Sarepta Therapeutics, Inc. (SRPT) Earnings Call Transcript & Summary

Okay. Good morning, everybody. Thanks for joining us at the Bank of America Virtual Napa Conference. It's my pleasure this morning to have with us Sarepta as our next presenting company. For the next 50 minutes, I have the pleasure of speaking with Doug Ingram, who is President and Chief Executive Officer; as well as Ian Estepan, who is CFO. Doug and Ian, good morning. Thanks for joining us.

Thank you for having us, Tazeen.

Thank you.

So we do hope to be back to Napa next year, but we're happy that you joined us virtually from Boston today.

So maybe for those that are listening, can you just give us a quick update of some recent events that have happened in terms of data for some of your key programs? And then we can go into a little bit more detail on each of those stuff, okay?

Sure. Let me say, I think that we have been executing. In January of this year, as you know, we had to read-out Part 1 of 102. We had hoped to hit the topline. We missed the topline, but we know exactly why. We've looked very carefully into the data where the baseline characteristics were right in the 4 to 5 cohort. We were very clinically meaningful and statistically and significantly better with the treated group than the nontreated group. I would argue the best results that anyone has sever seen in Duchenne muscular dystrophy the impact of the therapy. And with respect to the older group, the baseline characteristics, which is so wildly different that it was clear to us what had happened. But it helped -- but that by itself was not only confirming to us as the therapy and its benefit, but also helped us think about the way we're going to build our next trial 301 that we are going to get started this year. And then from that moment, we've really executed well and I'm very proud of the team. AMONDYS was approved in February. That launch is going brilliantly right now, really serving the community with exon 45 amenable deletions and of course, as everyone knows, that's our third therapy, we [indiscernible] all really doing very well. We then had a report out on another very consequential moment for us, which is our next-generation RNA technology, the PPMO or peptide conjugated PMO. And the results there were very good. We had what will be about 6.5% dystrophin, that is about 18x exon skipping, an order of magnitude more dystrophin than we get from the current therapy and in half the time and with about 12% of the exposure. So clearly, if we can translate that into an approved therapy, that's going to be really meaningful. And I think all the modeling would say given that we looked at this very early that -- if you looked at it out of the 1-year marker or later we're going to almost certainly going to see more than 10% dystrophin which is -- which should be remarkable. There was safety concern, which was hypomagnesemia, we believe we can manage that. So we're really confident about where we are in there, and we'll be moving to what we hope to be a pivotal trial with that therapy. We'd like to, of course, to do that this year. And then, of course, a lot has been going on in a short period of time. We had the readout of what we call 103. That goes back to 9001, which is our gene therapy for Duchenne muscular dystrophy. And that is an unbelievably important readout. We can talk more about that over the course of this hour. But that is -- the reason that's important is a couple fold. First of all, that is the process, and the release process for the material that we would use not only for our next trial, but for making the therapy commercially available to patients around the world. So seeing the characteristics of that therapy in the commercial process is extraordinarily important on every metric. We were excited by that. The safety profile, we can go into more depth on it, but the safety profile was just as we would have hoped it would look. We don't see the kinds of things that are concerning with other full-body infusions. So we are clearly differentiated from other full-body infusions. We don't see the complement cascade that others continue to see unfortunately. We don't see the kinds of kidney involvement, kidney damage that others are seeing. And then with respect to the adverse events, we do see they are consistent with what we would have hoped, which is we get the kind of most significant one, frankly, is nausea at infusion, which we can address with antiemetics. And then, of course, we occasionally will see increases in the liver enzyme not surprising, but all very manageable and go back to baseline very rapidly with the intervention of the increase of steroids. And then on the -- but then let's go forward then on the efficacy side, on the expression side, just remarkable. We had -- with our commercial process in 103, we got 3.85 genome copies per nucleus. So anyone who wonders whether you could do a full body infusion, get the genes in the right place sufficiently, abundantly there and almost 4 genome copies per nucleus which is, frankly, is tremendous. The expression is very high. We're about 55% on Western blot. If you look at the immunofluorescence, the vast majority of the fibers are being protected by dystrophin exactly what we had hoped, all properly localized to the sarcolemma. And from an intensity perspective to really look at the quantification, we're off the chart well over 100% in the order of 17% of normal on intensity. So we're really excited about that. And then, of course, I realize I'm fast moving into a model [indiscernible] in a second. But we have a lot going on for the rest of the year to track for some very consequential meetings with the FDA. And if all goes well, the consequential commencement of some really important studies over the course of the year, both in LGMD, SRP-9001, 5051, to name the top ones and then we'll have a big readout beginning of next year with SRP-9001, which is Part 2 of 106. So the short answer is, of course, as is always the case with Sarepta we got a lot going on. Things are going very well right now. The team is actually getting out very proud.

