Good afternoon, everyone. Welcome back. My name is Arthur He, Senior Biotech Analyst at H.C. Wainwright. Thank you for your joining us, for have a conversation with Bo Cumbo, the President and CEO of Solid Bio. Bo, thank you for coming. Yeah. Thank you, Arthur, and thank you, H.C. Wainwright. Maybe Bo, for the audience who are new to the story, could you give us a two-minute version of your company, where they stay today, and where you expect to be in the next 12 months, I guess? Yeah. Thank you again. Solid Biosciences, we're a precision genetic medicine company. Our current platform is AAV gene therapy, and we focus on two main diseases, which is Duchenne muscular dystrophy as well as Friedreich's ataxia. We also have multiple other cardiac programs that are not in the clinic yet. We have them ready for the clinic, or one's actually in the clinic for CPVT, and other ones are getting ready to be in the clinic for TNNT2. But we're slowing them down. We're putting all our resources right now, head count money, toward the two main programs, which are Duchenne muscular dystrophy, it's called 003, and then Friedreich's ataxia, it's called 212. We also have a capsid delivery platform in which we make capsids to change the course of delivery for gene therapy in general, and we work with academic labs to make sure that they have access to these tools. As new programs, as these institutions are making new programs, they're using the next generation technology instead of having to revert back to AAV8 or rh74, et cetera. Very excited. Next couple quarters, big quarters for the company. We're going to be meeting with the FDA on one of our products, and then we're continuing to dose the FA program, which will lead us to an FDA meeting sometime in the first half of next year, and then we'll talk about a registrational trial for that program. Very exciting next six months or so. Thanks, Bo. Obviously the 003 is not the first microdystrophin gene therapy to reach the clinic. Could you tell us a little bit more how different of the construct and the capsid for the 003 and how that could be potentially translating to the clinical wise? Yeah. We're really excited about our program. Just to put it in perspective, microdystrophins have been around for a while, different versions of it. Jeff Chamberlain, Dr. Chamberlain out of Washington, created most of, if not all, of the microdystrophins that are out there, and he kept refining this over many, many years. Realistically, the last one that he settled on, the one that he felt was the best one is the version that we're using in 003. Why? Many of us, all of us in this room, we have a very long protein dystrophin, but all the companies are actually shrinking it down. When you shrink it down, you have to think about what you're putting into that construct. We removed all the hinges, so we only have two hinges, and that gives the protein as much flexibility as possible when you're shrinking it down and it's entering in the tissue. Then we kept R16 and R17. Those are the repeat domain, R16, R17, so that way we can recruit for a protein called alpha-syntrophin. When you recruit for a protein called alpha-syntrophin, you can recruit and bind alpha-syntrophin to nNOS. When you have nNOS, it increases your blood flow, it decreases fibrosis. We also recruit for a protein called cavin-4 that increases calcium channel handling. We believe that this protein, this construct, is going to be the best one for the children as we increase microdystrophin. We use a new capsid that has never been used before, first in human, called SLB101. We call it POLARIS-101. This capsid was created in the lab. Each capsid has about 60 of these RGD peptides. The peptides bind to two integrin receptors that we all have in our skeletal and cardiac muscle. We haven't really disclosed what those receptors are. Some people have guessed from patents. We try to keep it as quiet as possible, and because we're building an entire platform around these integrin receptors. But in this capsid, when you look at this capsid in both mouse model, non-human primates as well as patients, it looks like it has a broader distribution in muscles. So depending on the muscle in the mouse and the non-human primate, 3x- 5x greater biodistribution than AAV9, like the diaphragm's 5x- 10x greater. Human cardiomyocytes, you see expression about 19x greater, so it's really tropic to the heart. In humans, in the mouse, the non-human primate, and we believe in the humans, it's liver detargeting. You saw it in the mouse and the monkey. Of course, you can take down the mouse and the monkey. In the human, obviously we don't do biopsies in the liver. But what we see is ALT, AST decline from the time of dose. ALT, AST decline immediately. It goes down and to the right, and GGT stays flat the entire way. With those 53 boys, we see this trend continue. It's on our slide deck. You guys can go look at, the whiskers are there, and you'll see ALT, AST go down. And why is that important? Well, we can use that ALT, AST now for a biomarker for muscle degradation and destruction. And so these kids, they come in at baseline 300, 500 ALT, AST at baseline. That's not due to liver, that's their skeletal muscle breaking down. And now we can track it. Because it's where we're retargeting, we can sort of watch ALT and AST decline, and we look at a whole host of biomarkers, and that gives us an idea that there's a lot of muscle integrity, that the muscle is shoring up. And that gives us confidence that long term, we're going to see clinical benefit in these kids. We're feeling really good. We've got to meet with the FDA in Q4, and then we'll understand what we have and what they think we have. Let's stick a little bit along for the safety side. I guess you guys are only steroid, only immunosuppression for the DMD gene therapy-wise. Could you elaborate how that differentiate 003 versus the rest of crowd? Yeah. For those of you who do not know, we use steroids and steroids only. All the kids on Duchenne, they are always on a low-dose steroids. It is typically 0.75 