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

So welcome, everyone, for those in the room as well as listening on the webcast. Yigal Nochomovitz, biotech analyst here at Citi. The next company that we're speaking with today at the Biopharma conference in Boston is Solid Bio. We recently launched coverage on them a few months ago. So I have senior management from Solid here, Bo Cumbo, CEO; Kevin Tan, CFO; Nicole Anderson, the Head of IR. So welcome all of you. Thank you very, very much for coming.

So let's just start with just an overview question, if we could, just introduce the company, the focus of the company, what are some of the key programs, and then we can get into detail on each of them.

Yes. Thank you, Yigal; thank you, Citi, for the invitation. Solid Biosciences is a precision genetic medicine company. We primarily focus right now on gene therapy. Three main drugs that are going to be either -- that are in the clinic, IND is open and we'll be dosing patients this year in all 3 of them, which will be Duchenne muscular dystrophy, Friedreich's ataxia, and CPVT, that's catecholaminergic polymorphic ventricular tachycardia. And then we also have another program that will be coming up next year in dilated cardiomyopathy for TNNT2. And we spend a lot of time on next-generation delivery, whether it's capsids, promoters or manufacturing process from a full to empty ratio. And that's an overview of the company. About 110 employees based here in the Boston area, and excited to be here.

Awesome. Okay. Well, obviously, it's a very topical summer for Duchenne, to say the least. But tell us about your program, or maybe just start by just explaining what's different with your vector and your construct, just to set the scene as far as differentiation versus what's available today.

Yes. We believe we have -- we have 3 different unique properties. One is the capsid itself, and we'll talk a little bit about that. Two is the construct, why it's different than others and what benefits it provides. And then third is the manufacturing platform. We believe it's one of the best platforms out there from a full-to-empty ratio. And so from a transgene itself, the construct, we're the only construct of this kind that has this unique R16, R17 domain, provides recruitment for alpha-syntrophin and ultimately nNOS. Once you have nNOS, it increases blood flow, decreases inflammation, oxidative stress. It also has effects in the heart as well, especially when you compare -- when you add nNOS to increased levels of beta-sarcoglycan as well as the domain of R16, R17 as well. And we're hoping that all of this will translate into something meaningful in the lab. So that's the first differentiation aspect of the program. Second is capsid. It's a unique capsid. It's never been in humans before until this program, which is called SLB-101. And what we've done is we've taken a parental capsid of AAV9. We've modified it. We've added RGD peptides in a certain variable region. I don't think we've ever disclosed. And it targets multiple integrin receptors on skeletal and cardiac muscle. We knew in preclinical studies that this led to one, liver detargeting. Depending on the animal species, whether it's the mouse or the monkey, there's a 1 to 2-fold differentiation in liver detargeting. In cardiomyocytes, it was 20-fold greater than AAV9. Depending on whether it's the gastroc or the quad, 2x to 4x greater than AAV9, about 5x to 10x greater in the diaphragm. All of this should provide benefit to kids with Duchenne if it translates over. It looks like it is translating over. We're using the lowest dose in Duchenne. So 1E14 with a full-to-empty ratio of 75% to 80% full-to-empty capsids in a manufacturing process. Depending on how you quantify other companies' full-to-empty ratios and the total dose, you're talking over -- it could be over a quadrillion different virions less than other companies. And we think that, that makes a difference from a safety standpoint and to be able to get to decent levels of expression, whether you're looking at mass spec or Western blot, or importantly, positive fibers, I think that, that will matter long term.

Okay. But you have shown some data already earlier in the year. So maybe you could walk through that, because there was some evidence of a very strong expression for microdystrophin as well as what looked like a good start on the safety side.

