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Welcome everyone to the Piper Sandler Healthcare Conference. My name's Biren Amin. I'd like to welcome our next company, Solid Biosciences. With us, we have their President and CEO, Bo Cumbo. Welcome, Bo.
Yeah. Thanks, Biren. Thank you.
Maybe just start off high level. You know, companies clearly focus on the gene therapy area. Can you talk about, you know, the focus in terms of the pipeline, and how you're, you know, differentiating to some of the earlier generations of gene therapy that have been developed?
Yeah. I think, I think, you know, Solid Biosciences is a really unique little company. We are a precision inject medicine company focused on primarily gene therapy. Main, main disease states are Duchenne muscular dystrophy, Friedreich's ataxia, CPVT, and TNNT2. And then we have a host of other cardiac gene therapies. We do build our own platform. We believe that, we believe that basically gene therapy, if we want Gen2, Gen3, and that's where we have to get to, it's all about delivery. We make our own capsids. We make our own promoters. We make dual plasmids to better purity on manufacturing. We spend a lot of time on that so we can create better next-gen programs.
'Cause gene therapy as a modality, we just need to get away from the first-gen delivery tools, whether it's capsids like rh74, AAV9, AAV8, etc., and then move on to better promoters as well as, try to increase your purity by using dual plasmids and other, techniques. Very exciting little company. We have a lot going on right now.
The lead is SGT-003.
That's correct.
The gene therapy for DMD.
That's correct.
You know, clearly there's been a lot of interest around the space over the last year. Can you tell us how, you know, this program differentiates? You have also, I think, presented some early data from the phase I trial. Maybe, you know, share some of the insights from that trial and how this essentially differentiates to Sarepta's ELEVIDYS.
Yeah. You know, we did something that not a lot of companies do. We've scrapped our old program and took a holistic look at what we need to do to create a true next-generation gene therapy for Duchenne. We rebuilt it from ground up. We changed the manufacturing platform, and we changed the capsid. So this SLB101, this is a novel capsid that's never been in man before. We use these RGD peptides that focus in on two types of integrin receptors for skeletal and cardiac muscle. Really everything that we saw in the mouse and human cardiomyocytes looks like it's translating over to humans. That's very exciting. The construct, we have the only construct of this kind where you have this repeat domain R16, R17.
When you have that domain, you can actually recruit for other proteins. One of them's called nNOS. nNOS is really required in human life to increase blood flow, decrease fibrosis, inflammation. We think that that's gonna make a huge difference in these kids with Duchenne. We also can recruit for some other proteins that we're investigating now, looking at how this could impact the heart, such as cavin-4. Because we saw early signals of cardiac changes, we were looking at it for safety. Yet we're noticing all our little boys that are either low ejection fraction or low normal ejection fraction, they're increasing their cardiac output. We didn't really understand exactly why at first.
Now we're understanding some of the other proteins that we can recruit for, such as cavin-4 that helps with the ERK phosphorylation in the heart. Then combined with nNOS and high levels of beta-sarcoglycan and delta-sarcoglycan that we're able to, you know, reproduce, we think that this is gonna have a huge impact on these kids. We've dosed a decent amount. We're very excited about the program to date. We, you know, we are highly focused on safety, especially in this space right now. I think our last update was 23 patients. I think I said that we would hit 28-30 by year end. Ironically, we're not gonna be dosing after this week, you know, just because of the holidays and kids. You want to make sure you have the right docs.
I'll hit that number. You know, I've got a real good line of sight. Unless something crazy happens, I'll hit that 28-30 this week.
On the 30 patients, I think the company disclosed that you plan to have sessions with FDA in the first half of 2026. How much data will you share from the 30 patients? You know, I guess you'll have to share all the safety data, but how about from an efficacy valuable standpoint?
Yeah. We have the data. We just haven't analyzed it. The reason we have is we wanna make sure we have the conversation with the FDA around the stat plan and using external control. Let's take one step back. We had planned on a meeting in Q4. That meeting in Q4 was really gonna be a hodgepodge of items. There was gonna be a lot of discussion. We only had one hour with the FDA. We chose to break that meeting up, that one meeting into three meetings. Excuse me. We're gonna start having those meetings early Q1. The first one we'll be talking about the double-blind placebo control trial that we have going on in the ex-U.S. countries.
