Hi, guys. Good afternoon. I'm Ellie Merle, one of the biotech analysts here at Barclays. Joining me from Barclays is my colleague, Tejas Wein. We're very happy to have Solid Biosciences here with us today. A lot to talk about after a data update yesterday. Joining us from Solid is Bo Cumbo, President and Chief Executive Officer, and Gabriel Brooks, Chief Medical Officer. Thank you both so much for making the time. Maybe to begin, can you give an overview of your program, and sort of where you see it in the DMD landscape?
Yeah. First, thank you very much for the invitation. Thank you, Ellie. Yeah, Solid is a precision genetic medicine company. We focus on our lead programs, Duchenne muscular dystrophy, called SGT-003, followed by Friedreich's ataxia program. We also have multiple cardiac programs, CPVT, TNNT2. We make a host of delivery technologies such as capsids, promoters, the dual plasmids, for gene therapy delivery as well. Do you wanna go in the DMD program?
Yeah. Yeah, let's go for it. I mean, there's a bunch of DMD gene therapy programs, so, let's talk through your program and how you think it compares to the others?
Yeah, you know, obviously they're not head-to-head comparison trials going on, but I think, 003 is really one of the most comprehensive datasets that's out there. We take a very different look than most companies. We not only look at transduction and expression, but then we take the next step and really focus in on muscle integrity, satellite pool preservation, cardiac ejection fraction, troponin, increases or decreases. I think overall, what we're so proud of is that we have generated a pretty large dataset and growing, pretty rapidly and, you know, that's what I think we're most proud about right now.
Great. Well, let's talk about the data update from yesterday. Yeah, what was new from the data?
Yeah, I'll tell you what, I'll start, and then I'll kick it over to Dr. Brooks, who's our Chief Medical Officer. I think, you know, what I'll just say is, we're through 20 patients right now, and we have 40 patients dosed, I'll say 20 patients that we have expression data on. I think what I'm most proud of is that it's very stable. There's not a lot of fluctuations. Everything looks very comprehensive. Everything points in the same direction. It's the lowest dose, it's the highest expression, and it's the easiest regimen. From a commercial person, that's gonna resonate in the market. I'll turn it over to Dr. Brooks to go over the data and the clinical data, etc.
Great. Thanks. Thanks, Bo. You know, Ellie, right now, the data that we've been showing is our Phase I/II INSPIRE DUCHENNE study of SGT-003 in boys that are ambulatory, where, as Bo's alluded, we're really grateful to have 40 young participants in this trial. Then we have the IMPACT DUCHENNE study, our double-blind randomized placebo-controlled trial that's already enrolling in the rest of the world. What we showed in Orlando just yesterday was that, you know, we have, as Bo alluded, really outstanding expression, 60% mean normal microdystrophin and 63% of the fibers, as well as really compelling downstream markers that show muscle protection by CK.
All of the markers that we look at are coming down nicely, which is really important to show that this microdystrophin is being effective in protecting muscle and preserving muscle. We uniquely are looking at the need for muscle to regenerate, and what we're seeing is that need come down with after the drug has been administered. You know, Solid Biosciences was founded by a family that was touched by Duchenne muscular dystrophy, and so we've been really careful to listen to the needs of the patients and the families, and one thing we hear about is we need safer drugs. You know, we designed this drug to avoid the liver, and that's what we're seeing. We're seeing actually AST, ALT coming down 'cause that's released from the muscle.
You know, in that week nine period where we know, the experience with the currently approved drug is that there can be a lot of incidents of liver toxicity leading, in fact, to hospitalization and unfortunately some fatalities. We don't see any increase in the liver biomarkers at that time period, and that's really important. Another piece that's important to families is, as Bo alluded, how easy is it to tolerate this drug? Meaning, do you have to have long, high-dose steroids for a long period of time, which can lead to weight gain, can lead to behavioral problems. The families can really have a hard time when you need to have long, high-dose corticosteroids for the 60+ days of other products. We've actually reduced the time of high-dose steroids to only 30 days and then taper those down to their normal regimen.