Yes. We'll start with the safety since that's been front and center. The safety side, I feel very comfortable now. We've dosed 15 boys. Well actually, we're continuing to dose kids, we announced 15. We've dosed most of the boys who are ages 5 to 10 years of age. I think we have 1 boy that's outside that age group that we've dosed. Safety-wise, looks very positive. And we basically see nausea, vomiting, very transient thrombocytopenia. Ironically, in our press release, we released 1 grade 1 liver enzyme increases. We debated on even putting that in the press release, but because of all the interesting things that are going on in gene therapy lately, we just put it in there for transparency. So safety-wise, we feel very comfortable. We've dosed 15 kids. We know pretty much what to expect now on every single patient, and they look great. We taper our steroids at day 32, I think it's important to know. We taper faster. So if you don't know Duchenne, all the kids are on steroids at a certain dose point, normally 0.75 mg per kg. That's daily, whether you're on a gene therapy or not. And then you dose up on gene therapy and then you wait a certain time period and you taper down. We taper at day 30, it's the fastest taper back down to normal baseline steroids of any company. And we think that, that matters. The fact that we're able to do that, and we've been able to do that for every child with the exception of that 1 child that has grade 1 liver enzyme increase. We've been able to -- 93% have been able to taper from day 30 to day 60, and stay off enhanced steroids. So that's great. From an expression standpoint or really from everything else, we took a very holistic approach, and we're going to continue to do that. We wanted to -- investors want confidence that your drug is doing something. We want confidence that we're to invest in a trial. And so we looked at multiple different levers. We looked at vector genome copies. Anything above 2 or 3 we feel is very positive. We were getting pretty high levels, even at 1E14 dose. Then it goes to everyone wants to talk about Western blot. Some people want to talk about mass spec. We released the data for both. But however, I feel positive fibers are very important. So how many fibers are positive in the child, depending on their muscle mass, because as you increase with age, you have less muscle, so it's important to get to at least 1 out of every 2 positive fibers or have 1 every 2 positive fibers. Then it's important, once you understand your fiber count, to look at the entire dystrophin sarcoglycan complex and quantify it. Most companies just take a snapshot, but they don't really quantify it. We try to quantify that, so we can understand the levels of beta-sarc or delta-sarcoglycan because beta-sarcoglycan is very important in the heart. And if you can get increased beta-sarcoglycan plus nNOS activity, which we show next, then we are hopeful that it can lead to a benefit in the heart. Heart and pulmonary function -- cardiac function and pulmonary function are the 2 main leading causes of death in Duchenne. So we spend a lot of time on that. Once we understood the complex was there, then we wanted to understand muscle integrity. And there's a couple of different ways you look at muscle integrity. There's the acute phase that can be highly variable, and this will be CK, lactate dehydrogenase, ALT/AST. And we can use ALT/AST as muscle markers because we don't seem to have as big of an impact on the liver as what you would anticipate in gene therapy. And because of that, we can actually look at ALT/AST since the entire skeletal muscle is breaking down in these kids. So we're looking to see if we can decline ALT/AST over time. So ALT/AST, lactate dehydrogenase, CK will your acute biomarkers. Then you can look at chronic biomarkers such as titin or troponin. Titin ties back to sort of CK. You'll only see titin released in the blood or the urine when the muscle is truly decaying. And then troponin, a lot of these young little boys, they have elevated troponin. They could be 5 years of age and have spikes of elevated troponin. They're transient in nature, but they're important to understand that it's their first signs of cardiac dysfunction at age 4 and 5. And by age 10, about half of the kids have underlying cause of cardiomyopathy. And you can see a one-way shape or form of cardiomyopathy. So we track troponin and we hope that we're decreasing their troponin levels over time, so they're having less little events in their heart. We also track ejection fraction. Kids with Duchenne, they're not normal, and they're not in this range of normal kids' ejection fraction. Some are slightly below, depending on the age, that can be right at the cusp of normal, but a little bit below. Others can have a hyper-dynamic range, because their heart is under stress, so ejection fraction is higher than normal. What we're trying to do is take both ends of the spectrum. They can get these children into that normal range of ejection fraction over a longer period of time. We believe that if you can do that if you can change troponin levels, change ejection fraction levels, just to get them into this normal range for an extended period of time. That will have future benefit for these children. So we looked at everything I just talked about to give us confidence that to invest in the clinical trial that we would hit endpoint. And we believe that we're well underway. We're shooting for 20 patients by the year-end. I think we're ahead of schedule, but you never know. Right now, we're ahead of schedule, but things could change. But right now, I'm feeling pretty good about the whole program.

Okay. So you listed a very long and detailed list of, no, that's great, of biomarkers and muscle physiology and enzymes and cardiology output. So of those, are we going to see that for all those 20 at the end of the year? Just give us a flavor for what the data set is going to look like and what we can expect?