We think that that's gonna be very important for the FDA because if we're going for, you know, there's guidance out there. The FDA put out guidance in December 2024, looking at accelerated approval. They said basically you can have accelerated approval as long as you're starting to dose your registrational trial. We'll be dosing our registrational trial very, very soon. By the time I have that meeting with the FDA to talk about external control, they'll know that we're already dosing that trial. I think that's gonna help the conversation. To your point on data, we wanna actually talk to the FDA. We wanna go over the stat plan. We wanna go over how we're gonna use external control. That way we don't snoop the data.
You know, by showing everyone all the data ahead of time, the FDA might say, you know, you've already taken a look at all the data. We haven't done that. Ex-expression is one thing. Clinical endpoints are another. You know, we're just holding off on the clinical endpoints. But, you know, we have all the data.
Once you have buy-in from FDA on external control.
Yeah.
You will analyze the data or.
Yeah.
Would you hope that you would need more patients?
You know, the great news is we're gonna have more patients. I mean, you might have to help me with quick math here. I have dosed 23. And I have 72, total in the queue. That's like 49. I have 49 patients that are, are that could be even bad math, but figure it out. That's 49 patients that are in the queue. If the FDA literally says, "Hey, dose 30 more patients," that's like two months. It's, it's we're dosing really, really fast.
In terms of external control, what, what's a good reference for an external control? Could it be Sarepta's randomized study, for example, the control arm there?
Yeah.
Could you use that potentially?
It's funny. I brought that up to McCary and Prasad one time because they actually hold all the best external control data in these placebo arms. I wish the FDA would allow companies like us and all the other companies to use that data. I think the answer is no on that. I think we'd have to use external controls from C-TAP and other organizations that have good data, but they're not the double-blind placebo control type data. I wish they would. If the FDA would allow that, it would really help all rare disease companies.
On that C-TAP data, would you have to age match too?
Yeah. Yeah. You'd have to be.
Like the four to seven-year-olds that you're.
Yeah.
Currently enrolled?
Yeah. That is why you talk to the FDA first before you do all the analysis. You say, "Okay. Here is our plan. Here is, you know, here is how we are, we are age matching. Here is how we are gonna do the control." You get that agreement, then you do the analysis. As long as you have not done that, and we have not done that, then, you know, you have much better odds of them allowing that external control to be utilized.
When would you have this discussion next year? Have you scheduled the meeting with the FDA?
Not, not that meeting. We've, we're, we're in the process of scheduling the first meeting that should happen, early Q1. That's the double-blind placebo control discussion. Once you have that meeting, then we'll have the second meeting, which is the external control stat plan meeting. We expect that meeting to happen right in the middle of, of somewhere right around Q1, Q2. You know, February to April-ish. You know, that's, and then if we have success in that meeting, then we have a third meeting. That third meeting, you know, you have to have that, you can't have that third meeting without the first two going right. The third meeting is, "Okay. We've agreed on the external control and stat plan. We've agreed that the double-blind placebo control trial can be a registrational trial.
We can also potentially use that for confirmation study in the United States. Then, we say, "Okay. Third meeting would be, how much data do you want? You know, do you want 60 day patients' worth of safety data? Do you want, 15 patients at one year? Tell us the number." Then we'll just run off the time. Then we'll know when we can file. You know, the hope is we can file, late next year, you know, start rolling submission, late next year.
We would know by mid-year, I guess.
Yeah. You should. Yeah. Right around there.
and then you know, once you have that plan in place, you'll run the analysis on, on the thirty patients.
Yeah.
Will you be sharing that data with us or is that gonna be?
You know, I'll have to wait and talk to the board and everybody in the executive team. I know that y'all would want data to get confidence. You know, I know it's important. It's not like I would hide it for any other reason.
You know, Bo, you talked about, you know, the queue. You know, there is right now a holiday pause. Early next year, are you gonna restart the?
Yeah.
The four to seven-year-olds would, would be enrolling?
Yeah. So it's all we're enrolling three groups right now. Cohort one is basically four to seven. Then we're, I mean, four to six. Then we're also enrolling cohort two, which is seven to less than 12. We also enroll in cohort three. I think that's a very important cohort, especially when you're thinking about regulatory strategy and Sarepta. You know, that cohort three is ages 0, 1, 2, 3. We've dosed two boys already. We've dosed an 18-month-old. We've dosed a 20-month-old very safely. Those are exciting times because there is no label for that age group. There's 1,600 little boys in those, you know, 0, 1, 2, 3, 4, and so, or 0, 1, 2, 3. We think that that's a huge opportunity.
