Solid Biosciences Inc. (SLDB) Earnings Call Transcript & Summary

Good morning, everyone. My name is Gena Wang. I'm SMID-Cap Biotech Analyst at the Barclays. Welcome to 27th Global Healthcare Conference, and today is our last day. It is my great pleasure to introduce our presenting company today, Solid. On the stage with me, we have Gabriel Brooks, Chief Medical Officer. We also have Bo Cumbo, President and Chief Executive Officer. So, before we dive into the questions, Bo, maybe you want to give a quick high-level overview about the company.

Yes. Thank you, Gena, and thank you, Barclays, for having us. So Solid Biosciences Precision Genetic Medicine company, very exciting year for us in 2025, truly almost a transformative year for us. [Technical Difficulty] released new data on our next-generation Duchenne drug called 003. We have an IND open, and we'll be dosing patients for Friedreich's ataxia. It's the only dual route of administration trying to treat all the different manifestations of Friedreich's ataxia by replacing frataxin. We should be dosing patients later this year. We're close to filing an IND for CPVT, Catecholaminergic Polymorphic Ventricular Tachycardia. That's an arrhythmogenic fatal arrhythmia mainly seen in children. And we'll be filing that IND first half of this year. We have capsids now, and part of our study that we just released with our data that we just released with 003, that's our Duchenne drug, was really almost 2 studies in 1 because it was not only for Duchenne, but it was also our capsid. It's the first time this novel capsid had been in humans. And it looks very unique. It could be the best cardiac and skeletal muscle capsid ever dosed in humans. And so, we have this capsid library, and then we're looking to file another IND in 2026 for TNNT2, another cardiomyopathy, and we'll be continuing to look for other opportunities to build out. So, it's a very exciting little company, and that sums it up.

Okay. Great. So, maybe we will talk about DMD data. Recently, you presented very comprehensive and impressive data, and I think it generated a lot of excitement. So maybe walk us through. I think one part is it's also very consistent. I know it's only 3 patient data, but was very consistent high-level expression, and you did have a lot of measurements showing the consistent potential clinical benefit. So maybe tell us maybe the next step and what's the status there in terms of the patient enrollment. With current data, I'm pretty sure you're also communicating with the patient-doctor community. How would that help you expedite your enrollment process?

Yes. I'll tell you what I'll start it off, and then I'm going to kick it over to Gabriel to go through all the details and the next steps. What was important to us in our Duchenne program because there's been a lot of noise in Duchenne over the last couple of years with microdystrophin, particularly is we wanted to understand and make sure that we had confidence that once we saw certain markers, it would give us confidence that if Dr. Brooks sets up a clinical trial, very thoughtful strategic clinical trial that is unique compared to others, that it would give us a lot of confidence and give you and your investors a lot of confidence that we will hit ultimately P-value or change the lives of these children. So, to us, it was not just about protein. You and I have talked about this in the past. A lot of people just talk about Western Blot or Mass Spec, but it was this cascade of events that led us all the way down to muscle integrity. We spent a lot of time looking at not only raw protein but positive fibers, Beta Sarcoglycan complex coming together, biomarkers, both acute and chronic muscle damage biomarkers. Then, once you understand those 2, then it leads to biomarkers of muscle maturation. All of that led us to believe that we have the best-in-class drug, one that will change the lives of these little boys, and that was the goal. But I'll turn it over to Dr. Brooks.

Thanks, Bo. So, Gena, to your question about what the next steps are, I'm really actually quite pleased to say that we've already taken a lot of additional steps. In fact, we presented those 3 participants, but I'll share with you and remind your listeners that, in fact, we've already dosed 7 participants. So, we've over doubled the number of participants. And so, there's those brave boys are accruing data that we're really eager to look at ourselves. As you know, we've been very disciplined in terms of really only analyzing the data when we feel we had a sufficient data set so that when we come to you and to the Street, we're presenting something that can be interpretable, not just kind of one-off data. What we're planning on doing, as we've shared in the past, is once we have around a dozen participants worth of data that have reached 90 days, so getting that 90-day biopsy, we're then really eager to engage with our partners at the FDA and discuss with them the pathway for registration, based on that data set as well as we're expecting probably a data set in totality, close to the size that we know our colleagues in the field, REGENX has shared around 20 to 30 participants. So, when is that going to happen? When is that conversation going to happen? When is that 10 to 12 patients; that's going to happen in the second half of this year. I know we're all eager to see the progress of this program that has shown peerless data. They're without peer in terms of the level of microdystrophin, the amount of positive fibers. Then, Gena, I think it's really important. Microdystrophin it's an integrity protein, but it also binds partner proteins. This is the only microdystrophin that's ever been shown in patients to actually recruit Beta Sarcoglycan and nNOS in patient clinical data. I think is really important in terms of trying to address the biology that's abnormal with Duchenne. So, that's our program in our next steps. The only other thing, and I'll stop, is that we are starting, and we've shared this as well, our Phase III pivotal trial in the rest of the world this year. So that next half of the year, as both said, this has been a transformational 2024, and 2025 builds on that with the kickoff of our registrational Phase III double-blind, randomized, placebo-controlled trial in the rest of the world, which will be the confirmational study for the study of accelerated approval in the United States.