We've been effective at doing that without seeing any of these liver abnormalities. That's really important, I think, for the families. It's important for the boys. We've been able to do this to conduct this study with this drug with steroids alone, meaning that those families aren't having to worry about, "Is my kid gonna get sick because they're on high doses of much stronger immunomodulatory regimens like eculizumab, sirolimus," where these boys could unfortunately get sick from an opportunistic infection. Here, we've been grateful to see that all of this hard work we've been doing to try to make a safer product seems to be showing in the clinical trial to do just that.
Great. Yeah. I guess, very impressive data set so far, but one thing that might be unique is you guys have kind of held back some of the functional data.
Yeah.
Maybe could you talk us through that decision and your overall, like, data disclosure strategy?
Yeah. We've actually stated this I thought very clearly. I saw some people on Twitter saying, "Where's the data?" We've, you know, consistently said what we're about to say today. You know, a lot of the issues that companies that have an open label trial get into is they look at the data, and then they find a natural history database, and they do the comparison. They do so after they've looked at the data, and the FDA, you know, sort of frowns upon that because they think that they're, you know, snooping the data a little bit and picking the natural history compared to the dataset they have. We've made it pretty clear that we want to align with the FDA prior to analyzing any functional data.
We give you all the updated safety database, which is in a 40. We provided that yesterday, all the dystrophin data, all the muscle integrity data, the cardiac data, et cetera. We have held off on the functional data, on analyzing the functional data. It's actually in the third party. The FDA, if they wanted to come audit us to see if we've ever looked at the data, they could see that we haven't. That way, when we're having a conversation with them on how to look at natural history literature and create a comparison so we can go forward for accelerated approval, they can feel very comfortable that we're being upfront and honest about that, you know, what we have, what we don't have, and we can select natural history together.
We're gonna meet with the FDA in this quarter, and that's only a couple more weeks away before it ends. We're gonna meet with the FDA, start having that conversation with them. I think it's gonna take one-two meetings, hopefully to align on path forward for accelerated approval, how we can use natural history, how we can analyze our data to the SAP that's already been submitted by Dr. Brooks. We'll analyze the data, and then we'll share it with the world. I think it's a very thoughtful plan, whether whoever's in the FDA, you know, I think they'd appreciate how we're being very thoughtful about the data.
If I could, Bo, one other piece there is, you know, as hopefully is conveyed, we have been really rigorous about how we've looked at all of the data, whether that be biomarker data or functional data. Here, we're preserving the integrity of the time function test data, and we're also doing other measurements of function of these boys, including the Duchenne Video Assessment. What is that? That's a way for the family to capture activities that these boys do at home. It's analyzed by a third party. What they're looking for isn't speed. They're not saying, "Is he getting up a couple stairs faster? Is he getting up from the floor faster?" It's how he's getting up from the floor, how he's walking up the stairs, what kind of compensations he's using.
Why is that important? Well, number one, These boys don't live in the clinic. They live at home. really, how are they functioning at home is the most important thing to that boy in their life. we're assessing these. A third party is scoring them. the beautiful thing is we actually get the opportunity to look at these videos, and what we're seeing is really remarkable in these boys cutting out to a year where you see that they're doing these activities like getting into a car or walking up the stairs, and what we're noticing are less compensations. That's really exciting for us.
The videos were presented at the MDA conference this week.
Yeah. Maybe to talk about your phase III design, which again, rather uniquely, you're running a placebo-controlled, and you recently announced FDA alignment on that design. Could you walk us through that conversation and how you arrived on the endpoints and maybe the overall plan for that trial?
Yeah. I'll start it off, and I'll kick it over to Gabriel. Realistically, it's extremely important to run a double-blind placebo-controlled trial for two reasons. The first and foremost is we know that we have a drug. We absolutely want to get this drug to every child that has Duchenne, not just in the United States, but the rest of the world. If you look at how the HTA assessments for reimbursement work ex-US, we have to hit a P value, and we have to you know hit a P value and do a rigorous trial. Excuse me.
We're very focused on making sure that we get this drug to all the little boys, and that's one of the reasons we're gonna use this double-blind placebo-controlled trial for registrational purposes, ex-US, hit the p-value hopefully, and then get reimbursement. However, we can also use this trial for confirmation study with the United States with the FDA. They're gonna feel very comfortable that when we go forward and ask for accelerated approval based off the dataset that we have for INSPIRE, that they know that they are gonna get the, you know, confirmation study from the double-blind placebo-controlled. I think that's gonna give them a lot of confidence as Dr. Brooks and others are speaking to the FDA. It's the right thing to do, and that's where we're at.