mgs/ kg a day. That is every Duchenne child, because it has been shown to help and benefit the kids. At the time, any of the companies that are out there at the time, you boost up your steroid regimen, depending on the company that is doing it. Either us, we would go out 30 days with a higher steroid regimen. At 30 days, we start to taper. At 60 days, they are back down to the normal steroid dose for Duchenne. The other companies that are out there, they go out longer. They bump it up to 60 days, and then they try to start tapering down, from day 60 to day 90. Obviously, we have seen some of the cases that have made the news in the past with certain drugs that are on the market. That typically happens somewhere right around week five through eight. When you have in cases with the other therapies of GGT increases, ALT, AST, they tend to even stay longer than the 90 days of boosted steroids. Other companies also use sirolimus and eculizumab, and that is challenging for children, for the physicians, for the families. Why? You have to be on vaccines. You have to give the child antibiotics. You have to have a certain physician that can prescribe sirolimus. You have to have another physician that can prescribe eculizumab. You have to monitor for the sirolimus, you have to really monitor the kidney. You also have to look for gut issues, I think is contraindicated in children under 13 years of age. I think that is in the sirolimus label. It is because of, you can have gut necrosis, you can have kidney damage, and so you have to really monitor it. This puts a lot of pressure on the physicians because their biggest issue with treating Duchenne in general is their time, because they are very busy. They treat SMA, FSHD, all the other diseases that are out there. When they are spending a lot of time monitoring, it creates a bottleneck. If you can eliminate that bottleneck by just using steroids only, you can actually increase the output, meaning they can dose more patients because they are not focused on monitoring. I think that is where we come in, we are steroids only, outpatient. The kids basically get dosed, and a couple of hours later, they leave. They do not have to stay around the hospital. They can actually go home. I think that that is going to really matter if this drug ever makes it to the market. I believe it will. It is just a matter of time. I guess, I think almost everybody focus on the FDA meeting you guys are getting to the fourth quarter. Could you give us a little bit of color on what you guys have now, what is going to be your take into the FDA, and what are you going to ask about? Yeah. Be glad to. I will backtrack first, and then I will walk to where we are at right now. If we start our first meeting with the FDA was actually in late 2025, and we met with the FDA to talk about our phase III to get sort of a guidance approval, thumbs up on the phase III, which is our double-blind placebo control trial. That trial is ongoing. And we have met with them about the endpoints, making sure we got thought about the endpoints and ages and mutations, and all the good stuff. And so we got a thumbs up from the FDA to move forward with the Phase III. That was early 2026. We then met with the FDA in March, late March, early April of 2026, and that was really to establish a couple of things. One, to make sure that the FDA still thought Duchenne was a high unmet need. It is important because ours is a microdystrophin for gene therapy. There is a microdystrophin for gene therapy with the full approval. If the FDA would have said, "No, there is no high unmet need," it would have been challenging for us. But they said, "Yes, there is still a high unmet need in Duchenne." That is great. The second thing was to make sure that they thought our microdystrophin gene therapy was novel, and they acknowledged because of the capsid that we just talked about, because the construct with R16, R17 creating a novel protein, that it is a novel entity. Those two foundational questions were very important. Without them, it is hard to have a path going forward. We met with them, and we talked to them during that meeting about accelerated approval pathway and what they wanted to see, and they basically say, "Look, accelerated approval, at the end of the day, is a judgment call based off the totality of evidence that you create looking at a confirmation, sort of confirmatory that there is going to be a clinical benefit." And so we talked to them during that meeting about how we can think about analyzing the data. They gave us some ideas, and we ended. After that meeting, we knew that we needed to update the SAP plan. We told them we would update it. We updated that in May through July and submitted that to the FDA. And now we are starting to pull our data in. So where are we today? We're gathering all the natural history databases that we are going to pull. We're going to start analyzing our data compared to those natural history databases. We're going to put together the briefing book, request the meeting. The meeting should be held this year in Q4. Most likely late Q4, because it's typically 60 days in between meeting request and the meeting. We will, at that point, hold the meeting, wait for the meeting minutes, have the meeting minutes go to my board, and then I'm going to release all the data as well as the regulatory discussion to the street. I'll do so after I have the meeting minutes. That should be late this year. If it's not late this year, I won't drop it on you during Christmas. If it's somewhere right around then, it'll just be early January. To speak of the Phase III confirmatory study already getting studied. I remember you choose the time to rise at the 18 months. Yeah. Time to rise. As your primary endpoint. What's the rationale or discussion between FDA you guys picked that at the time? Yeah. There's a couple of endpoints you can choose from just to level set with everyone. You have NSAA, you have 10-meter run/walk, you have time to rise, you have four-stair climb, you have stride velocity. They're all different