Hi, good morning, everyone. My name is Farzin Haque, one of the biotech analysts at Jefferies. It's my pleasure to introduce Bo Cumbo, CEO of Solid Biosciences. This is a standard presentation, and we'll take some questions at the end. Welcome, Bo. Thank you. Thank you, Farzin. Thank you, Jefferies, for the invitation. Thank you for my friends for showing up at 7:30 in the morning for the presentation as well. All right. Please take time to look at the forward-looking statements. This is a very unique time in biotech, I'll be making a couple of forward-looking statements. Obviously, things could change over time, please take time to take a look at it. To talk a little bit about the clinical trials that we have ongoing today, we have a very robust pipeline, we're going to spend the majority of the time at the very top part and really focus in on three aspects of the company, which is the Duchenne 003 program, our Friedreich's ataxia program, it's called 212, and then our AAV platform, which is where SLB101 comes out of. We also have promoters that we're making. We have our next capsid that's coming along very nicely. It's in non-human primates this month. We have multiple other dual plasmids and manufacturing changes as well that we are in the process of partnering with across our industry. I'll spend the majority of my time today on our novel Duchenne gene therapy program called 003, and we've dosed over 50 patients now, and I'll get into the data. Sorry about the clicker. As everybody knows, we believe that Duchenne is a disease of muscle integrity and dysfunction, and we spend a lot of time not just looking at micro-dystrophin expression, but we also look at biomarkers of muscle integrity, such as CK, lactate dehydrogenase, titin, et cetera. We believe that these early signals of muscle integrity will confirm clinical benefit long term. That's why we take a hard look at it. There's three areas that we believe our program's novel. Actually, the FDA, we just held a meeting, we'll get into that at the end of the presentation. We just held a meeting with the FDA in which they even classified our program as novel. Really, there's three areas, and it's because our novel transgene. We are the only company that have a transgene that has the inclusion of this R16, R17 binding domain, which increases eNOS production, which is utilized for increased blood flow, decreased ischemia, decreased fibrosis, decreased inflammation, and we think it's extremely important to the children in Duchenne. We have a unique promoter called CK8 promoter that's very active in skeletal and cardiac muscle. The FDA even called out in our meeting the POLARIS-101, used to be called SLB101 capsid. The POLARIS-101 capsid has these RGD peptides inserted. We have about 60 per capsid, roughly, on each individual capsid, and they bind to integrin receptors in the skeletal and cardiac muscle. It has an increased binding capacity, so it gets in, transduces, ultimately express, and then it exits the body within about four days, 90% cleared out of the blood within four days. It's a very unique capsid. Now we'll get into some of the biomarker data. It really does not matter what biomarker you like, because they're all very consistent. We share all of them because some people like micro-dystrophin via Western blot, others like it mass spec. I prefer positive fibers, but they're all very uniform as you can see. We don't really stop there with just micro-dystrophins. We also look at positive fibers of beta-sarcoglycan. You all should take a look at the phenotype of a child that has limb-girdle 2E, limb-girdle disease. They have full length dystrophin. They have full length other sarcs, but they're missing this one sarc, sarcoglycan called beta sarc. In those patients, you end up with dilated cardiomyopathy. You have muscle weakness. It's very similar to Duchenne. As we start looking at these sarcoglycans and understanding the importance of human life from these actual full length proteins that make up the complex, we count them, we count the fibers. I think we're the only company that does count the fibers because these proteins are important for human life. We also look at nNOS activity. This is an activity enzyme at the sarcolemma. It's different than counting fibers or a Western blot. You're looking at the actual activity at the sarcolemma. We can see high levels of nNOS being restored, actively being restored, and it's the only program of its kind. We take a next step, and we go beyond just producing the protein. Does this have an impact on the body? We look at muscle integrity biomarkers, the chronic phase and the acute phase. It's anything from CK, lactate dehydrogenase, ALT, AST. We're the only company that actually looks at ALT, AST as a marker of muscle membrane integrity. Most companies think of it as a liver enzyme test. In Duchenne, they're sky high at baseline, 400, 500 at baseline. That's all caused by the skeletal muscle being broken down. What you want to see is decline over time. Many companies in gene therapy can't do that because they have that sort of In that acute phase of dosing, you see these spikes of liver enzymes, and our capsid SLB101 is liver de-targeting, and we can actually see a decline over time. It's important to look at this, but all these different biomarkers of acute and chronic phase lead up to another biomarker called embryonic myosin heavy chain that we put a lot of weight on. Embryonic myosin heavy chain is the one in the middle. We can have positive fibers I mean, on the left-hand side. You have both the combination of embryonic myosin heavy chain and positive fibers on the right-hand side. What's important is you want a reduction in embryonic myosin heavy chain. Why? Well, Duchenne is a complex disease of just basically regeneration and degeneration of the muscle tearing down. When the muscle