Good morning, everyone. My name is Gina Wang. I'm a Syndicate Biotech Analyst at Barclays. Welcome to the 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. Before we dive into the questions, Bo, maybe you want to give a quick high-level overview about the company.
Yeah, thank you, Gina. Thank you, Barclays, for having us. Solid Biosciences, precision genetic medicine company. Very exciting year for us in 2025. Truly almost a transformative year for us. We just released new data on our next-generation Duchenne drug called SGT-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, and we're close to filing an IND for CPVT, Catecholaminergic Polymorphic Ventricular Tachycardia. That's an arrhythmogenic fatal arrhythmia, mainly seen in children. 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 two studies in one 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. Could be the best cardiac and skeletal muscle capsid ever dosed in humans. 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. It's a very exciting little company, and that sums it up.
Okay, great. Maybe we will talk about DMD data. Recently, you presented very comprehensive and impressive data, and I think it generated a lot of excitement. Maybe walk us through, I think one part is it's also very consistent. I know it's only three patient data, but it was very consistent, high-level expression, and you did have a lot of measurements showing the consistent potential clinical benefit. Maybe tell us the next step and what's the status there in terms of 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?
Yeah, I'll tell you what, I'll start it off, and then I'm going to kick it over to Gabe 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, a 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 a P-value or change the lives of these children. 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 spectrometry, 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. Once you understand those two, 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. I'll turn it over to Dr. Brooks.
Thanks, Bo. Gina, 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 three participants, but I'll share with you and remind your listeners that in fact, we've already dosed seven participants. We've overdoubled the number of participants. 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 close to, in totality, close to the size that we know our colleagues in the field, REGENXBIO, have shared, around 20-30 participants. When is that going to happen? When is that conversation going to happen? When is that of that 10-12 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, without peer, in terms of the level of microdystrophin, the amount of positive fibers. Gina, 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 NOS in patient clinical data. I think that's really important in terms of really trying to address the biology that's abnormal with Duchenne. That's our program and 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 three pivotal trial in the rest of the world this year. That next half of the year, as Bo said, this has been a transformational 2024.
2025 builds on that with the kickoff of our registrational phase three 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. Maybe talk about the additional 10-12 patient, sorry, total 10-12 patient enrollment. You already enrolled seven as of February 17, which, like, three to five patients, I think previously you said in April. We're only one month away.
Yeah.
How's the status there?
Wonderful. You know, the boys are doing great, as we hear from, obviously, 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 is really, 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. The boys are doing really well. In terms of interest, Gina, 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, whether it's with REGENXBIO 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 it's really, they really want to look for something that can address more of their disease than what they're seeing. That was, 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 three patients, so we'll call it 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.
We really feel almost a moral need to really ramp up our dosing and be able to meet that demand.
The extra three to five patients, are you on track to complete this enrollment mid-April?
Yeah, let me just, 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, you would literally fill this trial by end of May. The demand is so intense to get into the trial. This goes way back, Gina. 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 six patients before we released any data. 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. In the process of making thousands upon thousands upon thousands of liters of material to fill the trial. We're on track, 20 patients by the end of the year, 30 patients by the end of Q1. 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. If we get the same treatment that REGENXBIO got, and we're very hopeful that we do, that's going to be the trial.
Gabriel already said, we'll have a confirmation trial up and running ex-US too.
Sounds good. Yeah, since you talk about ex-US, I think you total have six sites, five US, one ex-US, right? Canada.
That's right.
Yeah, Canada. What is the plan? I just want to make sure, right now, you don't have any waiting period. You can enroll as fast as you want, right? As long as.
Yeah, there's a small subtlety there. In our older cohort of boys, from seven to less than 12, we are just emerging from sentinel dosing. We can go parallel dosing with them very soon. In the younger cohort, up to seven, the four to seven-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 three study in the rest of the world, we actually are obliged to have a plan to study SGT-003 in age 0-18. We are engaged in doing that.
Yes, we're going to fill this phase I trial in the U.S. and Canada mostly with that kind of four to 12 year old, but we are going to be starting to dose in that younger cohort of zero to less than four as well.
Yeah, I think that's important, Gina, 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. That will be dosing zero all the way to 18 years of age.
For the, okay, so seven to 12, you're just emerging sentinel dosing. You can dose as fast as you can.
Correct.
You are not planning to dose higher than 12, right, for the pivotal study?
We will be. We will be, I think, but in terms of we're concentrating on that seven to 12. And Gina, 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 significant microdystrophin expression, we can show biomarkers, but also that we have a, that there's some signs of clinical benefit in there. We're focused on ambulation. Okay? 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. We are 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.
For the 30 patients, mainly it's four to 12, and you will not dose beyond two.
That's correct.
Outside of this age range, right?
Four to 12, four to less than 12.
Okay. Yeah.
Yeah. I want to say we are committed to those older boys.
Right. So that will be a phase three study.
Yeah, a separate cohort.
Yeah. Okay, sorry. Phase three study,
Separate cohort.