Okay. So let's talk about what I think is on everyone's mind, the -- interactions with FDA that you're expecting to have. Where are you in that? So just to give some context, let's talk specifically about gene therapy for DMD. So you released the first portion of the 102 study, obviously, earlier this year. The 103 study results came out a little over a month or so ago. And I believe at that point, it was your plan to engage the agency, get a meeting on the calendar, talk about your plan for Phase III trials design and get their clearance to start. So is that still correct?

It is. So we're going to -- so we've done all the work to prepare ourselves. We have a brilliant, in my opinion, of course, still it may be a brilliant briefing of CMC from our perspective looks fantastic. The protocol for the next trial is fantastic. That's all briefed up. We'll have a meeting with the agency this summer. It will indeed be a live meeting with the agency. And then if all goes well, we'll be able to start our next trial very shortly thereafter then we're going to get going on Study 301, which is an important trial for us.

Okay. So what is the checklist of things that need to occur at this meeting? So have you requested the meeting?

We have. We have. I'm not going to be indicating about the timing of it, but it will be this summer. And we have requested it, it's all briefed up. And it's -- I can really simplify it. It's really here is our CMC. Here are the results of 103, very important, because it helps characterize the therapy for purposes of 301. Here's the great results we've seen there. Here's the protocol for the next trial. I mean it will be a little cagey as well on exactly the protocol is because for confidential reasons, but also I want to share it with the agency to get their input before we start talking about it externally. But I would tell you that that's not a very -- it's not exotic. So I'm not particularly concerned that the agency is going to have a fundamental disagreement. It is, to be clear, I think placebo control double-blinded study, primary endpoint will be NSAA. So it's quite traditional in that sense. So I don't think there's an issue there. And then the fundamental question is we would like to start our next trial, if you agree, then we're ready to start our next trial. I'm confident in our package and I'm confident in our approach. And then if all goes well, we'll immediately thereafter -- very shortly thereafter, I should say, start that next trial deploying as fast as possible.

Okay. So as it relates to CMC, can you walk us through key topics that you think you'll need to address?

Well, there's most of assays, and we're going to have to walk through all of that. I think the 103 data that we've seen is going to be very helpful to show how we'd characterize this therapy and how well it can for us. The issue that you saw in Part 1 of 102, just let's put that on the table and then take it off the table. So Part 1 of 102, you may recall, 3 lots of therapy. That 102 was both the process and the release for Part 1 of 102 was all done through our third-party manufacturer Nationwide Children's Hospital. And the particular type of titering they used, when we went back and looked at it with our more precise titering, which is the linear QPCR titering, there was more variability than we would have liked in the actual titering of the therapy. That's resolved. And you'll see that in 103, it's all resolved. The way the linear process is quite precise, so we'll have no issue there from my perspective. From a potency assay perspective, that seems to be the flavor of the day, concern for people is a potency assay. It's interesting. I don't want to overpromise, but I will say the following. Last September, we had a written response from the agency with respect to our potency assay approach, an approach that we were very confident about. We thought we were very -- we thought it was very appropriate for the program, but that they disagreed with. And at the time, I have to tell you that, that was a very frustrating moment for us, and I would have said a very negative moment for us. But the reality is that the benefit of hindsight, it may have been one of the most valuable things that's occurred because as a result of that, we were able to hustle up and get a live meeting within about 2 weeks of that written response, where we can really delve into what the agency wanted to see from potency assay, both for the upcoming trial, which is 103 and then eventually for other trials, including 301. So based on all of that, we believe that we've done everything that the division would want us to do from an assay perspective and more particularly from a potency asset perspective. And so I don't want to promise in advance of getting the buy off from the agency itself. We feel very good about where we are from an assay perspective and the CMC perspective as well as from a protocol perspective as we track towards this meeting. So we're very confident in this upcoming meeting.