Yes. You won't see it for 20. We've dosed 15 boys right now. After you dose them, we wait 90 days before you get a biopsy. And then after the biopsy, it takes about 6 weeks to get all the data back. My expectation is we'll go into the FDA meeting, which we're going to schedule in very short order. We should have the FDA meeting at the end of the year in Q4. After that meeting, we'll wait for the meeting minutes, that will be 30 days, then we'll release all the data. But what do we have going into the FDA meeting? We'll have about 10 to 12 patients worth of dystrophin data. And then we'll have about 15 or so -- 14, 15 patients of safety data. Obviously, we'll gather additional safety data and we can release that. But I doubt we'll have much more data than what I just -- to be able to roll out to the public.

Okay. And what -- the FDA meeting, you've talked about it in the past, but it's getting closer. So what are the goals there? What's going to happen in that meeting? And what do you want to get out of that meeting?

Yes. We're going to, one, share all our data. We feel very good about the data that's already been disclosed. I don't have any additional data, if anyone's wondering. That's why you're going to see me at this conference and maybe 1 or 2 more, and then I will be MIA. So you can feel confident I don't have any dystrophin data right now -- additional dystrophin data. And we'll disclose all that. And we'll talk about the path forward to the FDA. We're hopeful that the FDA is going to provide us a path forward for accelerated approval. We are going to be starting a registrational study at the end of the year ex U.S. So it will be a double-blind, placebo-controlled, multi-country, and multicenter trial. And we're hopeful that, that, along with the data that we present, and the data package that we're going to hopefully be able to give them next year, that they can provide us a path for accelerated approval. That will be the ultimate goal. Just give us some clarity on accelerated approval process.

Well, are there specific parameters that you're going to propose in addition to -- obviously, you mentioned the ex U.S. trial, which is an important statement to make to the FDA that that's underway or will be underway. What other sort of parameters would you hope to see in terms of what would be acceptable with the data set to submit?

Yes, we're sort of following REGENX path on that, which is 30 to 40 patients safety database, 10% mean expression for all the cohorts, and directional clinical benefit compared to natural history and using external control. That's what we're going to propose. If they request additional patients, like if they say, we don't want 40, we want 50, that's not going to be a problem. We have in the range of -- in between 20 and 30 patients in the queue of screening right now. So we've already dosed 15, we have 20-plus patients, 25 or so, wanting to get into the trial in a screening process right now, whether it's antibodies or based on criteria. And we only have 7 sites in the United States. So the number of patients trying to get into the trial is pretty dramatic. And so we're going to request 30 to 40 patients, 10% expression, directional clinical benefit. If the FDA requests additional patients, it's not going to be a problem.

And then if they give you the pathway, what's the current thinking? Like when might you be able to launch?

If they give us the pathway I just outlined, then we would file for the BLA at the end of the next year. And that would...

End of '26?

End of '26. Yes.

Okay.

Yes. Yes, because we would have plenty of patients. It depends on how much follow-up they want. If the FDA requires additional patients that have 365 days of follow-up, then that will change the dynamic. But right now, our best guess is based on the patients in the next year. But then obviously, I got to get to the FDA meeting and get some clarity.

Right. And you mentioned the ages 5 to 15, I think you said...

5 to 10.

Sorry, 5 to 10, and 1 outside of the range. What about the...

That's correct. We've dosed what we believe, and I'm not sure because I don't think anyone's really disclosed the ages, but we've dosed 1 young man under the age of 2.

Okay. So is that correct that they're all still ambulatory given the ages you said?

That is correct. All our boys are ambulatory that we've been dosing.

Okay. So to propose a label would be for the ambulatory or would it encompass everybody?

We're only going for ambulatory at the time. This is all we're going to be dosing. We're going to be dosing ages 0 through less than 12, status is ambulatory.

Okay. And then are there plans to go beyond that?

There are, but we're making sure that we really understand the safety profile. We've dosed, as we said, 15 boys that have been announced. I would like just to get up to like 30 patients and just really embrace the safety profile before we get into the older population. Because it is a riskier population. They're older, sicker, heavier. And right now, I feel pretty good about where we're sitting with the drug. And I just don't want to put it at risk.

