Sarepta Therapeutics, Inc. (SRPT) CEO Doug Ingram Presents at Cowen 41st Annual Health Care Conference (Transcript)

Sarepta Therapeutics, Inc. (NASDAQ:SRPT) Cowen 41st Annual Health Care Conference March 3, 2021 2:40 PM ET

Company Participants

Doug Ingram - Chief Executive Officer

Conference Call Participants

Ritu Baral - Cowen and Company

Ritu Baral

Hey, everyone. Thanks for joining us at the Sarepta fireside chat at the Cowen 2021 Health Care Conference. Hopefully, our first and only virtual health care conference for Cowen.

With us from Sarepta, we have CEO, Doug Ingram; CFO, Ian Estepan; and CMO, Gilmore O'Neill, who I'm sure most of you know.

Question-and-Answer Session

Q - Ritu Baral

So, Doug, let's get started. I guess, Doug and Gilmore. So the last major milestone you have is the top line for the Phase 2 102 study from your DMD gene therapy. So you missed on the top line NSAA analysis, because of some pretty significant baseline imbalances between age cohorts, which were not stratified for baseline lock.

One question I've gotten from investors is why didn't you stratify? And if you could from there, just tell us how you're doing? What's the latest from the crossover patients and how they've been treated?

Doug Ingram

Yes. So a couple of thoughts on that, and you're going to hear a hint of defensiveness I suppose in this question -- in the answer to the question. Look, Sarepta has an enormous amount of experience with the knowledge about Duchenne muscular dystrophy.

And it actually was us that had signaled that in this -- what would have seemed like a fairly tight age range, four to seven years old, there would basically be two populations, a four to five-year old population and a six to seven-year old population.

And I think you know that Ritu, because we've talked about this many times in the past about that. And that's why we built, not only to make sure that we stratify it by age, four to five and six to seven, but that we would have separate analysis of the four to five and six to seven.

We had not anticipated that, well, even within those four to five and six to seven’s, that there could be this sort of imbalance. It was, I will point out, extraordinarily improbable that this would have occurred.

The P value, as I've mentioned before, the P value on the baseline characteristics in the six to seven’s, between those two groups was 0.004. So this shouldn't have occurred. It should have been -- only four times out of 1,000 should this have even occurred. And then in the worst possible way for the study, which is, all of the severe kids were on therapy and the mild kids were on the placebo.

So what we ended up having in this trial ironically, we knew we would have two patient populations. We ended up with three patient populations and that made hitting the top line impossible, because the six to seven’s were certainly, but now I will point out, now I'll get onto the crossover for a second.

I will point out that when you get the baselines right in the four to five-year old age range that with 16 kids we strongly hit statistical significance, 0.017, and a very clinically meaningful benefit over placebo in only 48 weeks, in heterogeneous population in a degenerative disease that's always had its challenges, for the first time ever in the history of Duchenne muscular dystrophy that we’ve seen these sort of results on NSAA in this kind of DMD population. So we're excited about that. We did miss the top line because of the imbalance.

All that defensiveness to one side, I want to be very clear, we are not going to have this happen again. We're not going to rely on just good luck in the next trial. So we will make sure that we are thoughtful about stratification, I like to ensure that the baseline characteristics for the next population are in good order.

Now on the crossover case, the good news as you know is, by the time we’re at JP Morgan, all of those kids had then dosed. And then, of course, those people should remember is, this is an interesting study, Study 102. That result that we provided in January was only part one of the study. It's still blinded. And in fact, it is quite a debate internally I will say and I will give Dr. O'Neill enormous amount of credit for his pushing in the direction of ensuring that we kept that blinded and did a two-year look as well. That's ongoing. It's going well. And all blinded by the end of this year, we had last patient, last visit and then we'll have some really interesting data on a Study 102.

We'll have some kids that will have been on therapy for two years and we'll have some kids that have had an essentially 48 weeks, but have had essentially one-year run in to watch their trajectory and then we get to intervene with therapy and see what the therapy does versus the trajectory. And we can look at all of that, also gets [Indiscernible]. So, it remains blinded. It's going well. Its executing and we should have that data essentially by the very beginning of next year.

Ritu Baral

Safety and tolerability in the post dosing time period has when we bought that, Doug?

Doug Ingram

Yes. Let me be clear, the study is still blinded. So, if you ask very specific things, I won't have them. I will say broadly speaking, as we saw in the 102 Part one; we are seeing a very stable safety profile. We know what we are seeing and we have seen nothing different thus far in the cross-sell for patients.

