Everyone, we are on day two of Citi's Biopharma Back-to-School Summit. I'm Yigal Nochomovitz senior biotech analyst here at Citi. This is one of the final sessions of the day, but it is certainly a super important one for sure. My pleasure to have with me Solid Biosciences and the President and CEO, Bo Cumbo. Welcome, Bo. Thank you. Thank you. Very much for doing this. You have a lot going on, obviously. Maybe just to set the scene, if you could give us a high-level overview of the pipeline, what you are doing in DMD. Of course, Friedreich's ataxia is super important as well. You have a very important set of updates coming up in the fourth quarter, both in terms of regulatory and data. Love to hear more about it. Yeah. Thank you, Yigal. Thank you, Citi, for the invitation. Great to be here. We are very excited. I think for those of you who do not know, Solid Biosciences is a precision genetic medicine company. We focus primarily with AAV at the moment. Two disease states we put almost all of our resources and personnel to is DMD and FA, Friedreich's ataxia and Duchenne muscular dystrophy. We are heading into a very interesting time over the next, let us call it, half a year for Solid Biosciences. We have multiple inflection points. The first one in the next couple of months is we are going to be holding a meeting with the FDA to talk about Accelerated Approval, to actually show them some of our clinical data. It would be the first time that actually we have shared and actually looked at as well as analyzed and then shared our clinical data. We will be doing that in the fall with the FDA and talk to them about a pathway for Accelerated Approval. Then after we have that meeting with the FDA, which should happen in Q4, we will update the Street and provide them, the Street, not only our clinical data that we shared with the FDA, but also the sort of regulatory discussion on what is our path forward, if we have one, and how we are going to move based off the information that we have. We also have Friedreich's ataxia. We have already dosed our third patient. Planning patient number four in September, patient number five in October. That is currently scheduled. That means you guys, the Street, will have at least three patients of mFARS data in Q1 or really first half of next year, but most likely Q1 of next year. Then you will have some extra safety data from a couple of patients as well, as long as we can dose patient four and five. Very excited about that. I think it is an exciting couple of months for Solid. Okay. Well, I know you cannot speak to too much detail in terms of the actual data, but can you give us a sense for the types of data and sort of the magnitude of data in terms of how many patients you might expect to learn about for DMD in the fourth quarter? Also, I know you still have not had the conversation with the FDA, but if you can kind of enumerate what you might see as the differential scenarios there in terms of how things could go forward with the feedback from them. Yeah. Let me backtrack and let us start with the end of 2025 so we can get here so you can figure out how we got here and then where we are going to go going forward. So at the end of 2025, the very end of 2025, we submitted a statistical plan, a SAP plan on basically the rules of how we were going to look at natural history data and do our data comparison for our INSPIRE trial when we actually had our clinical data. We also, at the end of 2025, early 2026, talked to the FDA about how we were going to set up our phase III clinical trial design, that is called the IMPACT trial, as well as our endpoints that we were going to look at. I think that's critically important because those endpoints are going to be the ones that we're going to talk to the FDA about in the fall. In March, we had another meeting with the FDA. We established that there's still a high unmet need in Duchenne. This sounds trivial, but realistically, when there's an AAV gene therapy that's got full approval, you need to make sure that the FDA acknowledges that Duchenne still has a high unmet need. They did, and they also acknowledged that our drug is novel. That's also important when you think about just making sure that they don't view all the gene therapies as a me too. Our drug, our proteins are novel. But during that meeting with the FDA, we started talking about a hypothetical situation of how we're going to look at our data, and also Duchenne videos. We got back and forth with the FDA on that. They gave us a couple of ideas. We had to go back and modify our statistical plan, our SAP plan, based off that conversation. That means how we were thinking about selecting the data and being able to analyze the data going forward. That SAP plan was submitted in late July. Now we are pulling all our natural history data in. We will be using the SAP plan of how we are going to analyze the data and select the data that's going to be used in the clinical analysis. We're pulling our clinical data in. We will be creating a dossier, a briefing book for the meeting. We'll be requesting the meeting very soon, and then meeting with the FDA in the fall. What are we going to talk to them about the endpoints, to your question. It's the ones that were already listed in the IMPACT trial for the phase III, time to rise, Stride