining gating factors for the initiation?

The big - the two big ones are - we got to get the 103 data. So just to remind everybody, Study 103 is a very important trial for us. That is the trial where we're going to look at the performance of the therapy, both expression and safety in patients with Duchenne muscular using our commercially representative material, the actual process that we'll be doing all of our future trials on the next 301 as well as the commercial material, both in the United States and outside of the United States. So number one is we have to get that data. And of course, you've heard in my opening remarks, we'll have that data this quarter. And once we have that data and it's been we'll share it with the investment community and with the rest of the world. And that will happen this quarter. So that's the one big issue that's the And then the next - and then the second 1 just saying no, but it is basically done, is that we needed to gain as much insight as we could from Part 1 of Study 102. That's the study that we reported out in January to really hone the protocol for our next study, Study 301, and we have done that. And we've made enormous progress and really believe that the insight that we gained for part in Study 102 has been invaluable. It should increase the probability of success in that study. That's been done. And then with all of that and all of our CMC material as well, there's a lot of CMC data. We need to meet with the agency. We'll do that around the middle of this year. And as soon as we've done that, we get the concurrence from the division. We'll commence our next study. And as everyone knows, we'll move as fast as we can thereafter.

[Operator Instructions]. Our next question comes from the line of Tazeen Ahmad from Bank of America.

So Doug, my one question to you is about time line for Study 301. If you are able to start the study sometime this summer, is it your expectation that you would be able to enroll by year-end, just given the calculations that Pfizer provided on its call, it does seem that you could significantly narrow the gap between completion of your study in there? I just wanted to clarify your thoughts on that.

Yes. Thank you for that, Tazeen. So of course, no one will be surprised to hear us say, we want to move as fast as possible. And so we want to get this meeting with the agency as soon as we can. We have to have the Study 103 data in hand to have that meeting. I think that meeting will occur around the middle of this year. And then we want to start as soon thereafter as we're permitted to do. The timing - the full enrollment will depend in part on the end of the study, of course, and we're still refining that. I'm not going to provide kind of detail on that because that will go into some of the work that we've done on the protocol, but we want to move as fast as possible. I would note that Pfizer - I don't remember the number of sites that Pfizer has ex-U.S., but we'll have significantly more sites onboard. So we should be able to rapidly enroll that therapy. Our goal would be to be able to do it by the end of this year or soon into next year as we can from a pure operational perspective. But I think a number of things that we need to consider. One, consider that we will have a significant number of sites up and running over the course of this year if we can commence that study as soon as possible. And the next big thing to also understand is that there's going to be an enormous amount of demand for this trial. So I don't think there's going to be a patient demand issue that's going to slow us down. So it's really incumbent upon us, first, to get the concurrence from the agency to commence…

Our next question comes from the line of Josh Schwartz from SVB Leerink.

This is Kelly on for Joe. On your call back in December for the 20 mg per kg SRP-5051 group, you had mentioned there was a slight delay in muscle biopsies due to COVID-19. Could you give a little bit of color on the average time from last dose to biopsy in the 30 mg per kg group? And could this difference in biopsy timing can found the dose response comparison we might be looking at?

I don't think we had any significant issue on the biopsy, but times for the 30 mg, but I will turn this over to Dr. O'Neill could comment on that.

Thank you, Doug. In fact, there were some delays actually in those muscle biopsies. However, because of their duration, we do not believe that they can found the comparison anyway. In fact, if they were to do that, they would have confounded against the 30 mg per kg. I think that we are very confident in our conclusion that we're seeing a definite dose-dependent effect and that we are actually seeing a robust response and very importantly that we are on the steep part of the dose response curve as predicted by our preclinical market. So in summary, we are very confident that our results and from the conclusion for our results, we about the robustness of the expression effect then.

