Welcome, everyone, for those in the room as well as listening on the webcast. Today at the Biopharma conference in Boston is Solid Biosciences. We recently launched coverage on them a few months ago. I have senior management from Solid here: Bo Cumbo, the CEO; Kevin Tan, CFO; and Cole Anderson, the Head of Investor Relations. Welcome, all of you. Thank you very, very much for coming. Let's just start with an overview question. If we could just introduce the company, the focus of the company, w hat are some of the key programs, and then we can get into detail on each of them. Yeah, thank you, Cole, and thank you, Citi, for the invitation. Solid Biosciences is a precision genetic medicine company. We primarily focus right now on gene therapy. Three main drugs that are going to be either, you know, that are in the clinic, INDs open, and we'll be dosing patients this year in all three of them, which will be DUCHENNE muscular dystrophy, Friedreich's ataxia, and CPVT. That's catecholaminergic polymorphic ventricular tachycardia. We also have another program that'll be coming up next year in dilated cardiomyopathy for our TNNT2. We spend a lot of time on next-generation delivery, whether it's capsids, promoters, or manufacturing process from a full to empty ratio. That's an overview of the company, about 110 employees based here in the Boston area. Excited to be here. Awesome. OK, obviously, it's a very topical summer for DUCHENNE, to say the least. Tell us about your program. Maybe just start by explaining, you know, what's different with your vector and your construct just to set the scene as far as, you know, differentiation versus what's available today. Yeah, we believe we have three different, you know, unique properties. One is the capsid itself, and we'll talk a little bit about that. Two is the construct, why it's different than others and what benefits it provides. Third is the manufacturing platform. We believe it's one of the best platforms out there from a full to empty ratio. From a transgene itself, the construct, we're the only construct of its kind that has this unique R16, R17 domain, provides recruitment for alpha-syntrophin and ultiimately nNOS. Once you have, it increases blood flow, decreases inflammation, oxidative stress. It also has effects in the heart as well, especially when you compare, when you add to increased levels of beta-sarcoglycan, as well as the domain of R16, R17 as well. We're hoping that all of this will translate into something meaningful in the lab. That's the first differentiation aspect of the program. Second is the capsid. It's a unique capsid. It's never been in humans before until this program, which is called SLB-101. What we've done is we've taken a parental capsid of AAV9. We've modified it. We've added RGD peptides in a certain variable region. I don't think we've ever disclosed. It targets multiple endocrine receptors on skeletal and cardiac muscle. We knew in preclinical studies that this led to, one, liver de-targeting. One, depending on the animal species, whether it was the mouse or the monkey, is the one to twofold differentiation of liver de-targeting. In cardiomyocytes, it was 20-fold greater than AAV9. Depending on whether it's the gastroc or the quad, 2x- 4x greater than AAV9, about 5x- 10x greater in the diaphragm. All of this should provide benefit to kids with DUCHENNE if it translates over. Looks like it is translating over. We're using the lowest dose in DUCHENNE, so 1 E14 with a full to empty ratio of -75% 80% full to empty capsids in a manufacturing process. Depending on how you quantify other companies' full to empty ratios and the total dose, you're talking over, it could be over a quadrillion different variants less than other companies. We think that that makes a difference from a safety standpoint. To be able to get to decent levels of expression, whether you're looking at mass spec or Western blot or, importantly, positive fibers, I think that that'll matter long- term. OK, you have shown some data already earlier in the year. Maybe you could walk through that because there was some evidence of a very strong expression for microdystrophin, as well as what looked like a good start on the safety side. Yeah, start with the safety since that's been front and center. The safety side, I feel very comfortable now. We've dosed 15 boys. Actually, we're continuing to dose kids. We announced 15. We've dosed most of the boys are ages five to 10 years of age. I think we have one boy that's outside that age group that we've dosed. Safety-wise, it looks very positive. We basically see nausea, vomiting, very transient thrombocytopenia. Ironically, in our press release, we released one Grade 1 liver enzyme increase. We debated on even putting that in the press release, but because of all the interesting things that are going on in gene therapy lately, we just put it in there for transparency. Safety-wise, we feel very comfortable. We've dosed 15 kids. We know pretty much what to expect now on every single patient, and they look great. We taper our steroids at day 32. I think that's important to know. We taper faster. If you don't know, all the kids are on steroids at a certain dose point, normally 0.75 mg