Velocity 95th Centile, and then we have a couple of their endpoints like four-stair climb, 10-m walk/run test, and we'll utilize those to create the data package. How many patients will we have? First you have to understand we dosed 53 patients, all safe, all the way down to age six months, all the way up to age 10. Those patients are ongoing. We are only looking at patients that have at least hit 365 days, one year period of time. Basically, when you have the meeting with the FDA, you have to cut your data about five months ahead of time. When we've cut the data at day 365, we're going to have a little over 12 patients of data for the FDA to review that has at least one year. A couple of patients will actually have up to 18 months. But at least 12 patients, slightly more, to discuss with the FDA. More data continues to roll in over the course of this year, but we won't be able to import that into the briefing book. Okay. The goal there, I gather, is with those 12 patients, as you point out, to be able to make a statement around functional benefit that would support, in your view, assuming you show that in a pathway for Accelerated Approval. Is that correct? Yeah. What you want to do is you want to look for clinical benefit. Remember, what's the FDA have to do here? The FDA has to make a judgment call. They actually wrote that in our meeting minutes the last time. Accelerated Approval is based off a judgment call of the totality of all the data. And we have a whole bunch, as you know, a ton of biological correlate data looking at anything from Western blot all the way down to muscle integrity biomarkers such as embryonic muscle, heavy chain, titin, et cetera. But they want to see clinical data, and so now we need to show that the drug is actually doing something in the patients that have had biological correlate data. It's not just it can be Western blot, it can be mass spec, but it also can be some of the biological correlate data or a whole host of data set looking at patients that are moving in a manner that's different than natural history. And you just have to make a judgment call. It has to be directional in nature. Because for one, our trial is 18 months, the INSPIRE trial's an 18 month, but we're taking an interim look at 12 months to give the FDA some data. So directional in nature, clinical benefit based off biomarkers, including Western blot, mass spec, et cetera. All of that data in totality, along with our phase III that is up and running, that is a double-blind, placebo-controlled, multi-country study. That should give the FDA a lot of confidence that they can make a good judgment call, that maybe we can have a pathway for Accelerated Approval, and that's we're hoping for as we move forward. Okay, so it doesn't necessarily have to be, since it's a small sample size, to be statistically significantly different versus natural history necessarily. That's correct. You have to be able to show some clinically valuable separation that sort of meets the overall litmus test across all these different. Yeah. They have to make a judgment call, and they have to have confidence in the dataset that gives them enough data to make this judgment call. It's also great, by the way, that the new CBER head's in place because I think when you're having to make a judgment call, you definitely want leadership in place so you can actually bounce ideas off them and sort of get their support. Having the CBER head now in place, I think is as beneficial for us as well as we head into the meeting. Everyone understands, at the moment, you're in the active process of doing this analysis, so you don't necessarily have all the answers today. Oh, no. Yeah. No. We were in the process, but we don't have all the answers. Yeah. Okay. We're pulling all the natural history data in. You have to QC all the data. For the natural history, you have to run through the statistical plan and sort of requirements because a lot of the natural history data won't be utilized because it doesn't meet the requirements that were placed in the SAP. Then you have to get your data to come into the in-house. You have to QC the data, then you have to do the comparisons. You run a bunch of different comparisons, and then you put your briefing book together. Yeah. We haven't even scheduled a meeting yet. We're getting ready to schedule the meeting in about a month. Then you have to submit your briefing book 45 days in advance of the meeting. So we still have a little bit of time to do this work. I know. I appreciate you're in the middle of it, but qualitatively, can you give sort of a sense as to, for example, with time to rise, like what might be a good result relative to natural history? Is there a way to— There's not a way. There's not a way for me to actually— Okay. —qualitatively or quantitatively give you an answer on that because I don't know exactly what natural history's going to say. You don't know that yet either. Okay. You're trying to beat natural history, and I don't know exactly what natural history's going to say for the subset of patients that we're actually— Okay. —made it 12 months. We've dosed anywhere from ages six months to 10 years of age, so there's a whole range. But you're trying to do like age matching? You are, and that's why it takes a little bit of time. Yeah. That's why I couldn't