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

Good morning, and thank you for joining Guggenheim's 2026 Emerging Outlook Biotech Summit. I am Debjit, one of the therapeutic analysts, and my privilege to welcome our next presenting company Solid Biosciences and joining from Solid is Bo Cumbo, President and CEO. Thank you so much for your time, Bo.

Yes. Thank you, Debjit, and thank you, Guggenheim for invitation.

So let's do a very quick introduction to Solid. Obviously, the company has changed dramatically since you've taken over?

The company, it's a great little company. We have about 120 employees. We market ourselves as a precision genetic medicine company. But primarily, we focus on gene therapies. Our first 3 drugs are one for Duchenne. We'll talk a lot about that today. Our second therapy is for Friedreich�s Ataxia and our third therapy is for CPVT, which is catecholaminergic polymorphic ventricular tachycardia. We have multiple other programs as well, our next program, dilated cardiomyopathies, TNNT2. And then we have an entire capsid library and platform that we build on delivery because to make gene therapy investable, again, really investable broadly speaking, we have to change delivery and delivery is focused on capsids, promoters, dual plasmids, manufacturing purity. So we spend time in all those areas as a company and hopefully lift everybody up.

Perfect. So on Monday, I believe you put out a press release aligning with the FDA on a registration study.

Yes.

How important is that in the context of everything that's happening with the FDA and any potential accelerated approval?

Yes. Look, I think that press release on Monday was a huge first step. I don't know if people realize the importance of it. This is a very unique time. I think a lot of -- I read all the press with different companies and what's going on. And so we're trying to do everything right here the best we can. We're obviously in rare disease. We have -- the INSPIRE trial is an open-label study trial, but we're seeking accelerated approval in the United States, and we're going to be asking that question of the FDA real soon. But we think from a psychological standpoint of just understanding what the FDA wants by reading all the language that other companies have received, try to do everything you can from a purest point of view, even though it's an open-label trial, and that's what we're doing. So number one, we're going to have a very large safety database. We already dosed 36 patients. We will meet with the FDA shortly. We should be over 40 patients by the time when we meet with FDA. That's going to help the discussion because currently, right now, there's no drug-induced liver injury, no myocarditis, no aHUS, TMA. I'm not saying it's not going to happen down the road, but as we sit here on the stage today, it's 0-36. We haven't looked at the data, the functional data. And I think that that's extremely important because as we talk to this FDA, we can guarantee that we've not snooped any of the data. So as you're talking to them about a stat plan or you're talking to them about natural history or external controls and how you can use it, one of the issues that they would have is how did you select this natural history? Well, we can select it with them hand-in-hand in partnership here because we don't know what the functional data looks like in our 36 patients. and we can have that discussion with them. But last but not least, going to your question, the double-blind, placebo-controlled trial. The FDA wants some kind of certainty. And I think it's very challenging in a lot of cases to do double-blind trial. But here, in Europe, Australia, Canada, you can do a double-blind placebo-controlled trial for Duchenne, and we're going to do it. And we've got the guidance from the FDA. We had a really good discussion with them. They've made some changes in how we think about the trial design and secondary endpoints. They said that the trial is reasonable, and we're moving forward. We should have actually dosed our first patient next week. But unfortunately, the little boy was really sick. And so we won't be dosing him, but we're already scheduling our next patient, should be dosing our first child in the double-blind placebo-controlled trial in the next 90 days or so, first get screened out. So we're lining up the second patient now. And I think this discussion helps with the FDA. There's clearly a lot of chaos that's going on. But if there's one drug company that you want to lean into, why wouldn't it be this one? You have a large number of patients already dosed. It's going to get bigger. We're going to be dosing 50 patients by the next, let's call it, quarter or 2. We're already at 36. It looks like a very clean safety profile. We're not using anything other than steroids. So nothing is being masked. You actually know what you got. We've started the double-blind placebo-controlled trial. We haven't looked at any functional data, so we can actually spend time with the FDA and talk about how to use things, and they know we're not snooping anything. If you're going to lean into one, this is where you lean into. So I think we're doing everything right as a company, but we're going to find out. We're going to have that meeting. Second meeting is already scheduled. Obviously, we have not held it, but it has been scheduled and let's call it the next quarter.

So ELEVIDYS has both, at least from my perspective, advanced the field and set the field back. SGT-003 has multiple discerning features, which allows you to do what you're doing with corticosteroids, et cetera. Can you sort of outline those key differences and how that plays into the planned registration study with in boys 7 to 11 years of age?

