Welcome to the H.C. Wainwright 27th Annual Global Investment Conference. My name is Arthur He, a Senior Biotech Analyst at H.C. Wainwright. Thanks for joining us to have a conversation with Mr. Bo Cumbo, the President and CEO of Solid Biosciences. A little bit about Solid Biosciences. Solid Biosciences is a clinical-stage biopharmaceutical company focused on developing novel AAV-based gene therapies for rare neuromuscular and cardiac genetic disease. Bo, welcome.
Yeah, thank you, Arthur, and thank you, H.C. Wainwright, for the invitation.
Bo, for those who may not be as familiar with Solid Biosciences, could you start with a quick overview of your pipeline?
Yeah, so as Arthur mentioned, Solid Biosciences is a precision genetic medicine company. We focus primarily on gene therapy at the moment. Our main products are, I'll just talk about the first four, while we have many others that are in collaboration with Mayo and other groups. Our first product is for Duchenne muscular dystrophy. It's a next-generation gene therapy for Duchenne, followed by Friedreich’s ataxia. We're doing the first-ever dual route of administration to try to combat all the manifestations of FA. The third is CPVT, which is catecholaminergic polymorphic ventricular tachycardia. It's a mouthful, but it's a fatal arrhythmia that children are diagnosed with. The next product that should be in the clinic is TNNT2. It's a dilated cardiomyopathy, and it's a very severe form of cardiomyopathy. It affects about 20,000 to 27,000 patients.
Thanks, Bo. Let's look at your leading asset, the SGT-003, first. Early this year, you guys showed very encouraging data from the ongoing INSPIRE Duchenne study. Could you walk us through the clinical results you have gathered so far with these assets?
Yeah, you know, it's very important that if you haven't been paying attention, we took a little bit of a different approach on how we look at Duchenne, or at least muscular dystrophy, in our product. A lot of people were focused strictly on Western blot. We don't believe it's just Western blot. We think it's the totality of the data and how you look at, you know, obviously expression, vector genome copies. How many copies are you getting into the nucleus? Because that can give you a good idea of transduction. Fiber count, and then you head into the entire dystrophin sarcoglycan complex being put together. How many fibers can you see? A beta sark, delta sark, because these proteins really do matter. These are full-length proteins that are recruited by the scaffolding of dystrophin.
Then NNOS production, neuronal nitric oxide, combination with NNOS to CAVIN4 to beta sark, all make a big difference in the heart. For example, this dilated cardiomyopathy is a major issue in these children. We look at three different types of measures of muscle integrity: the acute phase, the chronic phase, and muscle maturation phase. All of these different biomarkers, some are more variable than others. You tie the acute and chronic together, so you can actually get a better picture. We took a very holistic look because it's just too narrow of a look if you just look at protein. You have to look at what's really going on within the body on multiple different measures, and that'll give you an idea if you have confidence to continue the trial, especially at this time where money is so valuable, you know, where you put your money in biotech.
Having a whole host of biomarkers and measurements, it really does help. That's where we're at right now. We've dosed 15 boys, all very safely. We actually have dosed more, but we just haven't disclosed the number. We're continuing to dose, you know, every single month. We've announced 15, all of them very, very safely. We've had no SAEs, no hospitalizations. We've never had to use ecomysimab, sirolimus, IVIG, at least not to date, and everything's doing very, very well. We're pleased with what we're seeing so far.
You mentioned about the safety. Unfortunately, the community has seen some setback recently with the other drug due to safety issues. So far, the SGT-003 has shown a much cleaner safety profile, particularly around the liver toxicity, right? What do you think explains that difference?
Yeah, so it's funny when we think about just anything in general. We always try to swing for the fence and find this one, you know, big differentiator. I believe that it's a bunch of little levers that can make a big impact. We talk about it all the time in the company, and I think that that's where this program really came into play. You think about our capsid first. Our capsid is called SLB-101. It's a novel capsid. It had actually never been in humans before. We manufactured it. I created it in our labs. What we do is insert RGV peptides all the way through this capsid. It's designed to look for integrin receptors in skeletal cardiac muscle. We've noticed a couple of very unique benefits because of this novel capsid. Number one, it was liver detargeting in both the mouse and the monkey.
It was only about, you know, one to two, maybe three times liver detargeting. Some people will say, well, that's not a lot. It's at least one to three times liver detargeting in two different animals. I think it's actually playing out in humans. You look at the biodistribution. The biodistribution, like in the cardiomyocytes, you can see expression 20 times greater in cardiomyocytes than AAV9. Five to ten times greater biodistribution in the diaphragm, in the quad. In the quad, in the gastroc, it's like, you know, two to four times greater. All of a sudden, you can have a lower dose. We do manufacturing. Manufacturing is very different, and we have a very high full-to-empty ratio. It's how many, you know, particles we're putting in the body that are true full. We dose everybody at a VG to KG basis.