give you an answer. Understood. Okay. That's obviously an important, and that meeting with the FDA is in the fourth quarter. Yeah, it'll be in the fourth quarter. And then— We plan on hitting that timeline. Somewhere, I gather like— 30 days later, we will get the meeting minutes. As soon as we get the meeting minutes, I go to the board of directors, make sure that they are cool with it, then we are going to release all the data and sort of the regulatory update to the street. Okay, so it sounds like back half of 4Q 2026 is a more likely time. I would say back half of 2026 to very early 2027. Okay. Got it. All right. Very good. As far as the study, the confirmational study, confirmatory trial, the IMPACT DUCHENNE trial, where does that stand in terms of its rollout today? Yeah. We are still waiting on Europe. We do not have Europe up and running yet. Right now the only two sites that we have, Australia and Canada. Enrollment really will not pick up until we have all the European sites. We have Belgium, Italy, I think, France, U.K., Spain. There is a whole host of countries that need to get up and running. That should happen at the end of the year to early next year. Then we have a couple sites in the U.S. for kids that are traveling from abroad. They do this sort of healthcare tourism. They obviously cannot get reimbursed for ELEVIDYS because they are from overseas, but they would like to participate in clinical trials. They come to the U.S. for healthcare. These tend to be the sort of kids coming from families that can afford it. We will set up some sites in the U.S. That will happen at the end of the year to early next year. We will set up all the European sites, then enrollment really enhances after that. It is also important that we are going to meet with the FDA in Q4, if something comes out of that, then we can also modify the trial if needed based off the discussion with the FDA. They are obviously, as you said many times before, already aware that you have initiated that study and done the— Yeah. We met with them, as I said, December-ish of last year, 2025. Talked to them about the phase III. We sent them the press release when we enrolled the first patient, that was somewhere like May of this year or something like that. Okay. They're aware. Yeah. Do you want to offer any thoughts in terms of what happened with Capricor and how that shook out with the FDA? What lessons did you learn or not learn there in terms of what the FDA is looking for in a DMD package? Well, one, I found it great that they're actually continuing to communicate and review the data. I think that shows a lot of flexibility. Obviously, you had the AdCom, you had all the debate around it, yet the FDA is still communicating and working with the FDA. I actually think that that is a good sign, not just for Capricor, actually just for rare disease. Having the flexibility or having the willingness to actually communicate and talk through the data. Because some of these rare disease packages are very challenging, especially in kids, young kids, Duchenne kids, cardiomyopathy or young looking at POL. I think these are very hard diseases and it takes good communication. I'm actually pleased to see that they're still talking. I think we did learn some lessons on how you think about setting up your phase III, how you think about. We didn't just learn it from Capricor. We actually watch all the trials, all the trials that are ongoing, and the lessons learned, not just in Duchenne, but all the rare disease trials and how the FDA communicates around them as well. We try to always do the best thing we can. We know that this is an open label study. We know that the FDA doesn't like some of these endpoints because they can be effort-based in an open label study, and you worry about bias or coaching or training and anything, all this stuff. By the way, that's one of the reasons we love Stride Velocity 95th Centile. It gets away from all of that. Stride Velocity 95th Centile is a great endpoint when you want to tie it back to another endpoint, like a functional endpoint, and just say, "Hey, look, here's two endpoints, one functional in nature, one effort-based in nature, one that has no human touch whatsoever in Stride Velocity 95th Centile," and you can show sort of comparison. If you have those two approach, I think that really helps with the FDA and hopefully we're going to try to do that, all of this, and create the best package we can, knowing there are limitations to the data. Okay. Presuming you get good feedback and they say, "We agree, we think you should file for Accelerated Approval," how quickly can you get that filing together? Yeah. All right, in that scenario, and that's the A scenario, right? In that scenario where they high five us and they say, "You're good to go," which the FDA never does that, but if they do say that, then we're in the middle of PPQs at probably the CMC that's the last to file. We're in the middle of our PPQs. We've done our PPQ1, PPQ2's done, PPQ3 is underway. We'll probably have all that data in by end of year. That means we need to meet with the CMC part of the FDA early next year to go over that data with them. Then once if the FDA is good with our three PPQs and everything looks good, then we'll start making the CMC module, and we could potentially have