Okay. Super helpful. So maybe talk about the additional total 10 to 12 patients, right, enrollment. You already enrolled 7 as of February 17, which like 3 to 5 patients. I think you previously you said mid-April. We're only 1 month away. How's the status there?

Wonderful. The boys are doing great as we hear. We're not in contact with them, but as we hear from their providers, this is such a wonderful space because we deal with these physicians that really have ownership of the patients, meaning they really want them to do well. It's quite thrilling to be in a position where, in that partnership, we're hearing such good news coming from the clinics about these boys doing well. So, the boys are doing really well. In terms of interest, Gena, we talked about this. You had a fantastic panel that I was privileged to be a part of the other day, and we talked a little bit about this. These boys and these families are quite brave coming in, and whether it's with REGENX or for us, participating in a gene therapy trial and you have to ask with commercial drug available, why would they do so? I think they really want to look for something that can address more of their disease than what they're seeing. And so, we hadn't shared any data with anybody, and we still had lots of families that wanted to be a part of that. Now after we've been able to share our initial experience, it's hard to call it data. It's only 3 patients, so we'll call experience. We've shared our initial experience with the community. You can only imagine how overwhelmed we are right now with interest, which is great. And so, we really feel almost a moral need to really ramp up our dosing and be able to meet that demand.

So the extra 3 to 5 patients, like are you on track to complete this enrollment mid-April?

Yes. I'm just going to reiterate what Gabriel just said. We had to wait to release the data before we could sign a lot of the manufacturing contracts that are now signed. I mean the data is so good that we feel very confident. And so, we signed all the manufacturing contracts. If we would have gone at risk and we had all kinds of drug right now, we would literally fill this trial by end of May. The demand is so intense to get into the trial. And this goes way back, Gena. I mean, even pre-data and Dr. Brooks just sort of touched on this, obviously, there was a drug that was already on the market. A lot of people were questioning, would there be interest in a next-generation Duchenne drug when there's a commercial entity? The answer was yes. Clearly, we had dosed 6 patients before we released any data. And now the demand is such that if we had all the drug in the world, we could literally fill this trial by May. We're in the process. We just signed all the contracts after we released the data and in the process of making thousands upon thousands upon thousands of liters of material to fill the trial. And we're on track, 20 patients by the end of the year, 30 patients by the end of Q1. And we believe we're very hopeful that, that will be the trial that we need for accelerated approval. We have to speak with the FDA. Obviously, we're going to do that later this year. And if we get the same treatment that REGENX got, and we're very hopeful that we do, then that's going to be the trial. And then Gabriel already said, we'll have a confirmation trial up and running ex U.S., too.

Sounds good. Since you talk about ex U.S., I think you total have 6 sites, 5 U.S., 1 ex U.S., right, Canada?

That's right.

Canada. So, what is the plan? And then also I just want to make sure, like right now, you don't have any waiting period. You can enroll as fast as you want, right?

Yes. So, there's a small subtlety there. We, in our older cohort of boys, 7 to less than 12, we are just emerging from Sentinel dosing. So, we can go parallel dosing with them very soon in the younger cohort up to 7, the 4- to 7-year-olds that can be done in parallel. One small detail about next steps that I think may be of interest to you and the community is that with the kickoff of our Phase III study in the rest of the world, we actually are obliged to have a plan to study SGT-003 in age 0 to 18. And so, we are engaged in doing that. And I think, yes, we're going to fill this Phase I trial in the U.S. and Canada, mostly with that kind of 4- to 12-year-old, but we are going to be starting to dose in that younger cohort of 0 to less than 4 as well.