That's about $4.5 billion with Sarepta's price tag. You know, the kids need to be there. We've dosed in that. So we'll have safety data. And then we're hoping we can get a label there.
And when would you hope to dose, you know, older boys?
We're gonna be cautious there.
Both ambulatory and non-ambulatory?
Yeah. Yeah. That's greater than 12. We're gonna be real cautious. I know I have a safe drug. It looks well. I, yeah. I say that. It's gene therapy. I've dosed, X number of kids to date. I have, as we sit here today, no drug-induced liver injury. That's even the boys that we've dosed, you know, just a couple weeks ago. I feel really good about the drug. Going into those older, heavier, sicker boys, that could, I wanna go hand in hand with the FDA on that. I don't wanna harm the drug I have. I know that those boys and those families need a therapy. I am committed to getting that therapy to them.
However, I wanna do it hand in hand with the FDA so I don't screw up the label in case there is an issue in these older kids, older, sicker kids. I think that's a discussion with the agency down the road.
Got it. Got it. On the safety side, you mentioned you haven't seen any liver events. I think there was one grade three myositis.
Yeah.
Can you talk a little bit about that and what were the learnings from that patient?
Ironically, we hit a hotspot that was unknown. Turns out it was known. It actually showed up in the new Sarepta label, recently. It was deletion 59 through 71. It was unknown until for us. You know, we did not exclude it. And basically, you know, we're producing, we produced a protein that the body rejected. You know, that's just why all these companies, all of us, us, Pfizer back in the day, Sarepta, you know, REGENXBIO, we exclude certain deletions. We got very lucky with that boy, because it was very mild. It was basically face. It was, you know, lips, mouth, eyelids. That was the extent of his myositis. Myositis cases can be very severe. You have to treat them like they're going to be very severe. You know, so you don't take any chances.
We got very lucky with the little boy. We hit a hotspot. We've excluded the mutation. Ironically, in the updated Sarepta 11, that exact mutation showed up. That means they must have had a case as well. I have to assume that because it's the first time that we've seen that mutation. You know, we're out there telling everyone because I hope, you know, REGENXBIO and anyone else who wants to treat those boys, they should probably exclude that hotspot.
Got it. Got it. And so that's, that's the plan going forward, even, even for your studies?
Yeah. Yeah. Yeah. We're not gonna dose that mutation. It's less than 1%. It's like, it's a very rare, very large mutation and very rare.
You know, on the discipline expression, you've disclosed, I think, about 10 patients' worth of data.
Mm-hmm.
To date, will we get an update on that?
Yeah. The expression data, we'll provide updates on, you know, because I really think the FDA really cares about the clinical sort of endpoints. Expression, you know, we'll provide an update on that and all the biomarkers that we have. We're very excited about the data. It, you know, it seems like it's one of the most robust, if not the most robust program to date from expression. We're just gonna keep dosing. We'll see how it plays out.
You know, you had a few outliers.
Mm-hmm.
In the data. What were some of the key learnings?
We're gonna share that, those key learnings, probably right around the MDA conference. It was definitely, when we saw the data, it definitely caught us off guard because these three boys were different than the others. So, you know, you can just chalk it up to heterogeneity or you can do a deep dive. We did a deep dive. We looked at every possible scenario. Was it weight? Was it age? Was it mutations? The answer was no. We found a signal that we believe is important. Probably not just important for us, but maybe important for the entire field. It's really right around how you treat that day one, day two. It looks like this capsid is pretty unique as well.
Gabriel, our Chief Medical Officer, we go back and forth. Is our findings just important for our capsid or is our findings important for AAV in general? We will find out because I will share it with everybody. We are following some method of use patents right now on how you use our SLB101, how you dose it that day one. The reason we are following these patents is because we have, we believe that this capsid, well, it is not just we. With the KOLs, believe that this capsid is going to end up being the workhorse for gene therapy for decades to come. That means there is going to be a lot of programs. I think we have 30, you know, in our last press release, either academic labs, small companies, mid-sized companies that are using this capsid now.
Our findings in Duchenne will help them because it's all about how you dose. It looks like this capsid transduces and expresses very, very quick. By day four, it's out of the blood, and that's a finding that has never been seen before. We have our own control. Remember, Solid had its first generation program. We looked at the blood. We looked at actually plasma for those boys. We looked at whole blood for our boys. The amount of virus that's in the bloodstream, at day four, it's gone. In old first-gen programs, AAV9, it's very, very high. Why is that important? If you think about aHUS or TMA, you know, you dose these kids with AAV, you see the C3, C4 move, you see C5b-9 move.