the CMC module completed over midsummer. Then once we do that would be the time that we could file the modules. But so interestingly, for example, if they say, "Great, go ahead, high five. Yeah. They don't do that, but anyway. Let's say they say, "Okay, well, 12 look good, but we want to see 24," for example— Yeah. —which is not inconceivable. Right. Actually, I think that's— You could accrue that while you're doing this, right? Could it be concurrent? Well, that's the great news. We dosed 53 kids. Yeah. They're already dosed, so every single day is another day that they're just gathering data. Yeah. So in a scenario where the FDA says, "Hey, listen, we really like your data. However, we really want 25 patients worth of data," the great news is those 25 have already been dosed. You guys, all the investors, we were pretty transparent, actually very transparent on all our safety last year and this year, and we updated our press releases, our presentations pretty much on a monthly basis, and you could see the ends. So basically, you guys can pretty much track exactly when we dosed 25- 30 patients. I will just go on and give you a heads-up that we actually released a press release very early in 2026, and we basically said 25 patients had been dosed by the year-end of 2025. It was 25- 28, something like that. So if they kick it out to 25 patients, yeah, that's three months. Right. It's not bad at all. Yeah. That's the great news with dosing 53 is it's just sort of like there. The data's going to be rolling in over the course of the next couple of months. I guess it's hard to really have a lot of insight into that number, right? What they want. No, you got to have the meeting. Yeah. You have to have the meeting. You have to talk to the people. You have to understand how they feel about the data. Duchenne is tricky, and obviously you can see it from all the other companies. We don't want to get ahead of the FDA. Let's just have the meeting with them, hear them out. We are going to push. We are going to push. If our data looks good, then we are going to push, so let's see what happens. Okay. All right. Let's talk about another important rare disease, Friedreich's ataxia. Yeah. Obviously it's good to see there's been some progress in that field, and where there is an approved drug, as we all know. But your approach is potentially more on pathway in terms of restoring the missing protein. First of all, just tell us about SGT-212 and how it works in terms of the dual mode of administration. Yeah. We are very excited about this. We wanted to make a drug that we could meet the patient wherever they are in the course of their disease. As you think about different types of patients, different phenotypes, patient that's 40 years old, very severe, needs help in the heart, needs help in the spinal column, cerebellum, we'll have a drug for them. Hopefully, then we go down to, like, a 20-year-old. Maybe they have plus or minus cardiomyopathy, spinal column somewhat intact, the cerebellum's intact. We have a drug for them. Or a six-year-old. Six-year-old, they're definitely not going to have any cardiac symptoms yet. You really have no idea of the course of her disease, and we will have a drug for her. That's the goal long term for this study. Right now what we're doing is we're studying really the sickest patients. We're studying the non-ambulatory patients that are pretty well advanced. Our first two patients were mFARS of 80. To put it in perspective, 93 is the worst of the worst. Third patient was dosed in August, and she was mFARS in the 50s, low 50s, so a little less severe, but still pretty severe. We have two additional patients that are coming up. What we're trying to do is dual route of administration. What does that mean? That means that we first go right to the heart of the problem, which is the dentate nucleus of the cerebellum. We dose that patient using an IDN stereotactic approach. It's an MRI-guided approach, so we can actually see the coverage of the dentate nucleus in real-time as we're dosing the patient. We use an enhancement agent so we can see through the MRI exactly how much we're covering. We wanted to cover roughly 15%-20% of the dentate nucleus. We're covering a lot more than 15%-20% of the dentate nucleus. We've never disclosed that number for our first three patients, but it's significant. Then we let the patient rest. That procedure, just to let you know how that procedure works, from the time that they walk in to the time that they finish, it's about four hours. Realistically, the surgery itself, because you're only going the 3 mm in, you're only doing about two hours of surgery. So it's in and out. It is done. That two hours of surgery means from the time the needle goes in to the time the sutures are all sutured up, you're done. They rest for about an hour, and then we give them the IV dose. Eventually, this is going to be outpatient dosing. We'll have multiple clinics across the country that'll be doing this. We already have three, which is Ohio State, UCLA, and CHOP or Penn, and then we're going to basically open it up to additional sites. Additional sites for our phase III trial. What are our goals, just so you understand? We've dosed three. We're getting ready to dose, hopefully, knock on wood, patient number four in September, patient number