And one final thing, I wouldn't note. For those who wonder, I mean, I really - remember the following. The thesis is pretty straightforward. Tissue exposure leads to exon, skipping leads to dystrophin, production leads to functional benefit. Look at the exon skipping. For those who wonder, look at the significant multiple increase in exon skipping that occurs at the 30 mg per kg. That should be very predictive of a significant benefit over time. And then look at it versus EXONDYS. If you want one wonders why we feel very good about the results that we have and about the potential at least that we have to confirm in future studies in our Part B, the potential for a profoundly improved therapy versus EXONDYS simply look at the fact that we're seeing 18 full, literally 1,800% more exon skipping over EXONDYS. And we're seeing that at 12% of the dose exposure in half - just about half the time. So we do feel - we feel very good. And then again, Dr. O'Neil mentioned in his opening remarks and apologies for belabor it, but all of the kids. It's a small cohort, it's only I get that. But all of the kids in the cohort that we looked at in Part A were significant responders. There's no one responder that drove anything here. And we did see one significant responder, that was the 12% kid. But all the other kids responded as well and the only difference that we can find between the 12% kid and the other kids is that 12% kid had tumor are doses than the other. So when we look to the future and we predict the potential of this therapy, I would keep that in mind because that is a pretty important signal for what we think we're going to see if we look at this therapy over, let's say, 6 months or even over 12 months, what we might see in the way of dystrophin production and then, of course, ultimately benefit from this therapy.

Our next question comes from the line of Brian Abrahams from RBC Capital Markets.

This is Steve on for Brian. Just as a clarification where any functional data collected at baseline from the patients enrolled in Study 103? And do you plan to assess or report functional changes from these patients?

The kids, I'm going to say this and then you're going to Dr. O'Neill or Dr. Rodino-Klapac We do take functional measures with the kids in 103, but there won't be any report on that for a host of reasons. It's an open-label study. There won't be a report on it immediately. I'd say when we announced you the results in this quarter, we'll be providing results on expression and safety, I wouldn't envision so results. Number one, it's an open-label study. But more important, number two, it's a very early time point. We're looking at kids after just a couple of Mindstone therapy. But perhaps I misstating things. So I will ask Dr. O'Neil to confirm or deny my statement in that regard.

No, I think you summarized nicely.

Our next question comes from the line of Alethia Young from Cantor Fitzgerald.

This is Emily on for Alethia. I was wondering how are you thinking about running studies for some of the other limb girdles beyond 2E? Is there a way to potentially do a basket trial or are they two?

So yes, there would - the short answer, probably not the most satisfying answer. The short answer is we're looking at a lot of different approaches right now to the - and there's a lot of ideas we have and potentially some basket studies around some, for instance, the starts are other very similar therapies or the kinds of things we're pondering. But the predicate for all of it has to be a discussion with the pathway for limb-girdle Type 2E. Because that will really set the framework within which we could have discussions about the efficient pathway for all of these therapies. So we have a number of different ideas. I don't want to get too far out of my skis around them until we've actually met with the division. We will do that this year. As I said in my opening remarks, we really want to prioritize that right behind 9001, simply because we don't want to overburden the division and our own team as we're dealing with the various things we're dealing with. So we'll first focus on 9001. We'll have a meeting on 9003, hopefully, very shortly thereafter. And our goal is to find a very efficient pathway and hopefully, you get started on what we like to believe will be a pivotal trial this year, but we'll have to do that with the concurrence input from the division. And there's a lot of reasons why we think we should be able to move quickly. Just to remind everybody with respect to SRP-9003, and this is similar to most of the other limb girdles, if not all of them, we're dealing with the native protein. These are all monogenic diseases characterized by the absence of a protein, usually a structural protein and the absence of that…

Our next question comes from the line of Gil Blum from Needham & Company.

Congratulations on your progress on the pipeline. So we've discussed the potential for accelerated approval in the U.S. for SRP-5051. Maybe going on the global aspect of this, would there be challenges in enrolling a randomized study for SRP-5051, assuming a placebo control, for example?

I apologize. I missed the piece of it. It cut out. Can you repeat the last part of the question, apologies?

Yes, absolutely. So when thinking of a global study for SRP-5051, could there be potential challenges in enrollment if there's a placebo arm?