Okay. So I guess a couple of follow-ups. So I think some people are confused by what you're referring to as titration because this is a one-and-done treatment for patients. So can you just give us a little bit of color on exactly the method of delivering this treatment?

Yes. Yes. Let's take -- that's very -- I never thought of this before, right now. Oftentimes in drugs with chronic therapies, you titrate the patient up. That's not what we're talking about. Apologies. That's not what we're talking about. This is really the method that you use for the lot to determine how much of the therapy is in the lot, that essentially are you getting the dose right. So our goal using the linear method, which is our new more updated method is 1.33 genome copies. I mean it's 1.33 to the 14th is the dose that we're trying to get. The titering method for the lots used by Nationwide, which is a supercoiled PCR, we were told that we were hitting all of those. But when we took it, and we looked back using a more precise dosing method, 2 of the 3 lots were actually lower than we would want with this more precise titer. So what that means is, with respect to Part 1 of 102, about 60% of the kids had a lower than the target dose that we wanted from the therapy, at least if you look at it with the more precise linear titering method. It's a very -- now the good news is that even notwithstanding that, where we got the baselines right in the 4- to 5-year-olds, it didn't matter. The kids still hit statistically significant and clinically meaningful benefits over placebo. So even with that titering difference, even with that variability difference, we still saw a strong, strong therapeutic benefit in these kids. But it's important to us to get a more precise titer for a host of reasons. One, if you get to the more precise titer, you're more confident about the kinds of expression at least on meaning that you're going to get and will be able to hold just as we had anticipated. We saw exactly that in 103. We need to have a tight process for releasing the product for commercial purposes. It would not be fit for purpose to have that much variability if we were trying to launch this therapy. The agency will clearly and rightly object to that and so there's a lot of good reasons why we need this more precise approach. But when we get there, we're very tight. And so we've done this now a number of times in the crossover patients in 102, even though that was Nationwide's material or process. We used our linear QPCR titering process to release that. And sure enough, we got about 52 -- more than 52% on Western blot of expression and the reason for that is you got a very tight release. You didn't have the variability that you had in Part 1, which was more like 28% -- 28.1% on Western Blot. Then we did 103, used the same titering method, and we got almost exactly the same as 102. We had about 55% or so on Western Blot. So this is a very important process. So that, I think, is completely resolved, and we feel very good about that titering performance. And then on the potency assay, again I'm not going to give a ton of detail on that, of course, for competitive and other reasons. But we feel really, really good about where we are from potency perspective. And that's going to be in quiet a lot of people's minds, of course, seeing what's happened in some other companies over the last year or 2.

So the Study 103 had 11 patients worth of data. So do you think that that's an appropriate end to account for any kind of variability? You did come to an informal agreement with the agency to do this. But I think people were focused on the fact that it was informal as like in sort of a more formalized sign-off. Correct me if I'm wrong. So have you had additional interactions while that study was underway with them? Or will this be kind of the first time you're having a real interaction with the agency since you had that discussion to tell them about the Study 103.

This will be the -- there have been ongoing discussions at different levels at some level. And I must say OTAT is a particularly busy division, and it is not as easy to have informal dialogue that on a substantive nature with OTAT as compared to some other divisions of FDA. So this and the real sense from a formal perspective will be our next big check-in. With that said, I can think, first of all, I do think the 11 patients is a very significant cohort, particularly given this disease stage. So seeing the results and the consistency of these results, I think, it's really powerful. We have continued to dose other children in different areas. We're dosing additional 4- or 5-year-olds, as you know. We're dosing nonambulatory and overambulatory kids as well. But we haven't had any issues with the agency with respect to that. So I think we're in really good shape as we track to this meeting in the summer.

Okay. Now if you do achieve clarity at the meeting that's going to happen this summer, going to wait for the meeting minutes to come back before you tell the greater public about it? Or how should we be thinking about when we should hear about how that meeting went?

It's a constant. It's funny. Ian is fighting, not smiling because it is constant debate internally. I will probably want to wait until we get the meeting minutes back just to avoid any potential misunderstandings, which would be very unfortunate. So I will probably wait for the meeting minutes before we would formally announce it to public something we think about a lot. So a little bit faster so to guess, but almost certainly we will wait for the minutes.

Okay. So assuming you can start the study this year, how long do you think, rough estimate, it would take you to complete the enrollment? And I know you want to be sensitive about telling us how many patients, but let's say roughly, it's round about what Pfizer is trying to enroll. How long do you think it would take to get there?