That means if I'm dosing, or anybody's, you know, any gene therapy company, if we're dosing you out there at 1E14, and I only have a 50% full, you know, empty, you know, full-to-empty ratio, then I'm really dosing you. I'm doubling up the dose. I'm putting more pressure on your liver and the complement activation. We have a 75% to 80% full ratio in for this program. Our other programs are even higher than that. The combination of all these changes, all these little levers, decrease the viral load pretty dramatically, depending on who you're looking at. It can be up to 1.4 quadrillion different lower variants in the body. I think that makes a difference. We think that that's what's playing out in the clinic. We've not seen any of the issues yet. This is gene therapy.
We know that you could have them, but to date, we've dosed 15 boys. We've dosed more, but we've 15 boys and no hospitalizations, no drug-induced liver injury, no sirolimus, no ecomysimab, no SAEs. We feel pretty good about it. We've got to continue to dose. We're doing that, and we'll see how this plays out.
That's great. Also, for these SGT-003 trials, are you guys going to see the FDA this quarter? No, next quarter?
Yeah, that's the game plan. I think the big debate that we hold internally, and I'm having a board meeting in the next couple of weeks, we'll talk about it, is, you know, the world, this has been an interesting year. I think this has been an interesting year. We just want to make sure we put our best foot forward with the FDA, have as big a package as possible, the most robust package. I dosed six boys by, what was it, February? Seven, I think seven on February 19, because we did the announcement. I've been really, you know, I've been dosing a lot of kids lately. As I've announced, 15 patients in August, and we're continuing to dose.
We just want to make sure we put the biggest and best package in front of the FDA so they can see what we see, or at least what we believe we see. That way we can have a path. It's very important not to mess up this one shot you have with the type C meeting.
I see. At the same time, you plan to initiate a randomized study, ex-U.S.
Yeah.
What is the calculator or strategy behind that?
Yeah, we will be starting in Q4 a double-blind, placebo-controlled, multi-country, and multi-site trial. The reason is twofold. One, I want to get this drug to everybody across the globe, for all the kids that have Duchenne. There's over 250,000 kids that have Duchenne outside the U.S. We should not forget about them. Regulatory authorities are one thing, reimbursement authorities are another, ex-U.S., and really, they want a double-blind, placebo-controlled trial. They want you to hit a P-value so you can get a different rating and you can actually get reimbursed. Obviously, we've seen the challenges with other companies, ex-U.S. I want to make sure I get this drug everywhere. Number two, I think the FDA is going to really appreciate if I'm already dosing, and I think that's the key, is dosing a double-blind, placebo-controlled trial that they know they can use as a confirmation study for accelerated approval.
If they know that we're not playing around with them and they see that we're doing a double-blind trial and we're already dosing that trial, I think that's going to give them a lot of comfort. They can take a chance on efficacy. It looks like our safety profile is holding up. I think when you think about accelerated approval, the FDA can lean into thinking about a surrogate marker for clinical benefit as long as safety is there. Doubling down on both efficacy and safety is hard. It looks like I have a good, clean safety profile to date, and hopefully it holds. Then they can take a risk on the efficacy with accelerated approval, knowing they're going to have a double-blind, placebo-controlled trial already enrolling, already dosing. That's the strategy.
That makes sense. Have you guys thought about the trial design? Can you give us some of the we have over on that?
Yeah, I'll give you a little bit. I won't give you the end, but it's going to be obviously, you know, randomized. It'll be two to one. It'll be basically agent. We're going to enroll kids of anywhere from zero to less than 12, but pre-specified clinical benefit will be ages like seven, seven, eight, nine, ten years of age. A little bit older kids, those will be pre-specified. We'll look, based on criteria to get in, we'll be a little bit more lenient. We want a little bit of sicker kids so we can tease out the benefit. We'll look for a very specific endpoint. It will not be NSAA. It'll be Verizon time or Stride Velocity. Europe does use Stride Velocity as an endpoint. It'll be like one of those two.
We'll have secondary endpoints as well, focused a lot on the heart because we are seeing changes in cardiac benefit. I think that that's something to look at as a secondary or a tertiary endpoint. That gives you a little bit of flavor. We haven't decided on that. We haven't landed on the end yet. We will in the next couple of months as we're talking to the agencies.
Awesome. Appreciate it. Let's look forward, fast forward. If SGT-003 gets approved, what is this drug fitting to the current treatment landscape for the Duchenne?
I think it's great. It'd be great for the families as well as the clinicians just to have a choice. Right now they have, I mean, they're in a really tough situation as a family, right? I mean, we all know what Duchenne is. The families know it more than anybody, and they have to make really tough decisions about their child. Just to have choice, I think, is very important. Whether they want to go with one drug or another based off the education from the physician and from their own education, because they do a lot of research, I think that's going to be beneficial, especially in a disease like this where these decisions are critically important for the child.
I see. Last question on the Duchenne. When would you consider expanding into the non-ambulatory kids? I know that's a big, huge empty hole there.
Yeah.
What kind of evidence you would like to see from your current trial or in the ambulatory patient you can have give you a confidence to move into the non-ambulatory?