Now I'll turn it over to Dr. Brooks to talk about the trial design.
Yep. Yeah. Thanks, Bo. To your question of, how did we find alignment with the FDA? We approached this from the perspective of rigor. We wanted to make sure that drug development 101, we're picking the right patient population, we're picking the right time point, and we're picking the right follow-up time. We are in a perfect position because there have been folks that have gone before us. The EMBARK study, the CIFFREO study. Though they were both negative studies, we had the opportunity to learn from them, and we did.
We learned what patient population to select, and this is what we spoke with the agency about, that we wanted to take those patients that are more in the predictably declining phase, which means that it's a more homogeneous patient population, which is much easier to see a signal. Drug development one-on-one. Also, we need to have a more calibrated sensitive marker of function, and certainly the NSAA is a great epidemiologic tool. It's not great for drug development. We're using time to rise, which is more sensitive and more calibrated. Finally, we know, and can tell us this, that if you just wait one year in these boys, you know, they decline, but their decline is gradual.
Being able to say, "Are you stabilizing?" You know, we hope to say, and I really believe this, that we might actually see improvement, but at least if we see stabilization, one year can be very tricky to see that stabilization. You need to go a little longer. We went 18 months. For those kind of three pillars of, you know, drug development, you know, we had a really great advantage of having these studies go before us. When we came to the FDA and we submitted our study design, the alignment was pretty rapid.
I think it's important for the FDA to know that we're doing this trial prior to us coming in for the second meeting and talking about accelerated approval. They know we're not taking shortcuts. You know, we're gonna give them the trial that they want. You know, hopefully, as we go speak to them in the next couple of weeks, it gives them a lot of confidence that we're doing the right thing.
Yeah. I think one other thing you guys have made cardiac as kind of a centerpiece of your data set as well. Could you maybe talk us through why that's so important in Duchenne's and what you could show there?
I'll start and kick it over to the cardiologist on the stage. You know, I think it's I've been in Duchenne for a very long time, and I think it's extremely important when you think about cardiac disease to understand that, you know, these little boys are, you know, unfortunately, they're gonna die from cardiac and respiratory disorders. It's interesting, though, when you think about it because there's two camps. There's the camp that really understands what we're trying to do, and there's the other camp that says, "You don't have cardiomyopathy or low ejection fraction at such an early age." And for the most part, they are correct. Others, there's a lot of heterogeneity in the disease. You do see lower than normal ejection fraction. Every one of these boys, every couple of months, will have a spike in troponin. They leak troponin constantly.
I find it very interesting when, you know, the families of these little boys, you know, go to see their doctor somewhere, you know, 10, 11, 12, and are shocked that their son gets told or the, you know, the physician tells them, "You have ejection fraction in the 50s, and your son has cardiomyopathy." They're just blown away. Realistically, it didn't happen overnight. It happens actually on, you know, unfortunately over four, five, six years, starting at age four or five, just micro tears, troponin spikes, ejection fraction drift, and then all of a sudden you end up with the diagnosis. We spend a lot of time on this because we know you really have to get to it early. You really need to start thinking about this at four, five, six , seven years of age.
Hopefully you can extend, you know, the child's life long term by increasing ejection fraction high and keeping troponin down. I'll turn it over to Dr. Brooks to talk about our results. I think it's critically important that we do this.
Yeah. Just to follow on the background there that Bo gave so well, you know, these families, this is a diagnosis they dread. You know, they're already dealing with so much and coming into these appointments with their neurologist, and when they get the news that now the cardiomyopathy has started, I mean, this is something that is inexorable. It's gonna just be a progressive decline. Our drug has unique properties in terms of the nNOS binding domain that make it, you know, a prospect for actually addressing the cardiomyopathy. Well, that's great. On the other hand, we know that this capsid, POLARIS-101, targets cardiomyocytes 21 times higher than AAV9, already a potent AAV for cardiac targeting. When we looked at the INSPIRE phase I/II study, we really looked at the cardiomyopathy from the standpoint of safety. Why?