I don't -- I'm going to try to beg off making a firm commitment other than to say the following. It's going to robustly enroll. I'm going to make it -- so first of all, we will eventually have 30 or more sites around the world, okay, that's going to take some time. The entire process, the IRB process getting them activated. We've done a lot of the work in advance. So we are going to, over time, have a significant number of sites enrolled. The amount of interest in this therapy among the patients, their families and the investigators is enormous. Like we're getting -- they're not interested, they're pressuring us to get going. I've got some of the big thought leaders around the world constantly saying, we got to get going, get going, got to get this buy-in from the agency and got to get the study going. So I don't want to make a firm commitment of about how long it will take because that will depend on when the agency lets us go and then how fast each of the sites activate, we'll move as fast as possible. I can say that if we can get going this year, we are going to enroll this study very robustly. I think it's going to be a very, very -- it's a long-awaited trial and it's a trial that I think it gives a lot of patients potential hope. So I think it's going to enroll very rapidly.

Okay. So I think the reason I'm asking this question is because there's another program, Pfizer is trying to be straight. So per their last public disclosure, it seems like the study is on a bit of a break from enrolling patients as they got through some questions that they've gotten from the agency and I believe they indicated that they didn't feel that they would have resolution to those questions in the first half of the year. So I guess do you have any idea of what might be happening with that program? And also, can you give us your thought? I think there was another update about another incidence of complement activation observed in one of their patients. So to the extent you can share anything that might be helpful for investors, that would be great.

Yes. Let me start first with us because that's what I can speak confidently about. And anything beyond that is, of course, just me speculating. With respect to the Sarepta, just so we're clear, we are further along than anyone in the exploration of a micro-dystrophin to treat Duchenne muscular dystrophy. We have dosed far more patients than anyone else. We have over 65 patients now dosed with our therapy. We have a very, by now, fairly well-understood and stable safety profile with great expression. We're the only company that has the results of a placebo-controlled trial and the benefits that we're seeing in a placebo control, double-blinded, not a post-hoc analysis trial that's, of course, what we had with the 4- to 5-year-olds. And I think if we can get this next study started right now, we are going to stay very competitive from a timing perspective and I would argue it's highly differentiated from a safety and expression perspective. And I think -- so long as these therapies that were about 6 months of one another, frankly, I think that patients are going to choose the better therapy. So we got to get started on this therapy. You're right. What do -- all I know about Pfizer and their program is what they said. So I want to be very clear. I can only speak to what they said. My understanding is they have not been able to dose in the United States yet. And my understanding from public statements they made is that just their potency assay. I don't know precisely what is the issues with respect to their potency assay. I will only as respect to our own, and we'll, of course, see if I'm right or wrong when we meet with the division. But we feel very confident about the performance of our potency assay. And probably equally important in this environment, we feel very confident that we've done everything that we could steer a great guidance from the agency. We understood much better in September of last year, what the agency wanted to see than we would have understood if we had simply done this in a vacuum. And we think we've addressed all of their issues and we're getting exactly what they want is that's what we believe to be the case. We did hear recently yesterday or day before that Pfizer has notified patient groups that they have seen yet another complement-mediated serious adverse event in their therapy that -- obviously, they've seen this historically, they saw this early on and then they're seeing it yet again. I can't speak to that. I can't speak to what the implications are for their program. But I can tell you we have not seen it. I mean so very clear about this. We dosed 65 kids. There's nothing in the preclinical that would have predicted that we would see it and well we would never see. We did not get any clinical manifestation of the complement cascade or kidney involvement or the other issues that others have seen in a while. We're still hypothesizing the reasons. It certainly would seeing the primary reason it appears to be that it is a very different vector rh74 which is just not amenable to those issues, at least is a much lower risk of those issues that we have seen in the kids.

Okay. So going back maybe a year or 1.5 years, I think you all remember the importance that you were placing on making sure that you had a nice margin of being ahead of Pfizer in the development program. Given where they are right now, given where you could potentially be, is that feeling now important again? Because if we look back to January, I think a lot of investors kind of wrote it off as well. Now perhaps Pfizer is going to have a meaningful lead over Sarepta with the Phase III program or the pivotal program. And so you're delivering a one-and-done treatment, it is really important to be first to market. So how are you thinking about what the potential differences and the time lines for your programs might be now?