tears down, our body tries to regenerate that muscle or heal that muscle, and they activate satellite cells. In the embryonic stages, this is what the little green dots are, and this is the muscle trying to repair itself. Ultimately, it wipes out the satellite cells and the pool of satellite cells. Then the kid, unfortunately, the child will end up with a fat fraction of roughly 80%, and they're off their feet. Here, what you want to see is you want to see a reduction. When you see a reduction, you actually know that the muscle fiber is not having to regenerate and repair itself. The satellite cell pool is intact and not being depleted. That's exactly what you see here with the 44% reduction. We take it a step further and look at cardiac care, and we look at ejection fraction. Many of these little boys end up with dilated cardiomyopathy over time. Some naysayers will say you don't have cardiomyopathy very early in life, and I will tell you don't wake up at 10 or 11 or 12 years old and just end up with ejection fraction sub 50% and cardiomyopathy. It actually happens over time. It's a slow drift. What you want to do is you want to monitor this. Many of the children that have Duchenne have spikes in troponin. Every couple of months, they'll have a spike in troponin. That's just their part of the normal disease, and that's these little micro tears that end up being fibrotic, and over time, you have ejection fraction decrease, and you end up with cardiomyopathy. We track all our little boys, many of which are in the normal range, somewhere right around ejection fraction of about 64, 65. We have 12 little boys that are on the right-hand side of the slide that are one standard deviation below normal. What we saw is every single one of those boys post-treatment, all 12 of 12 went right back into the normal range. This is a big finding. We actually believe we know why. We'll share that information more with you down the road. We're gathering more information. It's a novel find, and I think it's very important for Duchenne. When we look at liver, we know that this is critically important based on many factors that have happened out in the AAV gene therapy landscape. We look at ALT, AST, and GGT. We also look at bilirubin, obviously. What you can see here, and there are whisker bars on the GGT. What you can see here is decrease in ALT, AST. Look at the baselines, by the way, of ALT, AST. It'll be on the right-hand side of the Y-axis. You can actually see they're very, very high, and this is the skeletal muscle breaking down. Many companies, as I said, they can't monitor the decrease of ALT, AST because they have liver issues at the very beginning of dosing. We're able to monitor these children and take a look at it very closely. You can see reductions in ALT, AST. That's the skeletal muscle healing. GGT is flat. Bilirubin's flat as well. By the way, this is end of 2024, we've dosed actually 51 patients. One of them is placebo. It could be a placebo-controlled trial. 50 patients in the INSPIRE trial. All our levels look the same. We still have no drug-induced liver injury as of today, as I'm speaking right now. This is our new safety slide, this is end of 50. I think it's end of 50/51. One patient obviously is in the IMPACT study. We do not know if he's placebo or active drug. This is end of 50 with our INSPIRE trial and our safety profiles continuing to hold up. I do want to call out we had one little boy that had to be monitored in the hospital. He was treated with antibiotics, only antibiotics. He had a high white blood cell count, lab abnormality only. No clinical observations was reviewed in the hospital. Given one dose of two different antibiotics and was released. The kid's doing well. This is all our data that I just went over. This is basically all our positive fiber data, our expression data, our muscle integrity data, cardiac data. It's very consistent. It's the most comprehensive Duchenne program that I've seen looking at all the different biomarkers. This has given us a lot of confidence that as you enter this double-blind placebo-controlled trial, and it's an 18-month trial, we feel that these early biomarkers in the first 90 days really give us a lot of confidence that you're going to hit clinical benefit long term in the double-blind placebo-controlled trial. All right. Let's talk a little bit about SGT-212. This is our FA program. This is another very exciting program in a terrible disease. There's about 5,000 to 7,000 patients in the United States that have this disease. In Europe, because of the founder effect, it's actually larger. It's right around 20,000 to 25,000 patients. I think it's real important to understand that it's a disease that you have both CNS as well as cardiac manifestations of the disease. If you talk to the families of patients with FA, they'll tell you that the CNS aspect really is critically important. If you can't walk, see, speak, hear, read, swallow, cough, those portions of the disease, those manifestations of the disease, trump the cardiac output. We have a drug that is going to target both the cardiac as well as the CNS manifestations of the disease, and we do this in a very unique way, which I'll go into. I think it's critically important that you take a look at the Oh, sorry. Let me see. There we go. The mFARS. This is how we quantify the neurological function of mFARS, and it's a very good picture. Many of the programs actually focus in on the sort of green and sort of yellowish orange colors, and that's earlier. It'd be mild to moderate disease. We're very focused on the higher end. Both of our patients, our first two patients we dosed, were in the 80s, so very close. They have already lost their lower limb coordination. A lot of them have lost, both of our other boys had lost their upper limb coordination. You have to really focus in. It's extremely