five in October. We're hoping for two additional patients by year-end to give us seven total. That means we can meet with the FDA sometime in the first half of 2027, and we can provide them the data and start talking about a registrational trial. If we have a path forward for a registrational trial, this will be a real placebo-controlled trial. Why? We want to make sure that we not only get approval in the U.S., but we also get approval ex-U.S., and we get reimbursement ex-U.S. Friedreich's ataxia is bound to affect us out of Europe. It's a huge population. It's bigger than the U.S., and we want to make sure we can get this to all the patients that are needed. So we would hope to start that trial end of next year, end of 2027, and get it up and running. So we have sometime next year, if everything goes well, we'll have a phase III in Duchenne and a phase III in FA. How big a phase III would you need? That's depending on what the FDA says, but it doesn't sound like it's going to be a very big trial. Yeah. Realistically, it all comes down to the powering, right? The powering, if you think about mFARS, just natural history, you always go up and to the right. You always move, unfortunately, they always progress. The mFARS never stops. Depending on your average mFARS baseline, you can sort of pick and project how many points they should increase over the course of a year to a year and a half. Then with the first 7- 10 patients that we dose, we'll understand what are mFARS, whether it's a pause, whether it's a reduction, whether it's just a slowdown, understand that trajectory, and then we'll be able to power the study. My guess, my rough guess, it's no more than 50 patients in a double-blind, placebo-controlled trial. That's guessing without actually having any data. I have no data that tells me right now of the impact of our drug on the first 10 kids because, or 10 patients, because we've only dosed three, and they've only been out for a short period of time. But we'll be able to power this and power it against natural history, and then we'll figure out how many patients we can have. Well, for the initial seven, what's the time point where you're going to measure mFARS for the first point? 90 days. 90 days. 90 days, yeah. Some of those three are just getting there now, or not quite? Well, patient number one was dosed in January. Patient number two— Okay. —was dosed in March. Patient number three was dosed in August. So— There was a gap in between March and August because we had three back-to-back-to-back screen outs due to heart issues. They didn't make the background. They didn't make the criteria to get into the trial. That delayed us about two or three months. We have three patients, different time points, so we actually have some decent. We're going to have some decent data for you guys in Q1. For those first two, you have some initial— Yeah. —clues, I gather. Okay. We do. Okay. For the placebo, what is it going to be? Because it's going to be like a sham procedure. So— How are you going to do that? —it's a placebo/sham. It's a placebo in the arm, obviously, for the IV portion of the dose. Yeah. A little sham. You don't do a burr hole. You don't do any. Yeah. It's just a little nick on the back. Because actually, when the patients actually do the surgery, all they have is, if you cut yourself shaving, you have the little round Band-Aid. That's all you actually have here in the trial. They don't really feel it, and it heals very quickly. You wouldn't have to do a burr hole or anything like that. It's really just a sham cut with a little Band-Aid. Okay. Another important question is, it's a small study, so it could potentially be sensitive to the splitting in terms of who gets the severity on both arms. Is there a correlation between the rate of progression of mFARS and the absolute value of mFARS? Meaning, do you want to make sure that— Yeah. —the average is kind of similar across? Yeah. No, 100%. Because depending on where you start, if you start lower, you actually have more point, you lose more points per year. Faster, yeah. If you start at a 20 or a 30, you can lose 4- 6 points in a year. If you start at a 40, you might lose 3- 4 points a year. You start at 60, you might lose 2 points a year. You start at 80, you're going to lose about 0.5- 1 point a year. And so where you start absolutely depends on sort of like the, how many points you're going to lose over the course of the year. This disease is, while it's heterogeneous, it's very relentless. It always marches up to the right. To your point, it's very important to get the baselines correct. As far as I understand, we've talked about this in prior sessions, even if you see a slowing of the progression, that would basically be a positive. Yeah. Look, let's just take an mFARS of 80, right? The most severe person possible, 80- 90. It's very hard to actually even tell a difference between 80 and 90. 