Yes. I think the great news as we were thinking about 003 many, many years ago is many of us within the company either came from Sarepta or came from Pfizer or came from other Duchenne companies. And so we really understood 3 years ago, what we thought the field was going to look like. What we -- this was before ELEVIDYS failed. It was after they failed the Phase II, but before they failed the Phase III and before, obviously, all the safety events that have plagued the drug. So we built a TPP to beat that drug, and we built it from day 1. And so what did it have to look like? And that's why we started from scratch. So it starts with the capsid, starts with delivery. You have to have a capsid that beats rh74, AAV8, AAV9 and every muscle of fiber. And so regardless of how you look at it, we call it binding capacity. It binds very quick to these integrin receptors. We have RGD peptides inserted into this capsid. It binds on integrin receptors, 2 primarily that you see upregulated in skeletal and cardiac muscle. We knew that it would transduce and express very quickly. Within 4 days in certain muscle groups like the heart, it was at 50% to 75% expression at day 4. That is dramatically different than rh74, AAV8, AAV9. You just don't see it. And then by the way, then it clears in day 4. So it's out of the blood, the capsid, and this is human subjects. In the human subjects at day 4, it's 90% cleared out of the blood, and that's going to make a difference from a safety standpoint. We knew that this capsid also got to human cardiomyocytes and expressed about 20x greater than AAV9. So that was sort of the distribution. We knew it was liver detargeting. It was liver detargeting in the mouse. It was liver detargeting in the monkey. Obviously, we can't do liver biopsies in humans, but what we can do is look at their ALT and AST and they go down. And so we're not seeing the spikes or in GGT just stays flat. And so we're not seeing what others are seeing. And so we feel confident that what we saw in the monkey, what we saw in the mouse is happening in the human subjects, at least to date with N036. Then we talked about the construct, the actual transgene itself. We know that there's other proteins that are critically important. We know that you need to have a flexible protein because you're taking a long protein, you're shrinking it down. And you want that protein to be as flexible as it can be in the human subject. And then we want nNOS created. Why is nitric oxide important? Well, it increases coronary perfusion, decreases oxidative stress and decreases fibrosis and inflammation over time. There's lots of publications out there that show the importance of nNOS in human subjects. And so we add that aspect in. We also -- other proteins, alpha-syntrophin, Cavin4 to help with the ERK phosphorylation of the heart. This construct is different than any other construct that's out there. You tie that with the capsid, you've got a really good program. But the last and not -- and should not be least is our manufacturing process. Process is really clean. You have about 75% full to empty ratio. Why does that matter? Well, these capsids don't know that they're full or empty. They're just looking for the receptors to bind. And when you actually have an empty capsid that binds to a receptor, it's basically going to give the [ Hizman ] to the full receptor. And you're not going to be able -- you're going to see in a very uniform approach in cell data that when you have a lot of falls, it decreases expression. As you increase your pools, you increase your expression in a very uniform manner. Obviously, it's going to be different than a human subject, but at least you know what to look for. But safety is a big deal. You're dosing these little boys at VG to KG standpoint. If I'm dosing you at 1E14 vg/kg and I have a 50% full ratio, I'm literally having to double the dose to give you the true falls. That's going to put pressure on the complement system. It's going to put pressure on the liver. These are the things you want to avoid if you're going to build the next-generation program. We took all this into consideration. We came from Duchenne companies. We know what we're trying to beat. If you're going to innovate -- if you're going to cure a disease, you need to continue to innovate. You can't have one company dominate the landscape. You have to have multiple companies, whether it's Avidity, Wave, Dine, us, et cetera, building next-gen programs. I hope the FDA realizes this. This is -- I came from back in the day in mid-'90s of HIV. I know I look young and sprite, but I was -- I started in 1995. And it's pretty amazing. By the way, I'm clearly not going to let you get to the second question. But it's pretty amazing when we think about how important innovation is in this industry and how if you really want to cure a drug -- a disease state, you have to have multiple companies trying to innovate. And I think that that's what the FDA is going to see here, and I'm very hopeful. The funny thing is I'm just going to keep going. The funny thing is we sit here and we talk about the reasons why I believe this program is the best program out there. We'll talk about nNOS, you'll talk about the capsid. We'll talk about everything I just mentioned. Ironically, what's going to end up taking this market is ease of use. Ease of use is so simple. And so you think about physicians, why are physicians only dosing 40 patients, roughly 1/4 of ELEVIDYS. It's not because the drug doesn't work. It's because it's challenging to dose. You have to monitor it. The biggest thing for these physicians is their time. It's not about anything else. They're treating SMA, CPVT, I mean, Charcot-Marie-Tooth, limb-girdle, FSHD, all these diseases, then you get to Duchenne. What do you end up with? You end up with 40% liver injury, somewhere between 10% and 15% hospitalizations. Cardiomyopathies that you're seeing, then you're having to use sirolimus or eculizumab. Different physician has to dose sirolimus. Different physician has to dose eculizumab. You have to monitor levels for the kidney. You can get gut necrosis in the little children. All of this takes time. And then when you start pulling sirolimus off, what do you do? You have to make sure you monitor because you don't know what's up underneath the waves. Ease of use is going to end up taking this entire market. I can sit up here and talk about why my drug is going to be the best drug out there from a scientific standpoint. Physicians' time is going to end up being the major role in market share.