Yes. I think that's important, Gena, because I know I read somewhere that we weren't focused on the younger kids, and that's not true. We had to step process into the younger children. We're there now. And so that we'll be dosing 0 all the way to 18 years of age.

So then for the, okay, so 7 to 12, you're just emerging sentinel dosing, so you can dose as fast as you can.

Correct.

And then you are not planning to dose higher than 12, right, for the pivotal study?

We will be, I think, but in terms of we're concentrating on that 7 to 12. And Gena, I'll be very honest, the reason is because what is of interest, we believe to the agency is not only are we showing really the significant microdystrophin expression, we can show biomarkers, but also that there's some signs of clinical benefit in there. We're focused on ambulation, okay? And so, by focusing on ambulation, by focusing on time to rise, we're really picking, we're trying to emphasize that patient population where they're still ambulatory, but we know we're starting to see they're having difficulty. And so, we're really honing that population and emphasizing that in terms of our data set so that when we come to the agency, we can all look at the data and feel very confident of the effect.

So for the 30 patients, mainly is 4 to 12 and you will not dose beyond...

That's correct.

Outside of this age range...

4 to 12. 4 to less than 12. And I want to say we are committed to those older boys.

So that will be a Phase III study.

Separate cohort, yes.

Yes. Okay. Sorry, Phase III study, separate cohort. Right. So, the Phase III study, sorry, so the Phase III study, like you mentioned to 18 age. So maybe the exact age confirmatory Phase III, what is the age?

Yes. So again, that 7 to less than 12 years of age, ambulatory boys that have a predictable decline. Look, this field is really, we are really in a privileged position because we've had groundbreaking work done by the first-generation gene therapy. And we've learned a lot of lessons. And we cannot repeat the same mistakes that occurred and led to- we believe that contributed to the negative trials of CFRIO and EMBARK. We just can't do it. We need to make sure that we're really thoughtful. So that's exactly what we've done. We've looked at those studies. I believe that ELEVIDYS is modestly effective. And the fact that they were dead neutral, not able to show any clinical benefit, that's not something that; we needed to learn from that experience. So, we looked at that trial, and we believe that we can have a more effective, a more efficient trial. We've also been working with our partners around the world, looking at their data sets. And from that, we believe that we have a very efficient trial for a double-blind, randomized placebo-controlled trial in that 4- to less than 12-year-old range looking at very specific inclusion/exclusion criteria that's broad but focused.

Right. So, going back to both comments, separate cohort, 0 to 18 ages, what size will be that cohort?

I think that right now, we're gaining experience with those older boys. It's too early for us to really share how the designs around looking at upper limb function and the cardiomyopathy. I think the very exciting potential signals that early experience we saw with the heart for those first 3 compel us to think about how can we look at potential benefit to the heart. We need to look at that. But Gena, I wish I could sit here and tell you I had a design ready to go. We're still looking at that data.

So just like a rough idea like 10 patients, 20 patients for that separate cohort. So, like zero to 18 patient cohort, yes, how many patients you are thinking? And then the purpose, I'm pretty sure you wanted to have a broad label potentially. And how many you think that will be sufficient to serve that purpose.

Well, we know that ELEVIDYS got an accelerated approval for 6 patients' worth of POL data. And so, I think we want to have a data set much more robust than that. So maybe we can leave it there.

Okay. That's fair. Okay. And then also I think we're talking about the sites, active sites. So, like one part, like do you think also -- like any plans on how many sites you wanted to activate for the pivotal study, do you need additional sites in order to...

We're opening in the rest of, it's really a rest of the world study, for the pivotal study.

Yes, pivotal and then Phase III will be the next step.

So we have such demand with the partner sites we have, and we have demand to get into the study as centers. So, we are expanding the center, I think, the center list, but I don't, we don't really need to have a vast, much more than the 6 that we already have. So, I think we can say half a dozen potentially new sites coming on board. But we need to be parsimonious because we're getting such demand. The last thing we want to do is to go to a site, work with them, get them ready to go and say, it's closed because we've already dosed all the boys that we need.

I see. Okay. So likely existing sites?

Existing sites...

Yes. So, like we talk to some doctors, they have logistic capacity. They can only treat one to 2 patients per month, but those for the commercial. So here, I...

I don't know if that's, I mean that's a broad brush, right? If you're having SAEs, if you're having events, then they have a governor on the amount of patients they can.