93 is the most severe, but at 80, they're in really bad shape. So they lose about half a year. That's on the conservative route. You could actually say they lose a point, let's just say half. If you can just pause for one year, you delayed one full year of progression. If you decrease even a point, you sort of reverted back two years. You sort of gave them basically two years of mFARS decline back, or increase back. So yeah, so no, it really does matter. If we can just slow this disease down or pause it or change the course of mFARS directionally, it could be huge. It could be huge for the community. You mentioned the placebo-controlled trial, which would support the global approvals. Is there a scenario where even with the seven, if the data look really good, that there's an Accelerated Approval pathway, or that's— I mean. —too much of a stretch? We're not going to go into the FDA and ask. Yeah. Right now, actually, I don't think it gains us any time. I think if we can go into a really well-thought-through placebo-controlled trial sometime next year and goes relatively quickly. Just thinking through the bureaucratic process of working with the regulatory agencies, especially in Europe, it would be more beneficial just to do the trial the way we were thinking about it. We'll bounce the idea off the regulators. If we see something that is just remarkable in nature, then we'll talk to them. We're not there yet, clearly, and so we'll have to wait. But right now, our thought process is we're going for full approval. The Europeans in particular, they should be okay with the placebo? Because I know over there's some questions around that. That's correct. That's why we're going to do the trial in the U.S. Oh, you're only going to do U.S., okay. Yes. All right. Do you want to speak a little bit about the platform very briefly? Because you do have the capsid platform, and you have a lot of licensing agreements for the technology. That doesn't get a lot of air time, so. Yeah, no, we're very fortunate. I think we have a great capsid in what's called POLARIS-101 now. It used to be called AAV-SLB101. It's called POLARIS-101. We have 50 different agreements, either whether academic labs or small companies wanting not only our capsid but our dual plasmid sometimes talking to us about our promoters and manufacturing capabilities. Long term, we believe this POLARIS-101 capsid will be the dominant capsid in any of the cardiac or skeletal muscle diseases that are using AAVs. We're already seeing universities shift away from 1st-generation AAVs and move toward POLARIS-101. We're open for business because we want to actually change the course of gene therapy, make it investable again, get a lot of companies that are out there that are smaller that can't afford the $10 million capsids. You should not go back to the AAV8s, AAVrh74s, AAV9s, first gen capsids because we know what you're going to get, and we know what to expect there. So why not try POLARIS-101? We're working with multiple companies. We're working with multiple academic labs. We have other capsids too. We create all our capsids in-house. We create them with either AI on one side, or we hand-make them on the other with using RGD peptides and inserting peptides and making small mutations. So we have two different type of capsid platforms all coming together. Our next capsid looks like it's called 282. We'll name it soon, and we're going to license that capsid out as well. I think we have four or five other capsids that are going through non-human primate work right now. We'll have all that hopefully by year-end. We're going to present some of that data very early next year, and hopefully it'll change the trajectory. To your point, Yigal, no one's paying attention to it. What's going to happen in three to five years while everyone's focused on Duchenne, everyone's focused on FA, all of a sudden you're going to see 100, making the number up, 100- 200 programs coming out of academic labs using Solid inside, Solid technology inside. Then the great thing is that royalty stream will be coming down the road. So long tail, and while everyone's going to get their big inflection points hopefully on Duchenne and FA, then all of a sudden the capsid platform really kicks in in year three, four, five, six. Okay, one more. You already touched on it. You mentioned AI being used to design some of the capsids. Is that the primary usage of the AI tools at Solid, or are you using it for other things like preparing filings, analyzing data, summarizing? We are building it internally for ourselves. We have a third party that is helping us build it. What we want to do is we want to analyze all our preclinical data, all our CMC data for every single batch, all of our clinical data compared to natural history, and be able to run this for each and every program. We are also allowing some of our customers that I just mentioned on our capsid platform to pull their data into our networks, and help them analyze their data. The AI platform actually helps write all the regulatory documents. Anybody that uses our capsids, they can leverage our non-human primate data. They can leverage our mouse data, all the GLP tox data. It could help them get through regulatory process quicker. If they use our platform, our AI platform, insert their data into our platform, then actually they can leverage other people's data as well. It is all anonymized, so they get to keep their data, but they also get to leverage all the data that we are building. We are going to be doing that for all our customers that are using our capsids. All right. Very good. Well, thank you very much and a lot to look forward to for the balance of the year and beyond. Thank you, Yigal. Sure.