Well, in summary, it's hard to say with certainty because I wouldn't remember, although Pfizer had dosed some patients in this Phase III. They've never been able to dose the patient in the United States yet. So then they have not dosed any patients and we've dosed the entire placebo-controlled trial. We've already started dosing with our 103, our commercial process. And if all goes well, we'll be dosing our next trial, starting in the U.S. and around the world, very soon. That's certainly our goal. So I would not argue that they're ahead of us. They certainly got something ahead us, I would argue they are temporarily ahead of us. And then, of course, the other reason why it's very difficult to assess this is it's hard to make, yet make meaning of what happened the last day or 2, which is that Pfizer has announced another -- yet another -- and I did -- I think they had not previously updated the protocol at least this might have helped to mitigate the issue associated with the complement mediated serious adverse events which I guess were really serious when they happen in kidney failure, which is obviously life threatening. They have now announced they're still getting it. They just got it again. And I think they're going to try to amend a protocol to explore whether it'd be prophylactic use of rapamycin would in addition to whatever other protocol amendments they made would mitigate this risk further. So I don't know what exactly that means to be direct. I think they'll presumably provide more insight into that in the next week or so. They're going to be speaking at PPMD, I believe, so I'm sure they'll tell people whether how this is a delay, to what extent this is going to be a delay. How long is it going to take to explore whether the use of prophylactic rapamycin in addition to the other things they've done with the protocol could reduce the risk associated complement. So it's very difficult with all of that to assess precisely where we are temporarily. I do not believe we are behind them. I want to be very clear. Now I like the idea internally that we think we might be behind them because it kind of creates the burning platform that makes us move fast and we will continue to move fast. But I don't believe that such is the case. I also think that first over the line is not all or nothing, I will say that. I think we're within 6 months of one another, either direction, either one of us. The better therapy is going to win the day. I think a patient will wait in 6 months. Patients are not going to wait 2 years, not with this deadly disease. So let's be very clear. I don't believe that's the case. But I think as long as we're within 6 months of each other, the real question that people need to ask themselves is which of the therapies is going to provide the best benefit and the best safety profile at the same time. And you can imagine I'm biased, and I'm very excited about the results we've seen thus far in our program.

So as of right now, you haven't seen complement activation. And given the amount that you've been serving patients from the start of your program, what are the chances that you would see something in the next study in terms of that type of adverse events, do you think?

Leadingly remote at best. I mean, again, I will be very clear. It's -- we didn't see anything like this preclinical. So we wouldn't have predicted it anyways. I can recall, frankly how surprised our Head of Gene Therapy was when she heard that others were seeing it. And remember, the first one was Solid. Solid was the first using AAV9 like Pfizer, started getting these very serious adverse events. We were surprised because we did not anticipate this based on our rh74 preclinical work. And now with those patients, and we've dosed them, as you know, in over 65 kids, we've dosed really large kids, too, by the way. So we're clear because we're dosing not just -- we're using rh74 not just with Duchenne muscular dystrophy, but we're also using it for the neuro program Type 2A, and we've dosed kids that are over 50 kilograms. And again, we just do not see this issue. So science is always, in some regards, tentative, but the things that we worry most about just does not register because we're just not seeing this from. We don't get complement cascade. We don't get these kidney issues that others are getting. We just don't get serious adverse events. So we know what we get at least so far, it's 65 kids. So it's not like we dosed 3. 65 kids with only Duchenne plus we dosed another 6 kids with limb girdle and we know what we get. We get -- in some kids, we get some nausea and some vomiting post infusion, which is resolved by antiemetics, and we got some elevated liver enzymes. We increased the steroids, they very rapidly go back to baseline. That's the profile for our therapy that we've seen, and I think we're very confident that's what we're going to continue to see. One of the concerns people had is, well, historically, you move from a clinical process to a commercial process, there could be changes. And the good news is no. We've dosed a ton of kids. The first 11 that we've shown, and we dosed kids even beyond that. We do not see any of the concerns that others are seeing with AAV9. So I think that seems to be the -- the prime suspect seems to be the vector.

Yes. So just given a really clean safety profile that you've seen thus far and if you kind of collate all of the efficacy data that you collected. Understanding that Study 102 at least that first dose of study may not have met all of the expectations that investors might have hoped for. Is there any chance of discussing with the agency whether or not some sort of an approval could occur at least for a subset of patients even before you embark on your pivotal program?