important to understand this because as you increase over time, your mFARS score goes up. Up is bad. Up is bad, down is good. Early in the disease, you can lose eight to six points per year. As you increase into your older years and get more severe, you'll increase your score somewhere between two and four points. In the very, very, very severe stage of life, which is where we're at, where we're focused in the red area, you can increase your mFARS score, which is a severity score. It will go up one to two points. What you never really see is you never see mFARS going down. You don't really see benefit. Once they've lost it, they lose it forever, and it's very challenging to get back. If we do start seeing benefit, this is going to be a game changer for this disease state for these families, and we're very hopeful that that happens over time. We've dosed two patients, and we'll have readouts later this year. We're doing something that's extremely unique. There's three areas that you really want to get to in Friedreich's ataxia. You want to get to, first and foremost, the heart of the matter is the dentate nucleus of the cerebellum. It's extremely challenging to push dose up via IV and get to that specific area. Even some of the neurotropic capsids have claimed that they can cross the blood-brain barrier. You're not going to go straight to the dentate nucleus. You're going to cover the entire brain. Really, you need to get to the cerebellum, more specifically, the dentate nucleus. You also need to get to the spinal column and the heart, and you need to be able to meet the patient where they are. By doing this dual route of administration, we're able to break the dose up and go very low dose, which has helped out with the safety profile, which I'll talk about in a second. We're in the total dose E9s for the dentate nucleus. That's total dose. It's not by weight. Then we're weight-based dose E12 for the IV dose to get to the heart and the spinal column. What you want to do is you want to create a drug where you can meet the patient wherever they are. By doing this, breaking this up wherever they are in their disease state, and by breaking this drug up and covering the spinal column, the heart, as well as the dentate nucleus, you can do that. If you have a 40-year-old that is completely severe, as I pictured on the last page, and they're really in the high 80s, and they only have this bulbar function left, and it's highly impaired, that's where covering the dentate nucleus can really help. If you have a 20-year-old that is still ambulatory, but has some cardiac dysfunction and they have another CNS manifestations, this is where the heart and the spinal column and the dentate nucleus will help. You have that six-year-old that just gets diagnosed, and you have no idea what her journey's going to be. This drug can help. It can cover the spinal column, the heart, and the dentate nucleus, and hopefully protect from mFARS increases over time or at least slow it down. It's the only drug of its kind like this, so it's very important for the community. This is the dentate nucleus. This is what we were trying to do the entire time. On the left-hand side, you can actually see the dentate nucleus in blue. What we show on the right-hand side, the very right-hand side, is actually the coverage of the drug. You can see it's extremely specific drug. It's not going all over the brain. It's very in a tight corridor. We were trying to cover 15%-20% of the dentate nucleus. We felt like if you covered 15%-20%, you would have a nice clinical benefit. We covered a lot more than 15%-20% in our first child. We covered even more in the second patient that we dosed. This procedure is quick. It only takes about 45 minutes for the actual procedure itself. The prep is about two hours. The procedure is very quick. They rest about an hour after this procedure. They get the IV dose of the drug. Eventually, this will be outpatient. To date, the safety profile has looked fantastic. Safety profile, we actually have no SAEs, no AEs in the second patient at all. He didn't even have a headache, nausea, vomiting, nothing. The first patient had a headache and was treated with Tylenol. Our third patient will be dosed this month. Unfortunately, we had our first third patient screen out because of low ejection fraction. Our next patient's going to be dosed. We're going to continue to dose non-ambulatory patients. Those are the most severe that I had on the chart. We're going to go down into age of ambulatory as well as ambulatory, non-ambulatory. We're mainly looking for safety as well as expression. Next year, if everything goes well with the FALCON trial, we plan on talking to the FDA and talking about how we can proceed into a registrational study. Currently, we have Ohio State, CHOP, and UCLA will be our three sites. Anticipated milestones, I'll talk a little bit about this. Let's start at the bottom though first, and let's start with CPVT. I just want to give you an update on CPVT first, and then we'll move up to FA, and then we'll talk about Duchenne at the last, and we'll finish it up. On CPVT, just to be very transparent, we're going a little slower on purpose. We have a lot on our plate with Duchenne and a lot on our plate with FA, two very important drugs to us. We're only 130 employees and limited cash. We're trying to walk slowly with CPVT. We do plan on dosing this year, but we're not in a hurry because a lot of our time is spending on FA and DMD. For FA, I just mentioned our third patient's going to be dosed this month, and then we have to wait 30 days, go to the Data Safety Monitoring Board, and then at that point we can start opening up our dosing. We don't have to wait the 30 days in between patients. Realistically, it ends up being about 60 days in between patients because you can't even start screening until after the