All right. There was probably an interesting learning for you guys during your clinical trial process in terms of infusion rates, especially given the binding and the very rapid uptake. Anything you could share from that and how that's to get?

Yes. It really was about how we use steroids. We filed some method of use patents. And so we dosed our first 10 boys. We noticed some variability in the children. Most companies would say, "oh, it's variability" due to heterogeneity disease. We didn't believe that. So we looked for any markers. Is it weight? Is it age? Why do you have variability? We did find a marker and that marker -- and we'll talk about that marker at the MDA conference. But realistically, it all came down to the first couple of days and how you dose and how your body reacts to the AAV and how it gets -- how important that first 24 to 48 hours is for the drug to get into the nucleus and then transcribe and ultimately express. And we noticed that there is a signal that certain children had and that decreased expression. And we're trying to solve it with how we dose with steroids. We were dosing this program, and we were using increased steroids on day 1 of dosing. So if I dose you today with 003, I'm also increasing your steroids on the same day. And we found that there is a signal that if we move the steroids back 3 days and just bring the steroids back, so you start your increased steroids day minus 3, all the signals change. And we think it goes back to how unique this capsid is. We see it in the animal studies that it's -- we're seeing transduction and we were seeing expression at day 2 in mice. And so we know something is going on with this capsid that's very unique compared to all the other capsids. You're seeing massive -- massively increased time to transduction and expression. And so we have to think differently. We can't just treat this like a typical AAV. So we just moved the steroids back. And we believe it's going to change everything. And that's why we filed method of use patents on how you use steroids. Because if you look at what the world is doing right now, we have 50-plus academic labs and partnerships with small companies already in place. My guess is it's going to be 100 in another year. And why? Because the physicians and the researchers are voting with their feet. They're going to move away from first-gen therapies. In 3 years, you're not going to see new programs come out with rh74 or AAV8. And why? Because there's better delivery. And SLB101 is going to end up being the workhorse for gene therapy period. You can see it how those physicians are moving. So this is where the world is going. We wanted to follow those method of use patents because I think on how you use steroids with this SLB101 because I believe, and this is just my belief, is that it's going to change whatever disease state they're in. So we have a company that we know we're working with that they're in FSHD. I fundamentally believe how you dose these steroids with SLB101 in that program for FSHD is going to change their course. So I -- that's why we filed the patents because we believe we have a tiger by the tail here with 101 and with our 003 program.

With respect to your registration study, do you think 18 months is the right time point to do the final assessment?

Well, personally, I would have gone 24 months. I couldn't convince physicians and families to go out 24 months. You're dealing with the disease state that's been ravaging the body for extended period of time since the wound. By age 12, that's typically when people -- the children lose ambulation. The fat fraction is 80%. That means 80% of the body is fat. So like when you're at like age 7, 8, 9, 10, you're 40%, 50%, 60% fat fraction depending on the age. I would have preferred to go 12 months, but you can't convince families to do a double-blind placebo-controlled trial in a kid that's ultimately going to unfortunately pass away due to the disease for 2 years. 18 months is a really good start. You will see change. I think we made a lot of mistakes in our early trials. We used ages 4, 5 and 6 kids. While they're not normal, but they are increasing in development over time. You use a clinical endpoint as NSAA, a very blunt instrument that's subjective in nature. The physicians only got 0, 1, 2, 3. You get into the trial, rise time was less than 5 seconds. So you only selected the healthiest 4-, 5- and 6-year olds for the trial. And then you didn't even give the body time to adjust and your trial is over 52 weeks, adjust to the new protein. We've solved for all this. We're using ages for Phase III double-blind trials, 7, 8, 9, 10, 11 years of age. Why? Because they're either plateauing or declining. We're using time to rise as a very specific endpoint and the FDA agreed to the time to rise as the endpoint. We're -- to get into the trial, it's going to be higher than 5 seconds and lower than 10 seconds. It's right in that sort of sweet spot where the kids are either plateauing or slightly declining. And then we're going out 18 months. We're going to let the body adjust to the new protein for 6 months, and then we'll have 12 months of time for us to see benefit. I think from a probability of success to hit the endpoint, this trial has all the aspects of it. And then I personally believe it's got the best drug and right now, it seems pretty clean as well.