So not before we embark on our pivotal program because let's be clear, the very nice conversation we're going to have with the division which is going to happen in this summer is going to be about starting Study 301. So we're very clear about this. We are not going to approach any other issues. We're not going to approach a more exotic accelerated approval approach or anything like that. And I would argue, if I was an investor that I would assume that, that's the appropriate pathway for the approval of the therapy, both in the United States and around the world. Now with that said, to your very good point, we have seen what we believe to be very exciting data with respect to the therapy out of Part 1 of 102 where you get the baselines right. Even when the expression because of the titering was lower, than what we'll see going forward, you saw very statistically significant and clinically meaningful benefit in a very short period of time. What I will say is that perhaps after the Part 2 of 102 data comes out, depending on what that looks like, that might form the basis of some discussions with the agency. And certainly, no one will be surprised that Sarepta is going to be as creative and thoughtful about those issues constrained by regulations and science as best as we can be. But I would argue that if I was an investor, my investment thesis would be this company gets 301 going. They have rolled that thing as fast as possible. It's a thoughtful, well-powered study, placebo-controlled. They win the day on that trial, and that therapy gets approved in the not-too-distant future for right now. That would be my primary thesis.

Okay. We have a question that was sent to us just based on a few of the comments that you made. As it relates to Study 102, do you know how many patients had less than 5% expression at the time that you made the last public announcement about the data? And if these do have some patients, who have that level or below, what would the results look like if you were to exclude those patients?

Well, I really got to that sort of detail and we might in the future medical meeting or the like. Broadly speaking, I would say that there are always outliers on both ends. There's a lot of reasons for potential outliers. I mean with respect to 102, there's always the potential that the titering issues created more variability than you would have liked. But beyond that even when you get all the titering right, there's going to be variability. But that variability is going to -- and some of it might be human biology. Some kids just might from a human biology perspective get more special than others. But there's also this other compounding variable, which as you remember, we take the largest organ system in the body, and you take 1 muscle at 1 moment in time and 1 small little piece of that muscle and you do a biopsy there and then correlate it. And so the problem with that, you'll see this, there's a 2018 publication that [indiscernible] actually published that showed that even in a single non-human primate post infusion, you can biopsy one part of the muscle and get 94% and biopsy another part of the muscle and get 9%. So there's variability just from a sampling perspective, and that's why in a very real sense, the meetings become more important than the individuals. But I would say, let's go to 103 as one example. If you take 103, the vast bulk of the patients were near the mean. In fact, the median is right around the same thing it used to be. So there are very few real outliers there. So I think we're getting -- we're rightly a getting a lot of consistency.

Okay. So then...

And again, I would say, even when you have variability in titering like we did with 102 Part 1, we got 28% of mean as a result of that, more variability than we would have liked. When you get the baseline characteristics, right, still all being significant, clinically significant, specifically significant benefit, that's only going to become more -- as the probability of that is only going to increase significantly when you're over here at 55% expression and a very consistent complement titering that tells you that you're going to see that kind of expression on a go-forward basis with our commercial process.

Okay. So you mentioned the next round of updates from 102. So what should we be expecting? And when will that be?

There's going to be a lot of really interesting information. One of the things that people have to remember is, this is not post-hoc. So I think this is really important. Someone might think where you're going to go mine the data down to some interesting additional, no, no, no, no, no. This is a blinded placebo-controlled trial now at least there's no placebo anymore. But it's still a blinded study, and we're going to -- we'll see that at the very beginning of next year. So right by the end -- very end, around at the end of this year to the very beginning of next year, similar to Part 1, we'll have the readout. And so it will be very early next year. That will be 41 patients. So about half of them are going to be -- have been on therapy for 2 years. So we get to watch them. And what we'll have to watch them against is -- we've to watch them against the natural history cohort. Again, it won't be post hoc. We'll build the natural history cohort to align with the patients prespecified before we ever outline and actually get to see the data. So it's very scientifically sound. And then for another group of people, because remember half the people will have been on a placebo, then they don't know which half they are in, by the way. But half of the kids who have been on placebo and then will have intervention in 1 year. So for half the kids we will see something very interesting, which is we'll see their trajectory over the course of the year, and then we'll be able to match that against the -- an age matched trajectory that look similar, and then we'll intervene with therapy and get to see what would have happened in the natural history cohort versus what happened in this case post infusion. So I think that I mean I can say I think the Part 2 data is going to be some of the most robust information around the effect of this therapy in kids with Duchenne muscular dystrophy that exists, probably the most valuable data so far in DMD market.