Data Safety Monitoring Board meets. After we get through this third patient, we do expect dosing to increase over the course of this year. We're very excited. We'll meet with the FDA sometime next year and talk about registrational studies. For Duchenne, I'll spend the last four minutes of the time talking about Duchenne. We've had multiple meetings with the FDA. We've accomplished exactly what we wanted to accomplish when we wanted to accomplish it. Our first meeting with the FDA was around their double-blind placebo-controlled trial, and I'll tell you why we scheduled that meeting first. We wanted to make sure that they knew that we were going to give them a randomized control trial with a placebo arm because Accelerated Approval is going to be based off a judgment call, judgment call off the open-label study, we feel that if you have that randomized control trial underway, then they can actually lower the bar or at least keep the bar steady on evidence that you need in the open-label study. That's why we met with them. If you don't have that study ongoing, I got to think from a judgment call that the body of evidence needs to be increased in your trial. We met with the FDA first. We spent a lot of time with them on this. That trial is open. We've already dosed that patient. By the way, when we dosed our first patient, we sent the press release into the FDA to make sure that they knew that we had dosed that patient. That set up the second meeting. In the second meeting, we had four different parts of the discussion with the FDA. The first part was actually the most important. Is there an unmet need in Duchenne with a gene therapy, AAV gene therapy with a full approval on the market? Do you still feel that there's an unmet need with another gene therapy on the way? The answer was yes. The answer was yes, there is still an unmet need in Duchenne. I think that's critically important. Without that foundational step, you can't go to the next step. The next question that we asked them, which was the second most important question, is do you feel that the 003 program is novel compared to other programs that are on the market? If it's not novel, then if you have a me-too drug, a me-too gene therapy drug, then I don't see a path for you for Accelerated Approval. They said, "Yes. It's not only novel, but we give you two reasons why it's novel. It's novel because you have the R16, R17 binding domain, which we're recruiting for nNOS and producing a different protein. The second reason it's novel, and this is all in writing, is that the capsid, the SLB101 capsid is out there binding to integrin receptors and providing a broader distribution. That was a big win for us. The third question we asked, we were fishing. We've never provided functional data to the FDA. We don't have the functional data in-house. We've never run the functional data. We're going to do that over July and August, and I'll explain in a second, and we'll submit that to the FDA. We asked, "Hey, is our program, is our protein a surrogate marker for clinical benefit?" They clearly came back and said, "You've never shared any functional data, so it's too early to call that." We knew that going in. The last discussion was around the clinical trial design. It's clear, they made it clear to us, they made it clear to I think a lot of other companies out there that they're not really fond of open label studies with functional endpoints because they can have bias. They prefer a randomized control trial. In that same breath, they acknowledge that we have started a randomized control trial. They asked us a lot of questions about dosing, like when are we going to have it halfway full, or when are we going to have it a quarter full? They want the cadence of dosing, and we'll provide that to them in short time. I think that was a very important discussion. We know based on all the other feedback from all the other companies out there that they don't really care for open label studies. We sort of knew that going in, which is why we scheduled the double-blind placebo-controlled trial first. I think that that's going to give them confidence that if we show data when we run the data in July and August, and we provide that to them in the fall meeting, that they're going to be able to say the body of evidence is hopefully enough to get Accelerated Approval, and we have that randomized controlled trial underway and already dosing. This is our strategic game plan. I think it's a good game plan, and more to come. Just for the last couple seconds, because I know we're running out of time, we plan on submitting a revised stat plan to them this month based on the meeting that we just had with them. We're going to analyze the data in July and August. We're going to provide them all that data in the fall meeting. We're going to have that discussion around our data and hopefully get a pathway for accelerated approval. Then we'll share all that data with the community, the investor community, after we have the meeting with the FDA. With that, I'll just say thank you. Thank you, Bo. One quick clarification. Did FDA provide any feedback on how to analyze the functional data? Yeah, they did. The question was, did the FDA provide any feedback on how to analyze the data? They gave us ideas, yeah. A couple different ideas, actually. That's why we originally sent the stat plan in December. We're modifying the stat plan based off the meeting we had because they gave us a couple of different ideas of how to correlate data and also use another aspect of our data that I'm going to keep private for competitive reasons. We're modifying our stat plan. We're going to analyze the data July, August. We're going to schedule the meeting in the fall with the FDA, submit all that data, and have a discussion. Yes, they did have a discussion around how we should think about the data.