Okay. What more can you say about the ex U.S. study? I mean one of the objectives is clear, but what else, any other details you want to convey?

We haven't announced how many patients we'll be enrolling. The endpoints will be very specific, pointed end points like stride velocity or time to rise. We will be looking at everything else, obviously. 10-meter run walk, 4-stair climb. Ejection fraction is going to play a role into this. Primary endpoints will be either -- it will be a specific either stride velocity or time to rise. Double-blind, placebo control. We will be dosing kids that are younger through ages 3 -- I mean 4, 5 and 6. However, prespecified, and that's very important, prespecified for clinical endpoints will be ages 7, 8, 9, 10, 11. Why? Because these are the kids that are a little bit more unhealthy, they're either plateauing or starting to decline on the endpoints. And that way, we can tease apart the clinical benefit over time. It will be an 18-month trial, not 12, because we believe you do need time in this type of disease, especially that late in life when there's been a lot of damage done.

And so the argument would be that you're getting the functional data through that study and it wouldn't be the expectation that the FDA would want to see functional data out of your current study because that's not how it's set up, I assume.

I mean, they're going to want to see directional clinical benefit compared to natural history as a comparator. But you can look at a couple of different -- you can break it down into different age groups, because we are dosing different age groups, they will have different benefits at different times, and we'll look at ejection fraction. I think safety, though, is also a very important discussion for steroids only. To date, our safety profile looks very clean. We see nausea, vomiting, thrombocytopenia, as I mentioned. And we have had one grade 1 liver enzyme that was transient in nature. So I feel really good right now. But I think safety will matter in the discussion.

Well, let's talk about that a little bit more since there's been a lot of discussion on this point over the last few months. Your only steroids, and as you pointed out, the taper is relatively rapid, 30 days. What are some of -- I mean, some of the other approaches that are immunosuppressive, like sirolimus and Soliris, how could those negatively impact patients if those are in a regimen versus not being in a regimen as you guys do?

Yes. I mean there's a couple of different ways you could look at it. You could look at it from the burden of prescribing it, number one. So I think you have a REMS with 1 of the drugs. I think with sirolimus, you have a REMS. So you have to have a different physician, you have a REMS, you have a lot more follow-up. But when I talk to the physicians, while they like the triple immune suppression in one sense, it gives them comfort at the beginning. However, it doesn't give them comfort if they end up with an event. What do I mean? If you're on a triple immune suppression regimen and you end up with myocarditis, what does the physician do? Because they want tools, they want to treat, they want to help the patient. And if you've used everything upfront, it makes it challenging for them. So they do think about that. The other thing is you're lowering T cells for an extended period of time, and the kids are going back to school. And so what does that look like? Commercially, it makes it also challenging from a payer standpoint. Payers already have a hard time with some of these expensive drugs. To throw 2 additional drugs in a regimen, especially Medicaid or small plans, it makes it challenging. Ex U.S., it makes it very challenging, by the way. So while we're sitting here talking about the United States, ex U.S. and certain countries, Turkey, it's got over 2,000 patients, Spain, Portugal, Italy, you can't use triple immune suppression and try to get it reimbursed. The reimbursement authorities are very challenging, to begin with. So it depends on how you want to look at it, and I think that, that will matter long term if we can continue to stay steroid-free, I mean, steroid only. And right now, after 15 patients, I can see the safety profile playing out that way.

I also want to ask you, as you talk to your physician network, your parent network, what are you hearing from the community as far as the desire and openness to additional approaches in gene therapy given everything we've seen with the currently approved one?