So just to clarify, will we have updated Western Blot data?

I think we might actually have for some kids updated because they do get a 1 year -- they get 1-year biopsy as well. Because the kids, we have to -- normally, we don't like to do a lot of biopsies on these children. There's bioethical reasons, they are very invasive. That's very -- and the kids we're losing -- the disease is the deterioration of muscle loss. It's not an inconsequential thing to be taking muscle from these kids. But to maintain the blind, you have to have a few biopsies. So you have to do a biopsy, a baseline biopsy of 1 year. So we will get post-infusion biopsies and then 1-year biopsies, which I presume may or may not be available by the time we enhance those results, but it will eventually be available.

Okay. Now that 50-something percent rough level of expression that you're seeing on Western blot, how confident are you that, that is indicative of real clinical benefit?

Very, definitely. I'm a true believer. I break the cool. I'm very confident that this therapy provides an enormous benefit to kids if you can good expression in these children. All of the preclinical models would tell us that, all the mouse models, the treatment models and the like. It's been correlated in so many different ways. You look at the first 4 kids on 101. And now you can look at the functional benefits and they're just looking really late. But you can say, okay, maybe that's a placebo effect, it's just 4 kids. Look at their muscles, right? They not asked third-party data MRI -- muscle MRI study. And those kids' MRI showed that in a short period of time, their muscles left the range of what you'd see the entire range of what you see for a BMD age match kid and went back into the normal range. If you look at the actual -- when you go into the dystrophin itself, it's properly localized to the sarcolemma. So it's right where it's supposed to be to act like a functional shock absorber. It's associated with upregulation of the rest of the dystrophin associated protein complex. It's correlated with the reduction in CK, which is a horrible measure, but it bounces around a lot, but it's a nice just broad indication that something is going on. And of course, looking at those kids in 102, the 4- or 5-year-olds, when you get the ages right, those kids just did brilliantly versus the kids that were on placebo. So you take all of that, that's at 28%. You take that, you're over 50% or higher, where the vast majority of these fibers are being protected by a dystrophin. Remember it's well over 70% of the fibers are being protected, their intensity levels were really high. I'm very confident. What we got to get right is the performance of the study. That's what I got to get this study right. I think we've been thoughtful about that. We're well informed from 102. The Part 1, it was a painful day to have to announce that we didn't get the topline. But when you get past that, you look into the data that has done and there's an enormous amount for us. It's kind of helping us fine tune 301, the powering, the way we look at the kids, the way we look at stratification and the like. I think we have the best possible study available to dystrophin level.

And what are your plans for nonambulatory patients? Will they be included do you think in the study?

Not in 301, but they're going to be -- there's 2 different paths. So first of all, we're already in the process of dosing nonambulatory patients in 103. So it's already happening. So we're going to get very significantly safety and expression from nonambulatory patients. And that's happening, like literally as we speak, quite literally. And then we will have a separate study that will get started soon after 301 as is reasonably possible. So there will be a little bit of a time lag there for a number of administrative reasons, but we'd like to get that study started as well. And so there'll be at least 2 studies that we'll be looking at nonambulatory patients. That's, of course, important to this.

Okay. By how much would your addressable patient population increase if you were to get a label for nonambulatory?

Significantly. It's very significant. It's a significant percentage of kids, I don't remember the exact percent, but the -- but the nonambulatory patient is very significant with Duchenne muscular dystrophy. You could lose sight of this because if you look at some of our 10% kids, they're still walking at 19, but for the average Duchenne kid, you're talking about kids that tend to go off their feet are 13 years old, 14 years old, some much, much earlier than that. So there's a significant opportunity. And more than that, there's a significant need to move fast with the nonambulatory kids. The biggest problem in Duchenne muscular dystrophy is time. We don't have time. We just simply do not have time. And again this horrific disease steals a little bit from the family. And the problem is it steals the lives of these older kids and some of these older kids were not ambulatory. They may not be walking, but they've got the use of their upper limbs, and they are productive human beings. But when they start losing the ability to move their upper limbs and they start -- they lose too much diaphragm, they've got to go on vents, then it's a rapid decline. We got to get to those kids as soon as we can. That's why it was really important to us to get nonambulatory kids dosed in 103. And it's important to us to get that next trial targeted response.