You do not ever get to this tipping point of aHUS or TMA. Why? We think it is cleared. By the time the body is really looking to remove the antigen, it is no longer there. I think this is very unique to AAV. I think a lot of people are gonna take notice to it, a lot of gene therapy companies and academic labs 'cause this could be a huge thing for the field.
That's great. And so you hope to file a patent on this.
Yeah. It's method of use patents. It's just really around right around how we dose. At the MDA conference, we'll share our findings.
Are you gonna modify your dosing in the trial as a result of this?
We did.
Oh, you have?
Yeah. We did.
And in the randomized trial as well?
That's correct.
Okay.
Yeah. We only use steroids, just to be very clear. Steroids only. We do not use sirolimus. We do not use eculizumab or rituximab or anything else. It is just steroids. It is just how you dose.
Are you implementing that also in the FA and CPVT programs as well?
We are. We are.
Can we talk about, the CPVT is an asterisk because we use AAV8. And AAV8, we're gonna use sirolimus and eculizumab with AAV8 because of the history and, and just, you know, it's first-generation capsid. We plan on creating now that we know what we have with SLB101, we're gonna create a second-gen CPVT program. We're gonna get proof of concept, proof of data in our first-gen, three, four patients. And then we're gonna flip it into SLB101.
Got it. Got it. Both of those programs, have they started patient dosing?
We just did a press release, I think, what was Monday?
I'm looking at Nicole back there. Monday, for orphan disease and rare peds. We announced that we are screening now. We should be, I could have probably pushed it and dosed over the holidays, but it'll be early January. First patient dosed early January.
That's for Friedreich's?
That's for FA, yes.
That's for FA.
CPVT would be Q1. We have 30 patients lining up for CPVT. I think out of Mayo alone, we have like 15. We have a lot of patients actually lining up for CPVT. I've been a little slower on that one. I've just truthfully, I've just been trying to conserve some cash because I know what I have with Duchenne. And I need, need to extend the runway just a little longer, to get some of these inflection points. I've just been a little cautious on that one. Basically, we'll have three drugs in the clinic in the next probably, you know, two months, you know, three different disease states with patients being dosed. FA, I expect early January, CPVT somewhere in that January, February timeframe. And then Duchenne is just, you know, lights out.
For FA, could we see some data by second half next year, first couple of months?
I think so. I think we'd be dosing. We'd be doing basically what we did with FA. I mean, with DMD, dose three boys or boys. Dose three patients. It'll be both boys and girls, for FA. And then we'll release the data probably three, four months after the fact. You know, safety update might be a little faster, because if I think if, I think if I dose three patients safely in FA, I think the world will take notice, because it's such a unique program. Everybody knows the impact of rituximab in the cerebellum. And we're gonna be the only one that has, can get to the cerebellum, get to the spinal column, get to the heart. If you think about the future and how we think about FA, right now during clinical trials, we'll be dosing patients that are older.
Some will have cardiomyopathy. Some will have just CNS. Realistically, you want to get to a point where you dose a five-year-old that has no idea what her journey's gonna be. You are the only drug of its kind that can actually get to the cerebellum, the spinal column, the heart, all the areas that are affected will be this program. I expect bumps in the road with a lot of chatter, you know, competitive chatter at the beginning. I think long-term, when we look out into the future, this will be the only program that you can not only dose any patient wherever they are in the journey, whatever their disease is, but you can also get down to that four or five-year-old when they first get diagnosed and hopefully stop the disease forever.
It is the only one of its kind that's gonna be able to do that. I think that that's where the vision is, not about the next three years or so.
What's a good surrogate endpoint, for FA?
Yeah. It'll be mFARS, but it'll also be speech, you know. We can do, and the speech is, you know, relatively easy. They just read a paragraph, each and every time. You just monitor it and videotape it and look for speech recognition, use speech recognition software, speech, swallowing, mFARS, cardiac output. There's a lot we can do here. You know, the data will be rolling in over time. I'm pretty excited. I think you guys should all take notice. If I can dose three patients safely and announce that, I think everybody should sit up.
I think we're about out of time. Really appreciate.
Yeah. Thank you.
All of your insights and comments on the program. Looking forward to exciting updates.
Yeah. Thank you, Biren. I thank you for inviting us.