Yeah, it's a great question. I'm going to give a long-winded answer to say that we're going to be very cautious. We've dosed, I've announced we've dosed 15. We've dosed, we're continuing to dose. I believe we're on track to easily dose 20 by the end of the year, 30 by the end of Q1. That's our corporate goal. I'm not going to go into the non-ambulatory or the older kids until I feel I really know the safety profile in this younger population. We're dosing up to 10, 11, 12 years of age. We're getting close to this non-ambulatory group. Heavier kids, heavier, much larger fat fraction, which is, by the way, going to really change. It's a very heterogeneous population. It's going to change the profile as you dose these heavier, older kids.
You will see changes in expression, fiber count, everything else, because they're just more sicker and they have less muscle. We are going to make sure that we know what our safety profile is in at least 20 to 30 of these kids prior to even thinking about going into the older, sicker, heavier population. I'm going to work with the FDA very carefully on that because I know I have a drug right now. I know I have, as it stands today, as I'm talking to you, I know I have a safe drug. I do not want to harm that drug going into the agency with the older, heavier, sicker population. I want to get this drug to them, but I want to do it in collaboration with the FDA because I don't need any chaos right now.
Gotcha. Let's switch gears here. Back in January, you surprised the market with the R&D clearance for the 212 in FA. Could you give us an overview of the FA and how you see the market potential there?
Yeah, I view this as the best shot for all FA patients. You know, you either have cardiac manifestation or, you know, CNS and cardiac manifestation. This is the only drug of its kind that can do dual route administration. It goes direct to the cerebellum, an interdental nucleus injection using an MRI-guided pressurized catheter right to the dentate nucleus, and then IV for the heart and spinal column. The goal is, no matter where you are in the disease, if you're a 40-year-old with just cardiac manifestations, drug for you. If you're a 20-year-old with CNS and cardiac manifestations, drug for you. If you're a four-year-old that has no idea what your journey is going to be, we have a drug for you.
That is the ultimate goal, to meet the patient where they are in the course of the disease and try to hit the targeted areas that you need to. We've done a lot of work preclinically to suggest this is the best route. You know, frataxin is toxic at high levels, and if you try to push the dose up to get to the cerebellum, you're going to create a tox issue in the heart or maybe even the DRGs. This is a very elegant way to deliver right to where you want. Basically, the patient comes in, they get the interdental nucleus injection through the MRI-guided. We use gadolinium, so we're going to be able to see exactly where we're putting it. We're shooting for about 30% of the dentate nucleus to be covered.
We let the patient rest a couple of hours, and then we just do the IV dose after that. We're excited about this. I think this has the potential, if it works and it's safe, it will take the entire market because everyone will tell you it's wonderful if you can solve the heart issues in FA, but if you can't swallow, speak, move, quality of life takes over. This is the only drug of its kind that can do that.
Gotcha. I know you guys are ready to, or almost ready, getting to dosing the first patient. What's the readiness there? How's the trial design?
Two IRBs, two universities are open now. Out of three, we're shooting for three. We should be recruiting patients at the end of the year and dosing by the end of the year. Working on just changing the surgical manual. I'm working with the FDA on this as well. We should be dosing at the end of the year. Everything's on track. The FDA wants us to dose older non-ambulatory or older patients greater than 18 for the first three patients to establish safety. Then we'll go down to younger patients and start building out from there.
Gotcha. Let's look at the next asset.
Your time's up.
It's okay. I'm not going to try the CPVT as a second language speaker anyway. Maybe tell us a little bit about the mechanism for 501, how they can target treating two different mutations of patients like that.
Yeah, so we have two different types of mutations that we can target, CASK2 and RYR2. It's all about the buildup of calcium. The great news about this program is it's a signaling mechanism of action. We don't have to remodel the heart. The heart looks the same. It's just an overload of calcium in the sarcoplastic reticulum due to these mutations that cause the arrhythmias when there's an adrenaline surge in these kids. We just have to shut that signal off. You shut it off by soaking up the excess calcium. You don't even have to coat the entire heart. We believe it's somewhere right, just very similar to FA, where you know 30% of the heart is covered. You can actually shut off that signal that happens when they have this adrenaline surge and their heart starts fluttering and going into VT.
In animal models, right around that 20% to 30% excess calcium being soaked up will shut that signal right off and hopefully decrease arrhythmias. That's the goal here. We do Bruce stress treadmill test and we can look for arrhythmias. It's a pretty quick signal. Those patients wait six months or so, put them on a treadmill. It's the same. That's how they get diagnosed. They get diagnosed with the disease via this stress test. We can actually look at the efficacy of this drug the same way.
Gotcha. Okay, for the last, let's get a speed round. What's your milestone in the next 12 months? What's your cash position?
Cash position as of August is like $268 million, I believe. I'm looking at my team to make sure it's two, yeah, second half, second half of 2027. I mean, first half of 2027. We should be good there. Continue to dose patients. I want to dose 20 patients by year end. I'd like to plan out the FDA meeting, get that meeting set up. Dose 30 patients by Q1. Continue to dose patients safely. Dose FA in Q4. Dose CPVT in Q4. Then head in, you know, full steam ahead in 2026.
Awesome. Thanks, Bo. Thanks for the insight.
Thank you. Thank you.