Yes. I think every physician that I talk to believes in gene therapy, okay? So let's start there. They actually believe in gene therapy and see the results, whether you're on a commercially available drug or you're going into trial, we hear all the antidotes. And you guys don't want to hear about the antidotes because that's exactly what they are, just antidotes. But we hear them and we hear them a lot. Even on our kids, some of the antidotes about our -- we have a boy that's doing ice skating for the first time. You typically don't ice skate if you're a Duchenne kid. These are the antidotes. So they believe in it. Now we have 7 sites in the United States. So I'll talk about those 7, how they treat, because it's different than sites that don't have a clinical trial up and running. Besides the 7 sites that we have, they come to us first. And they try to get into our trial. That's why we have like 25 or so, 25, 27 kids that are in the screening process right now. If they can't get into our trial, they try to get into REGENX trial, or even Avidity or Wave or somebody. If they can't do that, then they go on to commercial therapy. Now that's the 7 or so sites that are our clinical trial sites. Then there's about 50 other sites that are active, that are not doing clinical trials. They're taking a little bit more conservative approach, but they're still dosing commercial drug. But what they're doing from what I hear, and this is just from what I hear, is that they are thinking longer term about the follow-up that they might need, and they're just spacing out their dosing of patients a little bit more carefully, so they don't get in a bind if they have to follow up a patient more often. So I think that both of those work in our favor. It means that the patient pool will be bigger by the time we get to the market. I think also families are wanting to get into some of these different trials, and that works in our favor as well. And that's why we have so many patients that are lined up and ready to go. It's exciting, but we just got to keep doing the work.

I assume your therapy would work with the exon skippers as well.

Yes. I believe long term, and I was on a panel one time and they asked what I believe Duchenne will look like long term. I do believe it's going to be a combination therapy. And I do believe that the payers will pay for it. That's long term. And I think that they can work very well together.

Okay. Well, we could easily spend the entire time on Duchenne, but I do want to make sure we cover some of your other programs. So Friedreich's ataxia, obviously, there's been a lot of progress there with the recently approved therapy, small molecule. Yours is, of course, different. So tell us about the approach there and the types of patients that you'd be targeting?

Yes. So we plan on targeting -- all the patients go all the way down the age group. Right now, it's greater than 18 and above for our first cohort, at least for our first cohort in the first 3 to 4 patients. And the reason is that's where the FDA wanted us to go. We want to get down into the younger age groups, at least down to age 12, relatively fast, hopefully in 2026, after we dose a couple of participants very safely, hopefully. And that we should be dosing our first patient in Q4. We have 2 sites that already have IRB approvals now, and we're working on the third. It's already prescreening patients and getting them in the queue, and we should be dosing in Q4. It would be interesting to see which site is the first site, but we're excited. There'll be dual route administration, first one of its kind, where we're dosing both IV as well as direct into the dentate nucleus of the cerebellum, IDN. And we believe that that's going to be the long-term benefit of this program. When we talk to all the families, they love the fact that there are programs that are trying to help the heart. But if you can solve for or at least mitigate the issues around swallowing, speech, all the CNS mobility issues, that's going to trump the heart, and quality of life always trumps the heart when we talk to the families. We did an event a couple of months ago. We had 300 families show up. We have people all around the world trying to get into the trial. And I believe that if other companies that are in gene therapy that are focused on the heart, if they set this path for us for accelerated approval, more power to them, because it really is going to help us out because we're going CNS as well as the heart. We're trying to eventually get to the youngest kid that just gets diagnosed, that doesn't know what his or her path will be, whether they're going to end up with cardiomyopathy or severe form of FA from a neurological standpoint, we should be able to dose them. And we'll be the only program of its kind to treat all the manifestations of the disease by getting to the cerebellum, the Purkinje cells, get into the DRG and the heart, I mean the spinal column as well as the heart. And I'm excited about the program. I think it was one of a kind.

So can we get into a little bit more detail. So as you pointed out, it's 2 -- it's 1 infusion in the IV and then it's the injection directly into the cerebellum. So how is it going to work with the patient? Is it going to be all happens at once, so that you check for safety with 1 and then you do the next one? Like what are the some of the details.

Great question. It's relatively quick. The procedure is relatively quick. So first, you do the IDN. It's an MRI-guided procedure, and it's infused with gadolinium, so I can -- I won't be able to see it, but the surgeon will be able to see the coverage of the dentate nucleus in real time. And based off preclinical models, we believe if we can get to about 30% of the dentate nucleus, it's going to provide long-term benefit. That procedure takes about an hour. And at the end of the procedure, you literally have one of those small little band aids in the back of your head where you inserted the catheter. That takes about an hour. You let the patient rest about an hour, and then you start the IV, and the IV is about an hour. And so all of it happens within the same day. It's the same drug, different amounts of drug, depending on the route of administration, both very low. Because we're able to do the dual route administration, the dose is shockingly low. And we haven't disclosed the dose. We will, in short order, but it's very, very low. And it's because the dual route administration lets you get the drug right to the areas you want without having to push too much gene therapy and potentially cause a tox issue one way or the other, I think it's a very elegant way to get the drug to the tissues and hopefully change the course of the disease. So a couple of hours, total procedure, IDN first, rest, IV second, and watch the patient for a couple of days and let them go.