per kg. That's daily, whether you're on a gene therapy or not. You dose up on gene therapy, and then you wait a certain time period, and you taper down. We taper at day 30. It's the fastest taper back down to normal baseline steroids of any company, and we think that that matters. The fact that we're able to do that, and we've been able to do that for every child, with the exception of that one child that has a Grade 1 liver enzyme increase, we've been able—93% have been able to taper from day 30 to day 60 and stay off enhanced steroids. That's great. From an expression standpoint, or really from everything else, we took a very holistic approach. We're going to continue to do that. We wanted to, you know, investors want confidence that your drug is doing something. We want confidence that we're to invest in a trial. We looked at multiple different levers. We looked at vector genome copies. Anything above 2 or 3, we feel is very positive. We were getting pretty high levels, even at 1 E14 dose. Everyone wants to talk about Western blot. Some people want to talk about mass spec. We released the data for both. However, I feel positive fibers are very important. How many fibers are positive in the child, depending on their muscle mass, because as you increase with age, you have less muscle. It's important to get to at least one out of every two positive fibers or have one out of every two positive fibers. Once you understand your fiber count, look at the entire dystrophin sarcoglycan complex and quantify it. Most companies just take a snapshot, but they don't really quantify it. We try to quantify that so we can understand the levels of beta-sarc or delta-sarcoglyca, because beta-sarcoglycan is very important in the heart. If you can get increased eta-sarcoglycan plus nNOS activity, which we show next, we are hopeful that it can lead to a benefit in the heart. Heart and pulmonary function, cardiac function, pulmonary function are the two main leading causes of death in. We spent a lot of time on that. Once we understood the complex was there, we wanted to understand muscle integrity. There are a couple of different ways you look at muscle integrity. There's the acute phase that can be highly variable. This would be CK, lactate dehydrogenase, ALT/AST. We can use ALT/ AST as muscle markers because we don't seem to have as big of an impact on the liver as what you would anticipate in gene therapy. Because of that, we can actually look at ALT/ AST, since the entire skeletal muscle is breaking down in these kids. We look and see if we can decline ALT/ AST over time. ALT/ AST, lactate dehydrogenase, CK would be your acute biomarkers. Then you can look at chronic biomarkers such as TITIN or troponin. TITIN ties back to sort of CK. You'll only see TITIN released in the blood or the urine when the muscle is truly decaying. Troponin, a lot of these young, young little boys, they have elevated troponin. They could be five years of age and have spikes of elevated troponin. They're transient in nature, but they're important to understand that it's the first signs of cardiac dysfunction at age four and five. By age 10, about 1/2 of the kids have underlying cause of cardiomyopathy. You can see a one-way shape or form cardiomyopathy. We track troponin, and we hope that we're decreasing their troponin levels over time so they're having less little events in their heart. We also track ejection fraction. Kids with, they're not normal. They're not in this range of normal kids' ejection fraction. Some are slightly below, depending on the age. They can be right at the cusp of normal, but a little bit below. Others can have a hyperdynamic range because their heart is under stress, so ejection fraction's higher than normal. What we're trying to do is take both ends of the spectrum and get these children into that normal range of ejection fraction over a longer period of time. We believe that if you can do that, if you can change troponin levels, change ejection fraction levels just to get them into this normal range for an extended period of time, that will have future benefit for these children. We looked at everything I just talked about to give us confidence that to invest in a clinical trial, that we would hit an endpoint. We believe that we're well underway. We're shooting for 20 patients by the year-end. I think we're ahead of schedule, but you never know. Right now we're ahead of schedule, but things can change. Right now I'm feeling pretty good about the whole program. OK, you listed a very long and detailed list of biomarkers and muscle physiology and enzymes and cardiology output. Of those, are we going to see that for all those 20 at the end of the year? Just give us a flavor for what the data set's going to look like and what we can expect. Yeah, you won't see it for 2020. We've dosed 15 boys right now. After you dose them, we wait 90 days before you get a biopsy, and then after the biopsy, it takes about six weeks to get all the data back. My expectation is we'll go into the FDA meeting, which we're going to schedule in very short order. We should have the FDA meeting at the end of the year in Q4. After that meeting, we'll wait for the meeting minutes. That'll be 30 days. Then