flavors, and many have been used. I think NSAA is a very good endpoint. It's a blunt instrument, though. You only have 1, 0, 1, 2, 3 or 0, 1, 2 to choose from. It's a good instrument, but time to rise has been used in other regulatory pathways. It is quote, unquote, "validated" for the FDA. I don't know exactly what validated means because none of the endpoints are really validated. They're just used more than the others. The FDA tolerates time to rise. Four-stair climb, 10-meter run/walk really haven't been used. One of the things that we like to mix and match, one of the things that the FDA says to us, and they did tell us this, I think they've told other sponsors. They worry about functional endpoints where there could be coaching, there could be bias, and sort of training. Any open label study that has a functional endpoint, that's what they worry about. What we try to do, we understand that. I think it's valid. What we try to do is augment functional endpoints like time to rise with other endpoints like Stride Velocity 95, and then show the correlation between the two endpoints. Stride Velocity 95, it's hard. There is no bias. You put little ankle bracelets on the children. They have to wear it four weeks in advance of their meeting with the provider, the clinician. They have to have a minimum of 50 hours to a maximum of 150 hours. The more hours you have, the less variability. Most of our kids have over 100 hours of time pre-meeting the physician. There's no human error. There's no stopwatch you have to worry about. If you can take that data and then compare it to time to rise or NSAA, four-stair climb, whatever endpoint you like, you can actually show that the two work well together. That's what we're trying to do. Take functional endpoints like time to rise, take stride velocity that has no intervention by human hands and coaching, and then sort of merge the two together. That's a long-winded way to say time to rise is primary, stride velocity is probably going to be our secondary. Oh, thanks, Bo. Let's shift the gear a little bit. The FA program is definitely your second pillar there. It's unique because you guys are using a dual- route delivery. Could you tell us a little bit more why you picked that kind of delivery method and what's the benefit from that? Yeah. Ultimately, you got to get to the cerebellum. The heart of the matter of FA is the cerebellum, Purkinje cells. FA is both the CNS and cardiac manifestation of the disease. If you're really going to make progress in disease, you got to get to the three areas. It's the heart, the spinal column, the cerebellum. By doing a very elegant way of dual route administration, which means you go to the cerebellum through IDN dosing. It's MRI guided using an enhancement agent. You can see real time your coverage of your dentate nucleus of the cerebellum. Cover the dentate nucleus, let the patient rest about an hour, then do the IV dosing. It's a one-two punch with the dosing all typically in the same day. You have to do it within 24 hours. You're able to cover the heart, the spinal column, the cerebellum. That way you can meet the patient wherever they are in the course of the disease, depending on the severity. If it's older patient, they're in their 40s, their mFARS are 80 and above, and they really can't move. You got to get to the heart, you got to get to the cerebellum. The spinal column's probably really in poor shape. You have a drug for them. You get to a 20-year-old, it could be a female patient, plus or minus a cardiomyopathy, but you need to get to the cerebellum. Maybe some DRGs are intact. You do the IDN dosing in the heart, you can get to that patient. Then like a six-year-old, the goal is ultimately to get to a six-year-old, or below. What is her disease going to look like? We have no idea. Is she going to have cardiomyopathy? We don't know. How severe of a disease she can have from a CNS? No idea. You dose her at doing dual route administration, and hopefully, you can stave off the disease or at least slow it down. I believe that this is an elegant way to treat anybody, get to all the patients long term, and meet them where they're at in their disease. It's a good way to keep the dose down. E12 is the low E12, and that's vg/kg is the IV dose. In the cerebellum, it's a total weight, and it's E9, very minuscule dose. I believe you got guided for initial data in the first quarter next year. Yeah. Could you tell us how the enrollment now and what's going to be the expectation for the data drop? Yeah. So, like I said earlier, I think you said it in your note, it's a one-two punch of Duchenne and FA because the data is going to be within a quarter of each other. In FA, we've dosed three patients. We had three screen outs due to patients being too severe in their heart. It's back on track now. Patient number four is scheduled this month. Patient number five is scheduled in October. We're hoping to have seven patients dosed by year-end. So early Q1, somewhere in Q1, we can have three patients of at least mFARS patient data for you at 90 days, and then about seven patients, hopefully seven, for safety. I think if that happens, then we're going to go meet with the FDA in first half of next year, talk about a registrational trial that we should have, quote unquote, "up and running" at the end of next year if everything goes. Up and running means we're working with the sites, trying to get the sites ready to dose. But realistically, I would like to be in a registrational study at the end of next year. That will be a double blind placebo control sham trial because I want to get this drug not only approved in the United States, but approved ex-U.S. and treat all the patients with Friedreich's ataxia. It's a massive market. Ex-U.S. is a lot bigger than the United States because of the family genetics. I see. To close, could you remind us your cash position? As of last quarter, it's $380 million, right around there. That takes us into first half of 2028. Okay. Thanks. Thanks, Bo. Thanks for coming. Thank you. Yeah. Thank you. Thank you very much.