I think for them, maybe it's because all the logistics -- the insurance would take like several months. So, in your case, like all the sites you are active now, do they -- like how big is the patient pool? Are they also treating the -- providing the commercial drug to the?

Yes, of course. But the patient pool, I mean, this goes back to my comments earlier. The patient pool is one big, very large, not only in the U.S. but ex-U.S. There's a lot of patients that want to try other therapies, including outside of gene therapy. And so, they're lining up and the physicians are very thoughtful about which ones to put them on. So, there's plenty of, I mean, we, like I said before, if we had all the drug right now, we could build the trial by May. There's plenty of demand.

Yes. Okay. Good. And then next step, Okay. Yes. Okay. You already mentioned that. We have a few more minutes. You do have a tons of other programs. So maybe talk about the CPVT, the R&D of first half '25, the steps to submit the final steps to take to submit the IND, where you are. And then maybe if you can share any initial thoughts on the clinical trial design.

Yes. Before I go to CPVT, I want to talk about FA because of course, DMD and FA is really a one-2 punch, you don't see many companies that have 2 different types of drugs like this that can really change entire patient populations and diseases like this. So, FA, we'll be dosing the IND is open. It's the only dual route administration for not only the CNS but cardiac manifestations of the disease. We have sites lining up to be participating in this trial, and we should be dosing patients second half of the year and then hopefully reading out those 3 patients in the first cohort first half of next year. And I think that that's really important because you have a one, 2 punch in Duchenne, meeting with the FDA later this year in Duchenne, coming out of that, reading out the 12 patients or so, 10 to 12 patients worth of data plus giving an update there, starting our confirmation study in ex U.S. and dosing patients in FA, the only dual route administration drug treating all the manifestations of disease, announcing that first half of next year. CPVT, the only drug of its kind for CPVT. IND is going to be filed first half of this year. We're almost halfway there and we're going to be dosing patients in this disease. So, if you think about the company as a whole, 3 very unique disease states, 2 of which have the only drug of its kind and one that we believe is a true next-generation drug. And so pretty exciting little opportunity in front of us.

And if I could talk about the design for those, which is really exciting, Gena. For FA, we're going to be able to share that safety data that Bo alluded to and then also bio-distribution by endomyocardial biopsy. So, looking at frataxin expression, looking at early signs of potential disease modification and looking at echocardiography that can be quite early. Biodistribution with the minimally invasive MRI-guided delivery to the dentate nucleus is going to be instantaneous. When we perform that injection, the MRI imaging will show exactly where the drug is. So, at the time that we share that initial cohort of data, we'll be able to look at the 2 key organs that are affected, the dentate nucleus responsible for the ataxia dysarthria and bulbar function and the heart, the cardiomyopathy, we'll be able to share safety data and then we got the drug where it needed to go, which is critically important.

Yes. I think, look, I mean, look, we're like a mini Sarepta, Reata and Rocket combined with the 3 different disease states that we're in. It's a pretty unique little opportunity.

Right. Going back to FA, like any initial doctor patient feedback regarding the administration part?

Yes. Well, the feedback from the families that also goes to the KOLs that; they don't want just a treatment for the heart. They want to make sure that they treat the totality of the disease. If you lose the ability to muscle coordination, speak, swallow, what good does it do if you just solve for the heart. And so, we are getting letters from families all over the world trying to get into the trial and that I believe as long as we dose safely, that's going to lead to a long-term success of this program.

Good. I think we are on time. Maybe last quick question on the manufacturing. Part of the great data is also contribute to the high-quality manufacturing process. Maybe give us a little bit color on the scalability, the commercial supply. I think you kind of alluded to at the...

Yes, scalability is there. I mean this is a triple transfection suspension base. We're already at 1,000 liters. I just didn't sign the contracts because I didn't know the data. I waited on the data. We know what we have now. I think we have the most pure manufacturing process out there. Our empty ratio on Duchenne is in the 80s on the cardiac programs in the 90s. Those are true full capsids, and we believe it matters not only from safety, but from efficacy as well as COGS; and so we've been spending a lot of time on that as a company way before this data was released and so I think it's going to benefit all our programs. It's scalable. We just needed to make sure that we knew what we had. And so now we do.

Okay. Great. Well, thank you very much, and we look forward to the data update.

Always a pleasure. Thank you.

Thank you.