So, we feel very -- we feel increasingly confident that we understand the safety profile of the therapy at these doses. As you know, we see some elevated liver enzyme. We don't see the things that are particularly troubling. We don't see clinical complement manifestations ranging along those lines.

Ritu Baral

So, nothing outside of the already characterized profile?

Doug Ingram

To the best of my knowledge.

Ritu Baral

Okay. So again, some of the investor pushback has been on the fact that -- or it's been on the topic of, if this therapy provide a truly clinically meaningful benefit. The baseline on balance wouldn't have mattered that those five or six-year old -- the five to six-year-old would have caught up to the naïve, the treatment naive patients and it would have sort of closed the gap even if they were sort of outperforming almost normal. This therapy does not normalize patients if it's too late.

Doug Ingram

Yes. That is -- so I'm going to be clear. That is mistaken. I say that in kindest term. That is a mistaken view. It would certainly be the case that that is true over the long-term. This is a long-term degenerative disease. So, I will readily agree if that's the case, if you look at it over a long period of time.

But looking at it over one year, there's no chance that that is the case. I understand so like in data we have much more granular data than this. When you look at like the external data set and you benchmark against this age range and this NSAA.

For the treated group, it was so severe that you could have envisioned those kids going down three or four or more points over the course of 48 weeks. You compare them against an entirely different we did. We compare them against an entirely different population of kids, who are mild and actually were going modestly up over the course of this year. This is not about the profoundness of the therapy. If indeed those kids in the six to seven-year-old age groups should have been going down four or five points and were stable over the course of this year, those kids benefited as well as the four to five-year-old undoubtedly and that would make sense for a mechanism of action perspective.

And this is also not about the size of the study. We would have had 3,000 kids. If you treat -- you compare essentially fundamentally different population, there's just no way, you can tease out in this short period of time, a statistically significant difference regardless in the profound of the therapy. And there's no way around that. I mean, this would be as if you took essentially in one regard, age is a very important marker, but it's pseudo specific. It's not enough.

And so all of us would now, you couldn't compare a six year old to a nine year old. No one would expect it. Because you said it's not profound, because why is this nine year old not doing as well as a six year old, we would all think that's absurd. And that is essentially at least qualitatively the argument here. These kids are so -- the delta between these kids based on are so different and trajectory is so different that you just -- you are -- it match the value of the therapy that's -- oh, that's great, but of course it's on us to the fact that the baseline characteristics were different and we'll address that for the next study.

Ritu Baral

So all that being considered and the strength of the four to five patients subset being considered, what are the chances the FDA is still going to let you file for accelerated approval on the micro-dystrophin surrogate?

Doug Ingram

Yeah. So I don't think anyone that knows – I would imagine that we're not thoughtful and creative that we won't have broad-ranging dialogue with the division. But I do think from a planning perspective, I think we should all assume that the next study is going to be the basis for our approval both in the United States and around the world. I think that's the most reasonable highest likelihood approach. It doesn't mean we will not have discussions. It doesn't mean we're not going to go to the agency and show them our data and the benefits that we've shown we've seen in the study for the four to five year olds. But I think for all of our planning purposes if I was as an example an investor and I was making some decisions, I would presume that it's the next study that's going to be the basis for.

Ritu Baral

Got it. Is there still data that you could generate that would -- is it possible that the crossover extension Part 2 of 102 could generate data, especially since you mentioned last night on the earnings call -- last night, days are running together, that you're going to be expanding 103 more four to five patients?

Doug Ingram

Yeah. Well, a couple of thoughts. So without directly addressing the regulatory issue, I will say that first understand the following, between 101 and 102, we already have far more insight and a far more advanced view of our therapy and the way it works and it -- and confidence in the therapy than anyone else could further along than anyone else in that regard. At the end of this year, we're going to have an enormously valuable piece of information, a set of information, two-year data, trajectory analysis, analysis gets natural history. I mean, quite apart from what that might do from a regulatory perspective, it is going to be a profoundly important moment in the understanding of micro-dystrophin and what it does to children with Duchenne muscular dystrophy across these age ranges.

I would say as it relates to the 103, the 103 study to remind everyone is this study that's looking at the commercial representative material, the process we used to commercialize the therapy. And we're going to look at both -- it's really not function related issue. We're looking at expression and safety. We'll have that data in the second quarter from our first cohort.