Well, I will say. I don't think there is going to be significant challenges in enrollment simply because Duchenne Muscular Dystrophy is a devastating 100% fatal disease. I will also say, and let's not kid ourselves. In this rare disease, it is a very painful thing for patients to the times accept the concept of placebo-controlled track. They're willing to do it. We've seen this over and over again. We've done it with which is a very significantly longer placebo-controlled trial. We've done it with Study 102. We'll do with the upcoming 301. So I'd say we've got to be very mindful about these issues and think of the patient first on things like placebo-controlled trials. I do think that the ultimate answer is that we need a placebo-controlled trial. I do think we can enroll it. And I think patients will do that, particularly if it's a thoughtful program. I think the good thing about 5051 is that we make dystrophin very rapidly. So perhaps that means we can have a more moderated approach to this - the length of the study. Now as long as you're talking about ex-U.S., I think it's important to really focus on the value to the patient community from SRP-9000 - sorry, 5051 with respect to If we look back historically, our PMO, EXONDYS, VYONDYS, AMONDYS, those have all been approved through the accelerated approval process in the United States. On the basis of a biomarker that reasonably predict clinical benefit, and then we've got studies thereafter on that. That mechanism doesn't exist outside of the United States in really any significant way. And so that limits our ability to take that approach ex-U.S. and bring the PMO forward. So we do get ex-U.S. sales, and we have a managed access program ex-U.S.…

Our next question comes from the line of Colin Bristow from UBS.

Congrats on the quarter. So on 9001, you mentioned that the linear QPCR method is achieving expression levels which were greater than you saw in Part 1 or Study Looking at my notes, I think you said that you saw no correlation between dystrophin expression and function in Part 1. So can you confirm whether you saw a threshold relationship with expression levels and could you maybe put some levels around that? And then just another quick one. Could - is there any interest on your part in pursuing a filing strategy with the FDA based on the 4-to 5-year-olds, obviously, assuming endeavor looks okay.

Yes. So on the first one, I want to make sure we did - I'm not suggesting there's not a correlation between expression and function. There unquestionably is, and that's why we're really maximizing expression is extraordinarily important to us. I think what we were saying before, just to put a fine point on it is, when we look at the Part 1 and Study 102. When we look at the 6- to 7-year-old, which is really where you look, and you ask why did we missed the primary endpoint, it was the 6- to 7-year-old, and it was the baseline characteristics. And it wasn't the fact that we had variability in titering. In fact, we had variability in titering for the 4- to 5-year-olds, and we knock it out of the park. So just so we're very clear about that. We do think that more is better with respect to dystrophin, but the 28.1% we had in Part 1 of 102, we believe, had we had the baseline characteristics right, it would have correlated to significant functional benefits and we would have hit our primary endpoint. So that's really what we're saying there. We don't have further data on the upcoming call. We should have that on 103. We'll be getting that data in the very near-term from an expression perspective as well. And then on the pathway forward with the division, let me say that we are not without we want to be creative to find avenues to bring this therapy as rapidly as possible to patients suffering from Duchenne muscular dystrophy. And so we'll have wide-ranging discussions with the agency over time. I think for planning purposes, I think, it would be wise that people for planning purposes to presume that it is Study 301 that will be our pathway to approval in the United States as our base case assumption. And that's really the, I think, the most probable approach that we're going to take isn't to suggest that we don't have other ideas, and we're not thinking about things and we don't have discussions. With the division, but I think if we're going to plan, I think people should plan for 301 being the mechanism and that means we need to get to the division. We need to show them our CMC in protocol, get their concurrence. We need to start 301 as soon as we can this year. We need to get that enrolled as fast as possible. We get a readout of that as soon thereafter as possible. It will be a 52-week study, and we could be in a good place to file a BLA if we were successful in the United States, and we're not very far into the future, if we can just get going this year. So that's - that, I think, has to be our base case assumption, all of us.

Our next question comes from the line of Danielle Brill from Raymond James.

Yes. This is Daniil on for Daniel. Just very quickly, you mentioned previously that you plan to enroll additional 4- to 5-year-olds in Study 103. Just wanted to ask if been completed in those patients? And do you need to wait for those data before meeting with the agency to discuss plans for Phase III?

So we're going to answer the last question first. We're not going to wait. So the meeting with the agency is going to be founded on the original, the first 11 patients. So our initial cohort of patients. We did update the protocol, as you may recall, so that we could add some additional patients to the protocol. We did that for purposes of sort of creatively thinking of what kind of data sets we need if we were going to have far more managing discussions with the agency about faster pathways in the United States. Toward that end, we've lost a significant number of them. I don't know if we've dosed - I suspect we haven't dosed all patients yet, but we've dosed a significant number of patients. Well, actually, I think, let me open the line to Dr. Louise Rodino-Klapac. I can't tell us. She's agreeing with me or disagree with me?