we'll release all the data. What do we have going into the FDA meeting? We'll have about 10- 12 patients' worth of dystrophin data, and then we'll have about 15 or so, 14, 15 patients of safety data. Obviously, we'll gather additional safety data, and we can release that. I doubt we'll have much more data than what I just, you know, to be able to roll out to the public. Okay. What the FDA meeting, you've talked about it in the past, but it's getting closer. Yeah. What are the goals there? What are the, you know, what's going to happen in that meeting? What do you want to get out of that meeting? Yeah, we're going to, one, share all our data. We feel very good about the data that's already been disclosed. I don't have any additional data, if anyone's wondering. That's why you're going to see me at this conference and maybe one or two more. Then I will be MIA. You can feel confident that I don't have any dystrophin data right now, so additional dystrophin data. We'll disclose all that and talk about a path forward to the FDA. We're hopeful that the FDA is going to provide us a path forward for accelerated approval. We are going to be starting a registrational study at the end of the year, XUS. It will be a double-blind, placebo-controlled, multi-country, and multi-center trial. We're hopeful that, along with the data that we present and the data package that we're going to, you know, hopefully be able to give them next year, they can provide us a path for accelerated approval. That'll be the ultimate goal. Just give us some clarity on the accelerated approval process. Are there specific parameters that you're going to propose in addition to, obviously, you mentioned the ex-U.S. trial, which was an important statement to make to the FDA that that's underway or will be underway? What other sort of parameters would you hope to see in terms of what would be acceptable with the data set to submit? Yeah, we're sort of following REGENX path on that, which is 30- 40 patients of safety database, 10% mean expression for all the cohorts, and directional clinical benefit compared to natural history and using an external control. That's what we're going to propose. If they request additional patients, like if they say, we don't want 40, we want 50, that's not going to be a problem. We have, you know, in the range of in between 20 and 30 patients in the queue of screening right now. We've already dosed 15. We have 20+ patients, 25 or so, wanting to get into the trial in a screening process right now, whether it's antibodies or, you know, baseline criteria. The number, and we only have seven sites in the U.S. The number of patients trying to get into the trial is pretty dramatic. We're going to request, you know, 30-4 0 patients, 10% expression, directional clinical benefit. If the FDA requests additional patients, it's not going to be a problem. If they give you the pathway, what's the current thinking? Like when might you be able to launch? If they give us the pathway I just outlined, we would file for the BLA at the end of the next year. That would. End of 2026. End of 2026. Okay. Yeah, because we would have plenty of patients. Depends on how much follow-up they want. If the FDA requires additional patients that have 365 days of follow-up, that will change the dynamic. Right now, our best guess is based on the patients in the next year. Obviously, I got to get to the FDA meeting and get some clarity. Right. You mentioned the ages, five to 15. I think you said one. Five to 10. Sorry, five to 10 and one outside of the range. That's correct. What about the... We've dosed what we believe, and I'm not sure because I don't think anyone's really disclosed the ages, but we've dosed one young man under the age of 2. Okay. Is that correct that they're all still ambulatory, given the ages you said? That is correct. All our boys are ambulatory that we've been dosing. To propose a label, would it be for the ambulatory, or would it encompass everybody? We're only going for ambulatory at the time. This is all we're going to be dosing. We're going to be dosing ages 0 through less than 12. Status is ambulatory. Okay. Are there plans to go beyond that? There are, but we're making sure that we really understand the safety profile. We've dosed, as I said, 15 boys that have been announced. I would like us to get up to 30 patients and just really embrace the safety profile before we get into the older population, because that is a riskier population. They're older, sicker, heavier. Right now I feel pretty good about where we're sitting with the drug. I just don't want to put it at risk. Okay. What more can you say about the ex-U.S. study? I mean, one of the objectives is clear, but what else, any other details you want to convey? We haven't announced how many patients we'll be enrolling. The endpoints will be very specific, pointed endpoints like stride velocity or time to rise. We will be looking at everything else, obviously. 