But as you've rightly noted, we have -- we've expanded the size of that study a little bit to ensure that we have a nice balance of four to five's and six to seven's, but it doesn't slow us down. It doesn't slow us down either in releasing the data from the cohort, the first 11 cohort next quarter does have any impact later on that convention at our next study.

Ritu Baral

Got it. How do you right now look at the relative strength of your gene therapy compared to competitor gene therapies that have kicked off clinical data? And what do you think that might mean for competitive enrollment across the Phase 3 programs?

Doug Ingram

So I'm going to be careful everyone knows that – tend to unnecessarily competitive, but I will just be actually accurate. We have always been extraordinarily confident in our therapy. Dr. Louise Rodino-Klapac in concert with Dr. Jerry Mendell have been working on this and building this construct and testing this construct long before we ever got to patients for some 14 years.

We've always believed our therapy was differentiated in really every regard safety, expression and then ultimately function, even from the preclinical models have they looked at all of these constructs. And then we're in a place right now where nobody has the – no one's done as much as we have no one's been able to confirm the proof-of-concept that we have both in Study 101 and in Study 102. So I will readily admit, Ritu that I am biased. I am the CEO of Sarepta, but I do think that we have – we have a highly differentiated therapy with a strong proof-of-concept.

You know, if you look at Study 102, there's two-ways to look at that part one data. The first one is, of course, very disappointed that we didn't hit the primary endpoint. Well, although, we know why – but why are we disappointed about that, because we hadn't had this hope that we could maybe use that as a bracing strategy to accelerate this therapy quickly.

But if you put that to one side and recognize that this means it will affect a 12-month or so delay. Putting that issue to one side, as a proof-of-concept, as a Phase 2 is brilliant. We have done something that no one else has done. We've shown -- if you look at the four years to five year olds in 16 kids strong statistical significance, strong clinically meaningful NSAA.

We have more insight out of that study than anybody could have right now because of how advance our approach is. And frankly it's going to inform Study 301 in ways that I think are going to be unmatched. One of the things that others have done and I think it was wise of them frankly. They – others that were looking at using forms of microdystrophin looked at Sarepta as the leader and said, we're going to essentially replicate what they did.

And so they essentially – Pfizer's example really basically replicated their study off of 102. We have the opportunity to really look at what's coming out of 102, adapt our thinking to 301 and then get 301 started this year and hopefully, we rolled this out as possible there ever. So I think we're -- I remain, confident that our construct is highly differentiated and our program is highly differentiated.

Ritu Baral

Going back to the 103 extension for a second, have you actually treated like patient 12 and 13, or are you still -- or is that going to happen?

Doug Ingram

It is going to happen. I don't think we'd yet dosed the next cohort.

Ritu Baral

Does that mean we can still get all of that data all together in Q2 including -- patients?

Doug Ingram

No, no we're going to get the first 11 in Q3. That is gong to be a little bit delayed yes.

Ritu Baral

Got it. Okay. Got it. When are you going to talk to the FDA about the Phase 3 design? And when are we going to know? Are you going to tell us investors at the time of trial initiation mid-year, or are we going to get it beforehand?

Doug Ingram

You'll get it at around the time of trial initiation.

Ritu Baral

Okay.

Doug Ingram

So, they've got a lot of work to do. The thing that – the thing you have to do to have a meeting with the agencies you have to have the data in front of you. So the first thing we have to do is complete our analysis of 102 -- 102 Part 1. And you might think that – and we've done that to a significant extent. But there's a lot of insight out of Study 102. So we need to really make sure that Study 301 protocol is fully informed by that.

We need to get the Study 103 first 11 patient data right, to have that conversation with the agency we have to have the data of our expression and safety out of Study 103 and then we'll have the meeting do the briefly broke out the conversation with the agency. And then assuming either way then we will shortly thereafter communicate to the community where we are with the study. And of course, as you know our goal is to start that study somewhere around the middle of this year-ish. And the goal is to try to get all those kids dose as fast as possible with the aspiration of getting all just by the end of this year and that's at least our current goal.

Ritu Baral

So we have a question in from a client on the webcast. I'm trying to better interpret it. Do you think that your -- basically your label indication will be limited by baseline entry criteria. So like if you -- do you decide that you're going to go with a certain 6-minute walk baseline or NSAA baseline, are you going to limit your market upon any eventual approval?

Doug Ingram

Yes. I think that would be -- I know -- let me start with that no, that’s shift -- that is not our – that kind of goal is moreover I think there's no any logic to that and it shouldn't be the case. And the reason for that is straightforward. The reason that we create -- we try to create very rigid guardrails around entrance criteria is because we're dealing with a heterogeneous degenerative disease and so that the benefits of that therapy can be seen in a short period of time.