Yes. Yes. All of it.

So apologies. We're better than I thought. I apologize for that of those patients. But any event, we don't - we are not going to wait. We don't wait for the outcome of those patients for the FDA. We are going to - are meeting with the FDA is predicated on our first governor patients. And that will accrue, as I've said before, around the middle of this year once we get the 103 in hand. Apologies for misstating.

Our next question comes from the line of Brian Skorney from Baird.

This is Luke on for Brian. On 9001 on 103, again, I guess what can we expect to see in terms of individual patient level of expression?

Well, I don't know if we've made all the decisions on the exact presentation. Obviously, we haven't seen the data yet. I think broadly speaking, what you should look for is the expression data which will be both western as well as and the safety data. That's the information that's going to tell us about it. I think one of the things that I - that's the primary information. That will tell us about the performance of the therapy, that will tell us about what therapy we have for purposes of our clinical trials and that will give us a view of what this commercial process material is going to look like when we get approved and then the nuance details of that we haven't worked out obviously yet.

Our next question comes from the line of Salveen Richter from Goldman Sachs.

This is Sonya on for Salveen. Beyond DMD, what other indications can the PPMO platform be applied to? And would you be able to do that in parallel?

Yes. That's great. I'm laughing because we were having this discussion just today, and I was saying, I don't want to get out of my skis and promise the particular disease dates. There are a number of diseases that may vary - there are very serious diseases that may benefit from the steric blocking technology. And we've talked about them in the past, and you'll see them, and we actually have some IP on some of them. But the discussion changes even more significantly when you have not only a really precise therapy like our PMO, but you have a very - a much more potent version of that with our peptide conjugated PMO. So I guess what I would say is I don't want to discuss additional diseases or I feel like I'll be committing myself to things that we haven't yet decided as an organization, but there is a cascade of opportunity here. So let's think about the near-term and the mediate and then right after the immediate. Mediate is get through the agency, get their concurrence on the approach and with their concurrent start Part B for 5051 itself. The next big opportunity for us is the other exons. Remember, we're not an exon 51 company. We're a BMD company. So the wonderful thing about our technology and the wonderful thing about exon skipping is there are a very few mutations that wouldn't benefit from exon skipping and where this wouldn't work. So we could at least theoretically, we can get to over 80%. I think the estimates are up to almost 85% of kids with Duchenne where we could build constructs to serve them. That's the next big opportunity. The next big opportunity, and this is a massive opportunity, in my view, is expanding the regions…

Our next question comes from the line of Tim Lugo from William Blair.

So as you start to think about ex-U.S. and the PPMO platform, you signed a deal for ex-U.S. for microdystrophin gene therapy. Can you maybe discuss why you would take TPM to Europe on your own, while you still have a partner for the gene therapy product and kind of your thinking around go alone versus partnership with PPMO?

Well, we'll have to have some discussions with our partner, Roche, regarding that. But Roche has an option to the RNA technology ex-U.S., so we'll have discussions with them about that. But either way, I mean, let me be very clear about this. Our first and foremost goal is to develop therapies to benefit children around the world, including with Duchenne muscular dystrophy. And either directly ourselves or through our partner, Roche, or through someone else, we're going to serve that community. So your point is a good one. I mean, the approach that we take to get in the therapy to other places around the world may vary depending on discussions that we have with others, including our partner, Roche, that we're there with SRP-9001. But we'll get this the therapy there at is successful, we're going to do everything we can to make sure that kids around the world get access to this therapy.

Our next question comes from the line from Cowen.

This is on for Ritu. Congrats on the recent progress. So based on your insights gained from Study 102 Part A and apology that this is an ongoing process, but what might Study 301 size inclusion/exclusion criteria look like? And would it have an interim analysis built in like perhaps also looking at content via MRI at an earlier time point. So any color there would be really useful.