Let's pause on DMD for a second and then talk about the FA program. You've sort of taken a very different approach to it, dual vector targeting 2 different things. Can you just walk us through the strategy there?

I would tell you, I should be more excited about Duchenne than I am FA, but truthfully, my heart is in FA. I think this is going to be an AveXis-like moment in FA. That's my personal belief. We're going to have to wait and see how things play out. We believe, fundamentally, you got to get to the dentate nucleus of the cerebellum. Of course, the spinal column is important and the heart is important. And all 3 of those areas become difference of importance or different weight of importance as you age, as you mature because the disease continues to ravage the body. We're the only company that's doing what we're doing, dual route of administration. So we start with an MRI-guided enhanced imaging into the dentate nucleus. It's a stereotactic MRI guided. You should -- Dr. Lonser, out of the Ohio State University, he's our neurosurgeon, and he is ecstatic about what we tried to do and what we're able to accomplish. You start with the neurosurgery. You hit both sides of the dentate nucleus. We wanted to cover 15%. We believe that, that was going to be meaningful for these patients as you think about diffusing in the dentate nucleus. We blew that out of the water. The -- you want to talk about precision genetic medicine and we were trying for the center of the dentate nucleus, we're 0.3 millimeters off of the center of the dentate nucleus. That's how guided it was. So you're not going to have capsid going all over the brain. Anyone who's going to try with a neurotropic capsid or try to push the dose up to get to the dentate nucleus, you're just going to have capsid going everywhere or you're going to cause a tox. Because we can do this and we're at the E9 doses -- dose in the brain, and that's total VG. We can actually then lower the dose for the spinal column in heart. It takes about 2 hours or so for the neurosurgery. We let the patient rest an hour, then we dose IV. IV can be a lower dose as well, E12, gets to the heart, gets to the spinal column. And I think about this when we thought about programs and how we develop a program, I thought about what would I do if I'm a father of a little girl with FA that's 5 or 6. Am I going to wait 15 years to understand if they're going to have dilated cardiomyopathy before I dose? Or am I going to try to help this -- my child right now? And the answer is I'm going to do everything I can to help the child right where the heart of the matter, and that's getting to the dentate nucleus and then protecting the heart and the spinal column over time. There's only one company, one drug that's going to do that. That's this. We've dosed our first patient who was 27 years old. He was very, very sick. And FARS capsid 93. He is in the high 80s. If we see any signal from this guy, it's a miracle. And I will be screaming from the rooftops. I'll tell you, I'm personally very excited. We're about I don't know what the data is right now, but I think we're about 40 days out from dosing. It's doing great. He had a headache, resolve with Tylenol, and we haven't seen anything else. And we're already hearing things, but we don't have proof yet that the gentleman is doing very, very well from an efficacy standpoint, we have to wait. I think this could be one of these AveXis type moments. Obviously, SMA is so different than FA from a mortality standpoint, but I think this is one of these that can change the disease state overnight. We already have 50 patients trying to get into the trial at Ohio State. That's one site, 50 patients. If we see benefits in this drug, if we see safety, the entire world is going to flock to this program if you have FA.

And when do you expect to put out data on this one? Do you have a preset number of patients you want to treat before you...

Yes. We're going to dose 3, 6 patients over the course of the year, 3 patients, and then I'll probably read out second half of the year on the first 3, but we'll continue to dose Cohort 2, we call it Cohort 2. So we'll dose Cohort 1, Cohort 2, but Cohort 1 will probably read out second half of the year. And if it's anything great. I think this is a very unique little company.

Last few seconds. What do you think should be the right bar for mFARS here because current standard of care, the bar is...

2.14.

Exactly. So...

Yes, it's 2.14. And that's the regulatory approval for SKYCLARYS. So it's 2.1.

Well, awesome. Looking forward to all the data updates this year and especially on the regulatory side. Thank you for making time Bo.

Thank you, Debjit. Appreciate it. Thank you very much.