To the very good question you asked earlier in the conversation, over a long time it will all come out. If we wanted to wait seven or eight years, we would see the benefits of this and we could be far more – foremost restricted in the approach. But I think the agency would understand that the goal of creating a very strict guardrails around entrance criteria is to ensure that you have a very well matched patient population, so that when there's a benefit, you can see it. That's been we’re seeing the hard way like, what happens when you don't have good baseline match the 6 to 7. I am completely convinced that the 6 and 7 is benefited from the therapy just as much as the 4 to 5s.

But when you compare them against the whole group, it gets hidden. And so that's the goal. So it shouldn't affect the label. And our goal in with this -- the goal with all of this is to get to the broadest label possible, consistent with the data and consistent with the mechanism of action of micro-dystrophin.

Ritu Baral

Got it. And a follow-up to that one before the next question would work. Client have not finished, the second half of your question is coming. Do you have information on detail right now regarding the improvements seen in 102 like skill gains refinements of like certain movements etcetera, or is that something we're going to get at MDA?

Doug Ingram

If you won't get at MDA, there will be no -- essentially no new data in MDA. There is some medical presentation on 9001 Part 1or 2, but you’ll there's nothing significant and new.

Ritu Baral

Okay. Nothing new out of the 102 data that you’re going to be putting here. But will we get more granular from skills gained after that?

Doug Ingram

Maybe, early next year, but not -- for the time being, no. I mean, what we are doing and we can -- we have a lot of data. We have patient level data. We have all the composite. I wouldn't say it’s a composite. We can break the composite down, we can time test. We're not going to provide a lot of additional data there, what we're going to do is use it to inform 301.

Ritu Baral

Okay.

Doug Ingram

That's what we're doing right now.

Ritu Baral

Got it. Another question in -- based on the data set that you have right now, what's your confidence that it will work in older patients? I'm assuming, client means over seven maybe 10-ish.

Doug Ingram

Yes. Well, look, I mean, we are confident. I am confident that the mechanism of action of SRP-9001 would indicate that, that will work across all parts of the patient population. We know what DMD does, and I'll explain what we have to do to get there.

We know what causes Duchenne muscular dystrophy. These kids are missing the structural shock absorber. Dystrophin -- microdystrophin replaces that with a functional -- a much truncated but a functional version of that dystrophin gene for us. As long as the kid has muscle, cardiac muscle, skeletal muscle, diaphram muscle, they should benefit from the intervention in the microdystrophin regardless of the age.

Now, there is a separate question for the older non-ambulatory kids as well, which is we have to make sure that we -- we would have to dose them and we have to make sure that we have the right safety profile for them. And so that's a separate exercise.

But from a pure mechanism of action perspective, we are confident that microdystrophin ought to benefit all kids across the spectrum. And then, no kids should be essentially off the table.

I mean it is for that reason -- sorry to kind of go on. But it is for that reason that I find it -- is basically silly to envision that in the 102 results, we see brilliant result in four to five. And for some reason it just -- on your seventh birthday, it just stops. There's no scientifically valid hypothesis that could explain that.

What does explain it is, we frankly didn't get the right comparator population. So that's our view. And that's why -- and if you believe that, as we do, then of course, that's why we got to fight to get the broadest set possible, so that we can intervene with these kids across the entire spectrum.

Ritu Baral

How are you thinking about your limb-girdle studies in light of what happened in Study 102? I mean, I know it's a different therapy. I know it's a different indication. But you picked the subset of limb-girdle to act like -- because it acts as severe as DMD.

Doug Ingram

Yes. So, there's a couple of thoughts on that. One of course is, all of the building data that we have, both in 2E and in 9001, gives us confidence across this approach to gene therapy. So, we're excited to ever at our ability to create robust expression to do so in a reasonably safe ways that we don't have things like complement. We're confident about the promoter, all of that’s shared across 9001 and 9003 with capsid and promoter.

But if 102 tells us anything, it reconfirms the view that we have with respect to this very rare disease, limb-girdle Type 2E, which is, this idea that you can do a traditional placebo-controlled trial on a 2E population I think is mistaken. And I think if we didn't understand that already, which we did, you would understand even more on that.