Yes. So let me be very clear. Those are great questions. And I apologies to frustrate you and tell you that I'm not going to answer, then I apologize. We have done - and they're all the right questions. What's the right in, what's and how we're looking at endpoints, what's the exclusion and inclusion? Are we were finding things? Are we looking at other aspects in the trial? So we built the protocols around a lot of the issues that you raised. I will - there's a couple of reasons why I want to wait to discuss the protocols with the outside world. First, of course, is that the protocol in a very real sense is tentative until we have discussions with the division and how to get their input and get their views. And the second one, of course, is that we have a lot of - from our perspective, a lot of insight and proprietary insight around the thoughtful way to build the next trial in a way that will maximize the probability of success and speed. And so we want to meet with the agency, get their input. And then we will provide all of that information, but it will be post the meeting with the agency at or right around the time that will commence that trial, and we'll share it with the world.

Our next question comes from the line of Difei Yang from Mizuho.

This is Alex on for Difei. So just one on the LGMD gene therapy program and the recent presentation at the NDA meeting in cohort 1, we saw increasing dystrophin expression over time. But BCM and protein intensity was a bit lower, was going down over time. I'm wondering if you could give us some details on that? How should we think about that? And are we reading too much into the VCN data here or was there any changing methodologies for these measurements?

I think Louise is going to say, we're probably be reading too much into the but I'll turn it over to Dr. Rodino-Klapac to respond.

Yes. Just to - so we start beta-sarcoglycan expression by multiple measures by what strategy said and also by fluorescent by a number of positive fibers, intensity and the vector copy and those were all within the range that we saw within the first cohort. So we didn't see anything significant in terms of drop in. We're very pleased with the durability that we saw over that course of time and also the increased destruction associated protein conflict. So we're quite pleased with the results we saw two years in the low-dose cohort and continued in the high dose as well.

Our next question comes from the line of Anupam Rama from JPMorgan.

This is Tessa on for Anupam. Just one question from us. Bridging from the Pfizer news earlier this week, a question that we've been thinking about is if every DMD gene therapy sponsor could run into some of the similar issues with respect to the potency assay that you have overcome. What are your thoughts here? And what advantage could if you guys are the only ones who can dose in the U.S. for a gene therapy trial?

Yes. Thanks. Obviously, we were the only one that had the ability to start the trial in the U.S. advantage to that would be astronomical. I don't want to get out of my skis and say that. I want to - let me start with an enormous amount of humility. We've got to meet with the division ourselves. Now I do think that we have benefited from the fact that we had an opportunity to dialogue around potency assays and expectations with the division last year in the sort of September into October time frame. And I'd like to believe that that's really benefited us and really provided us with the kind of direction. And we've built our potency assays and even evolved our potency assays based on those discussions so that as we prepare for our meeting with the division around the middle of this year, I can at least say that we are confident in our data package. I think we have a very good data package. I think we have, I think, a very thoughtful approach to potency assets. I think the data that we have on things like - I'm just focused just on potency, but things like on the potency assay is very good, very positive data, and we think we have a very strong package. I still want to be very clear. We've got to meet with the agency ourselves, and we got to talk CMC and talk to protocol and get the agencies blessing and then we'll commence our next trial. I think dosing in the United States is a very important issue, of course. And I'm not targeting one even needs me to say that. And so it's a big focus of ours to have a successful meeting with the agency. I think we're going to be in great shape with it. Let us assume that the Study 103 data looks good as well, we'll have that data shortly. And then all of our CMC data, with our 103 data with the data that we've seen in Part 1 and 102 and our protocol, I think we'll have a very productive discussion with the division. And then hopefully, if all goes well, be able to start that dosing in the United States and around the world very shortly thereafter this year.

Thank you. This does conclude the question-and-answer session of today's program. I'd like to hand the program back to Doug Ingram for any further remarks.

Okay. Thank you very much, Jonathan. Thanks, everyone, for joining us. And thanks for your very thoughtful questions this evening. I think it's pretty obvious from our remarks and from our answers to the questions, but we have a lot to do this year. We have a very focused team. We'll have a number of very significant readouts and milestones over the course of 2021 into 2022. I've got, in my view, a fantastic team, the best team we've ever had, a very focused and energetic about getting things done and advancing these therapies. And certainly, as we all know, we have a mission that matters. So we're getting up every day, fighting like mad to advance these therapies and improve the lives of patients with rare disease, including, but not limited to, the children who have Duchenne muscular dystrophy in all of the children and adults who have the various limb girdles on which we're developing therapies. And that is only the tip of the iceberg of the work that our team, including our research team are doing to advance our programs. So thank you all very much, and I look forward to additional updates across the course of 2021 as we read them out.

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.