Right? The phase three study, like you mentioned, zero to 18 age. Maybe the exact age. Confirmatory phase three, what is the age?
Yeah. Again, that seven 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 therapies. We've learned a lot of lessons. We cannot repeat the same mistakes that occurred and led to the, we believe that contributed to the negative trials of CIFFREO and Embark. We just can't do it. We need to make sure that we're really thoughtful. That's exactly what we've done. We've looked at those studies. I believe that Elevidys is modestly effective. 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.
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. From that, we believe that we have a very efficient trial for a double-blind randomized placebo-controlled trial in that four to less than 12-year-old range, looking at very specific inclusion-exclusion criteria that's broad, but focused. But focused.
Right. Going back to Bo's comment, separate cohort, zero 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 three, can tell us to think about how can we look at potential benefit to the heart. We need to look at that. Gina, I wish I could sit here and tell you I had a design ready to go, but we're still looking at that data.
Yeah. Just like a rough idea, like 10 patients, 20 patients.
Oh, no.
For that separate cohort.
For the cohort.
Yeah. Like a zero to 18 patient cohort. Yeah. How many patients you are thinking? The purpose, I'm pretty sure you wanted to have a broad label potentially. How many you think that will be sufficient to serve that purpose?
We know that Elevidys got an accelerated approval for six patients' worth of pooled data. I think we want to have a data set much more robust than that. Maybe we can leave it there.
Okay. That's fair. Okay. I think we're talking about the sites, active sites. Like one part, 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, oh, for the pivotal study.
Yeah, pivotal. And then phase three will be the next step, right?
Yeah. We have such demand with the partner sites we have, and we have demand to get into the study as a center. We are expanding the center, I think the center list, but we do not really need to have a vast, much more than the six that we already have. I think we can say half a dozen potentially new sites coming on board. We need to be parsimonious because we are 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, you know what, it is closed because we have already dosed all the boys that we need.
I see. Okay. So likely existing sites?
Existing sites. A couple more.
Sites. Yeah. We talked to some doctors. They have a logistic capacity. They can only treat one to two patients per month, but those for the commercial. Here, maybe.
I don't know if that's the, 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 treat.
I think for them maybe it's because all the logistic, the insurance would take like several months. In your case, like all the sites you are active now, how big is the patient pool? Are they also treating, providing the commercial drug to the patients?
Yeah, of course. The patient pool, I mean, this goes back to my comments earlier. The patient pool is one, big, very large, not only in the US, but ex-US There are a lot of patients that want to try other therapies, including outside of gene therapy. They are lining up, and the physicians are very thoughtful about which ones to put them on. There is plenty of, I mean, like I said before, if we had all the drug right now, we could fill the trial by May. There is plenty of demand. Yeah.
Okay. Good. Next step, okay, the time, yeah. Okay. You already mentioned that. We have a few more minutes. You do have tons of other programs. Maybe talk about the CPVT, the R&D, our first half, 2025, the steps to submit, the final steps to take to submit the R&D where you are. Maybe if you can share any initial thoughts on the clinical trial design.
Yeah. Before I go to CPVT, I want to talk about FA because FA is.
Oh, sure. Of course.
DMD and FA is really a one-two punch, and you don't see many companies that have two different types of drugs like this that can really change entire patient populations and diseases like this. FA will 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 participate in this trial, and we should be dosing patients second half of the year, and then hopefully reading out those three patients in the first cohort first half of next year.
I think that that's real important because you have a one-two punch in Duchenne, meeting with the FDA later this year in Duchenne, coming out of that, reading out the 10-12 patients for the data, plus giving an update there, starting our confirmation study in ex-US, 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. We're going to be dosing patients in this disease. If you think about the company as a whole, three very unique disease states, two of which have the only drug of its kind, and one that we believe is a true next-generation drug.
Pretty exciting little opportunity in front of us.
If I could talk about the design for those, which is really exciting, Gina. For FA, we're going to be able to share that safety data that Bo alluded to, and then also biodistribution by endomyocardial biopsy. Looking at frataxin expression, looking at early signs of potential disease modification, and looking at echocardiography, that can be quite early. Biodistribution with a 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.
At the time that we share that initial cohort of data, we'll be able to look at the two 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.
Yeah. I think, look, I mean, look, we're like a mini Sarepta, Reata, and Rocket combined with the three 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?
Yeah. The feedback from the families that also goes to the KOLs is that they do not 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? We are getting letters from families all over the world trying to get into the trial. That, I believe, as long as we dose safely, is 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. I know part of the great data is also contributing 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 it at the beginning, but.
Yeah. The scalability is there. I mean, this is a triple-transfection suspension base. We're already 1,000L . 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-to-full ratio on Duchenne's in the 80s, on the cardiac programs in the 90s. Those are true full capsids. We believe it matters not only from safety, but from efficacy as well as COGS. We have been spending a lot of time on that as a company way before this data was released. 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. Now we do.
Great. Thank you very much. We look forward to the data update.
Always a pleasure. Thank you.
Thank you.
Thank you.