Okay. So let's just think about if both you and Pfizer are trying to enroll patients at the same time, how do you think about picking trial sites? Would you be okay having -- there's always going to be a finite number of sites to pick from. So do you anticipate that you would be overlapping on trial sites, at least some of the time and how would that...

I'm sorry to interrupt. So the answer is we'll have about -- we have more than 30 sites over time around the world, that's our plan. And there will be a number of sites. There will be a dual site. There'll be a site for Pfizer and a site for Sarepta. And I don't think that's it and we already know that. We're well aware of that. I don't think that -- and the reason for that is, of course, that we can get away with not having sites that were overlapping, but there are some very, very important thought leaders and investigators that understand gene therapy very well that are really centers and magnets of excellence for families with Duchenne muscular dystrophy. And so having that site, both the principal investigators both working with Pfizer and with Sarepta, I think, is appropriate. I think the short answer is I don't think that's going to be an issue. For instance, the question is, is that going to be a problem for recruitment? I don't think so. And I say it on both sides, by the way. I think that Pfizer ought not to have a problem with recruitment, either so long as they are able to answer in some satisfactory way, this overhang, the safety overhang that they have. I think that is a big, big issue that they're going to have to come to an answer on in a credible way that's evidenced based. But assuming they can get past that they'll be able to recruit as well.

Okay. So we've talked a lot about gene therapy. Is there anything that I didn't touch upon that you think is important for people?

No I think that's everything with 9001, and I just touched real briefly of course on the limb girdle programs. Those are extraordinarily important as well. We want to start -- we have enough -- what's that?

Yes. Just for gene therapy, was there anything that...

Oh really. No, I think we've hit it all. We're trying to move as fast as possible. We're excited about the next trial to bid for us.

Okay. So let's maybe spend a couple of minutes if we can, on limb-girdle because I think that is potentially one of the more underappreciated programs that the company is running? Can you just give us an update on when the next data update will be for that program? And how you're thinking about the development time line relative to how it's gone for DMD.

So a couple of those. I don't know the next data update. It will be in a medical meeting and certainly we'll be trying taking those decisions. I think you've seen over the course of 2020 that we've gotten really fabulous results in a couple of cohorts that we dosed with our limb-girdle program. The issue now is to get to a pivotal trial. We have prioritized discussions with the agency on that issue until after 9001. So really, right after we get going on 301, we want to get into the divisions, it's the same division and start talking about the pivotal trial for 2E. That's a very different issue for us. It's not -- we don't believe that this will be the subject of our discussion with the agency. We don't believe that we should have to do the kind of trial for 2E that one is doing for 9001 in DMD. This is an ultra-rare disease with 2E. It is the native protein. So there really is no credible argument for whether or not the resulting protein is functional. It's the actual native protein it goes for. We're seeing extraordinarily high expression as you know, very, very similar to what we see with DMD given that we're using the same promoter and the same capsid. So we're going to -- the big discussion with the agency is we want the leanest possible approach to limb girdle Type 2E and that approach from our perspective ought to be on a model. So that's going to be a discussion. Whether we're going to win the day on that, there are -- it's a great, not binary, it's more -- there's more grade to that issue, but we're going to go in with an argument that we ought to see something on a biomarker to be able to do this very rapidly. And if we can do that, it will be a marker for the rest of our limb girdle. And the interesting thing is we talk often about having 5 programs. The reality is we now have 9, some of which we don't talk about, but we built constructs for 9 of the limb girdle's total. And so this is an enormous opportunity. And limb-girdle together is an opportunity to do good, but also it's -- from an epi perspective, is approaching the size of DMD in all of these programs. So this is extraordinarily important for us.

Okay. So with that, we'll leave the conversation to continue at a later time. Hopefully, we'll get to talk about the rest of what's going on at Sarepta. I wanted to say thanks, Doug, and thanks, Ian, for joining us this morning. It's always good to catch up. There's obviously a lot to look forward to in the second half of the year, and we hope that all the interactions with the agency are going to go well.

Thank you very much.

Thanks, guys.