So when are we going to get the first look at the results?

Yes. I'm hopeful that it will be first half of '26, but we should dose our first patient this year. And then while the FDA mandates a minimum of 30 days in between dosing, which is standard for many gene therapies, it most likely would take about 45 days or so, because it doesn't always line up to get patients in, screen them, get them in the surgical procedure. So -- then we'll wait 90 days. After that third patient, we'll batch our patients and then we'll release. I don't want to release one patient, one patient, one patient. I'd like to batch at least 3. So first half, if not, right around the middle of the year.

And are these patients that could be also on the SKYCLARYS drug?

Yes, we believe that -- so we're allowing SKYCLARYS. There's not really a standard of care for FA. SKYCLARYS is starting to become that standard of care. We do allow it in our clinical trial site. But there's really no drug that treats the underlying cause of the disease. It's outside of the ones that are in clinical trials on the market for commercially speaking. There's nothing out there that's true standard of care for treating underlying cause of the disease. SKYCLARYS, so it's actively being used though, yes.

And of course, I mean, it's a first in human. So it's primarily a safety tolerability study to state the obvious. But mFARS is obviously one of the key measures. Is that something you would look at...

Absolutely.

In an exploratory way? And what would be a good outcome for that?

Well, it's too early to talk about a good outcome, especially when you're only looking at, let's call it, 30 -- I mean, 90 days post dose. But we'll be looking at mFARS. We'll be looking at ejection fraction, thickness of the heart. We'll be looking at other biological correlates, the whole picture. We'll take a very high level look at everything. And then we'll present all the data that we found and that should be middle of next year.

Okay. And then to briefly touch on some of the cardio programs. If I can say this right, catecholaminergic polymorphic ventricular tachycardia.

You said it right.

A tough one.

It's easier to say CPVT.

We'll say CPVT from now on. So what exactly is that, first of all. Just explain what the disease is and what's necessary there to have a therapeutic benefit?

Yes. Basically, it's a calcium overload. So the good news is we don't have to restructure the heart in this disease. It's really a signaling issue. And because of the mutations in the RyR2 channel, you have an excess calcium, creates an arrhythmogenic situation. And because of this, because of the way of the nature of the disease, you don't have to coat the heart and soak up all the excess calcium. You just have to break the signal. And once you break the signal, then you should be able to reduce arrhythmias over time. And that's what we've been able to prove in the mouse model. And it's the only drug of its kind. CPVT, you know these kids, you just didn't know the disease. It gets misdiagnosed a lot, epilepsy, Dravet. They end up -- a lot of kids die by misdiagnosis or they're not diagnosed at all and they're out doing an activity, whether it's basketball, rock climbing. There's a famous young man who died, but he got revived. He was rock climbing with his friends, got to the top, looked down, had a burst of adrenaline, went into arrhythmia, died, fell, he's paralyzed, he was revived. They identified that his younger brother who had died when he was like 8 or 9 had the same disease. He just got misdiagnosed. There's about 20,000 patients in the United States. It's a lot of patients. And there's no drug out there. Beta blockers, flecainide, ICD, and really nothing else. So this would be the first drug of its kind.

But that you just got the IND cleared. So it's starting now. The study is starting now -- about to start?

In Q4, we're going to -- so both FA and CPVT should be dosed in Q4. So by the end of the year, we will have 3 different clinical trials going on in 3 different disease states. And then technically, our fourth trial, which would be the registrational trial for Duchenne starts in Q4. So 4 trials.

Okay. And was there another program?

Well, TNNT2 is next. That's a dilated cardiomyopathy. That's an exciting program. No other new drug on the market for that one, no trials. And our preclinical data looks fantastic. We're excited about that one, too. So that will be our fourth drug in the clinic.

Okay. Very good. All right. We'll have to leave it there. Thank you so much, and we look forward to the updates from the meeting later in the year.

Thank you very much. I appreciate your time.

Sure.