We're potently targeting the heart. Could there be the potential of cardiac injury with this capsid? That's what we looked at. As Bo is alluding to, in fact, instead of seeing safety signals, we have never seen myocarditis. We haven't seen declines in cardiac function. Very, I think, an exciting news is what we see instead is in those boys that have an EF that is on the lower side, we're actually seeing an improvement of ejection fraction, the way that the heart is pumping, the amount of blood that it pumps actually looks like it's coming into the normal range if they started and they were abnormally low. As Bo's alluding to, a marker of myocardial injury called cardiac troponin seems to be coming down.
We know these boys, they don't have rip-roaring troponins that myself as a cardiologist would necessarily care about if I was seeing somebody in the emergency room. But the fact is that they have slow, smoldering cardiomyopathy. Every single boy, until it becomes evident. You know, that's when the family knows they're in trouble. Here, what we are seeing is we're putting out that fire. It seems to be that we're putting out that fire with the troponin coming down, and very excitingly in those boys that have manifestly lower function of their heart, it actually seems to be improving after therapy. These are early days. This is really motivating us to focus on the potential cardiac efficacy signal.
We want to change and pivot to say, instead of just looking at safety, we'll continue to do that, but now we have the opportunity to look at efficacy.
Maybe just in the last few minutes, could you just remind us kind of the cadence of the regulatory strategy, maybe as a base case over this year, and maybe just with how things are evolving in the landscape that could potentially change?
I mean, you know, we laid it out earlier this year that we wanted to have at least three meetings. The first one was going to be talked about the double blind placebo control, get that out of the way. That's done. The second meeting is coming up this quarter, obviously in the next couple of weeks. We have not held the meeting as of today. We have submitted the briefing book. We'll talk there about a pathway forward for accelerated approval. Is there a high unmet need? Is there a path for us? Talk about how we can use our data and, you know, analyze our data.
I think third meeting then, if we can align somewhat on the first three objectives in this meeting, the third meeting would be to talk about okay, how much data do you want? That way we can generate it. We've dosed 40 patients. Dr. Brooks is continuing to dose additional patients. We're going to have a tsunami of data coming in over the next couple quarters. How much data do they really want? We'll align there. We have some CMC meetings we're working on. We've already had a CMC meeting that we squared away the potency assay. Now we'll start working on the PPQs, and we'll do that as well.
If everything goes as planned, then hopefully by the end of the year, we can get alignment on a pre-BLA meeting and then actually start filing either very late this year or early next year, as a rolling submission. That's if everything goes to plan. You know, we're taking a pretty conservative approach, but we're moving really fast actually from not only the amount of data that Dr. Brooks is generating on the INSPIRE trial, but already starting our double blind placebo-controlled trial as well. You know, we'll see. Do you have anything else to add?
No.
Maybe just in terms of your plans for commercialization and your latest cash runway, how you're thinking about the strategy?
Yeah. Cash runway, we were very fortunate. We just raised $240 million. Puts us cash in the first half of 2028. We have a significant runway and we can just focus on doing the job. Commercialization, I plan on commercializing this myself, both US and ex-US and definitely in select countries, ex-US. In US, we've done this many times and looking forward to competing against whether it's Sarepta or REGENXBIO and seeing what this. I think this drug is, you know, from a commercial standpoint, best in class. Why? It's the lowest dose, it's the easiest to use, but it's the highest expression. It's pretty simple.
It's outpatient, couple, you know, couple hours in the clinic, kid goes home, and ease of use is gonna really help this market.
What's the latest with your interactions with the ex-US regulators?
We speak with them and we also have ILAP designation in the UK, which is really setting us up for potentially first in class there. We're working on hiring a head of commercialization ex-US as well to start working on all of the HTA assessments and a head of regulatory ex-US. We're going to spend a lot of time in select countries, the larger countries, in EU, and we're going to commercialize there hopefully in the next couple of years.
Great. Well, thank you both for joining us and,
Yeah. Thank you
Sharing all the updates. Appreciate the time.
Yeah. Thank you. Thank you.
Thank you.