So, I think that's going to be the really important discussion that we have with the agency. It's a much -- it's a far rare disease. It is a -- the native protein. We're making a robust amount of it both in our low dose and our high dose cohort, and we're doing so in a reasonably safe way. And so we should have a very lean approach to that development pathway. It shouldn't include from our perspective for instance the approach that we're taking with DMD, it should be much leaner. But we have to have those discussions with the agency before we're confident that we're alive with the division on that.

Ritu Baral

Got it. I just want to ask you about -- yeah let me just spend a few minutes on your pipeline and what do you -- Doug what's your favorite program from the rest of your pipeline outside of DMD, what's your favorite gene therapy or otherwise? And then talk to us a little more about, how you were thinking about gene editing in DMD?

Doug Ingram

Yes. So, a couple of things, I mean, one of the things you're going to find from us over the course of this year is this razor-sharp focus. So, you're going to surprise you that we have over 40 programs and I keep hammering on about our top priority, which is a AMONDYS, EXONDYS, VYONDYS, 9001, 9003 in the group. So, in that regard, I almost don't want to discuss the rest of the pipeline, because I want to keep everyone focused.

I think there's a lot of exciting things in our deeper pipeline cardiomyopathy and some other really interesting approaches. Probably, the most exciting next-generation element in gene therapy beyond just the disease areas that we're working on is the ability to actually to make what we do even better over time.

And so the things that I think are going to be really exciting over time is empowering re-dose, right, knocking down pre-existing neutralizing antibodies. We have programs in both of those, both internally and with partners, finding down the road and this is more much more of a research project for now, but I think it will be important for the long run.

Down the road, either getting even more advanced and improves, viral caches, either immune abating, liver abating, better tropism or moving to even new modalities. You know, we have both exosome and lipid nanoparticle as approached. That's much more research-oriented. In fact, to me is a really exciting area of research, and we want to play a significant role, if not the leadership role in that.

Overall, on gene editing, we're -- look, we're really excited about the conscious of gene editing, and for neuromuscular neuro and beyond. We have a Gene Editing Innovation Center in Durham, North Carolina. We started building that out some time ago. We have I think one of the world leaders in the application of CRISPR/Cas9 and gene editing to the neuromuscular area. And that's of course Dr. Charlie Gersbach from Duke and he's building a team around him right now even as we speak.

I think gene editing is going to be -- it's a little bit more down the road than gene therapy. Gene therapy is right in front of us right now just like RNA, but we're really excited about gene editing over time. I think there's a lot of questions that have to be answered along the way.

I think one of the really interesting questions that has to be answered with respect to gene editing is do we use viral capsids? Because right now, it's all viral capsids just like gene therapy or if you're going to deal with something like gene editing, do you need to over time evolved into lipid nanoparticle or exosome or something along those lines. But that's still in the research phase, but we've got some really exciting work going on with some really great scientists working on.

Ritu Baral

Have you seen anything in the data thus far that sort of -- that's sort of pushing your interest in re-dosing and technologies that enable re-dosing, or is it other people's data?

Doug Ingram

It's the data of our partners, right? So we've got two different approaches, right? We have an approach that, you could co-administer with the therapy that would essentially hide your gene therapy from the muscular that would make neutralizing antibody and that could be empowered dosing.

And we've got another technology with a partner. I'm not going to mention either works, get confused and an embarrassment of today. And we have another approach where we would knock down essentially ablate neutralizing antibodies to either dosing people that have pre-existing neutralizing antibodies or hopefully, potentially, knocking them down to empower redosing.

And then, we have some other – we also have apart from that, it's more just all internal. We have some other internal approaches as well. We've done some interesting non-ambulatory work that we haven't yet disclosed that gives us confidence. And I will say this, and I think that, the confidence that we have to probably share by everyone in gene therapy.

It's important that we get to a place, where we can knock down pre-existing neutralizing antibodies. I think that's at least for us about 15% or more in some other viral capsids vectors, it's going to be even greater percentage of gene therapy will be off the table until we do that. And even more important, perhaps even than that is through re-dosing and we remain confident that, we all as a biotech industry, we will solve this issue, and we will get to a place where we can start re-dosing over time.

Ritu Baral

Great. All right. We're just a minute overtime. Doug, thank you so much. Gilmore, thanks for joining us, Ian as well, really appreciate your answers. And looking forward to both the 103 data, as well as an update on the Phase 3 design in that start.

Doug Ingram

Yeah. Thank you very much. And don't forget our launches. We just got our launches approved.

Ritu Baral

Yes. Sure. I completely ran over, actually approved and strong product. But we will get to that next time. Thanks.

Doug Ingram

Thank you so much.