10 m run, walk, four stair climb, ejection fraction is going to play a role in this. Primary endpoints will be either a specific stride velocity or time to rise. Double-blind, placebo-controlled. We will be dosing kids that are younger through ages 3, 4, 5, and 6. However, pre-specified, and that's very important, pre-specified for clinical endpoints will be ages 7, 8, 9, 10, 11. Why? Because these are the kids that are a little bit more unhealthy. They're either plateauing or starting to decline on the endpoints. That way, we can tease apart the clinical benefit over time. It'll be an 18-month trial, not 12, because we believe you do need time in this type of disease, especially that late in life when there's been a lot of damage done. The argument would be that you're getting the functional data through that study. It wouldn't be the expectation that the FDA would want to see functional data out of your current study because that's not how it's set up, I assume. I mean, they're going to want to see directional clinical benefit compared to natural history as a comparator. You can look at a couple of different, you can break it down into different age groups because we are dosing different age groups that'll have different benefits at different times. We'll look at ejection fraction. I think safety, though, is also a very important discussion. We're steroids only. To date, our safety profile looks very clean because, you know, we see nausea, vomiting, thrombocytopenia, as I mentioned. We have that one Grade 1 liver enzyme that was transient in nature. I feel really good right now. I think safety will matter in the discussion. Let's talk about that a little bit more since there's been a lot of discussion on this point over the last few months. You're only steroids, and as you pointed out, the taper is relatively rapid, 30 days. What are some, I mean, some of the other approaches that are immunosuppressive, like Sirolimus and Soliris? How could those negatively impact patients if those are in a regimen versus not being in a regimen as you guys do? Yeah, I mean, there's a couple of different ways you could look at it. You could look at it from the burden of prescribing it, number one. I think you have a REMS with one of the drugs. I think it's Sirolimus. You have a REMS, or you have to have a different physician. You have a REMS. You have a lot more follow-up. When I talk to the physicians, it's while they like the triple immune suppression in one sense, it gives them comfort at the beginning. However, it doesn't give them comfort if they end up with an event. What do I mean? If you're on a triple immune suppression regimen and you end up with myocarditis, what does the physician do? They want tools, they want to treat, they want to help the patient. If you've used everything up front, it makes it challenging for them. They do think about that. The other thing is, you're lowering T cells for an extended period of time, and the kids are going back to school. What does that look like? Commercially, it makes it also challenging from a payer standpoint. Payers already have a hard time with some of these expensive drugs. To throw two additional drugs in a regimen, especially Medicaids or small plans, it makes it challenging. ex-U.S., it makes it very challenging, by the way. While we're sitting here talking about the United States., ex-U.S. in certain countries, Turkey's got over 2,000 patients, Spain, Portugal, Italy, you can't use triple immune suppression and try to get it reimbursed. The reimbursement authorities are very challenging to begin with. It depends on how you want to look at it. I think that that will matter long term if we can continue to stay steroid-free, I mean, steroid only. Right now, after 15 patients, I can see the safety profile playing out that way. I also want to ask you, as you talk to your physician network and your parent network, what are you hearing from the community as far as the desire and openness to additional approaches in gene therapy, given everything we've seen with the currently approved one? Yeah, I think every physician that I talk to believes in gene therapy. OK, so let's start there. They actually believe in gene therapy and see the results. Whether you're on a commercially available drug or you're going into trial, you know, we hear all the anecdotes. You guys don't want to hear about the anecdotes because that's exactly what they are, just anecdotes. We hear them, and we hear them a lot. Even on our kids, you know, some of the anecdotes about our, we have a boy that's doing ice skating for the first time. He's, you know, you typically don't ice skate if you're a DUCHENNE kid. These are the anecdotes. They believe in it. Now, we have seven sites in the United States. I'll talk about those seven, how they treat, because it's different than sites that don't have a clinical trial up and running. The seven sites that we have, they come to us first. They try to get into our trial. That's why we have like 25 or so, 25, 27 kids that are in the screening process right now. If they can't get into our trial, they try to get into REGENX trial or even Avidity or Wave or somebody. If they can't do that, they go on to commercial therapy. That's the seven or so sites that are our clinical trial sites. Then there's about 50 other sites that are active that are not doing clinical trials. They're taking a little bit more conservative approach, but they're still dosing a commercial drug. What they're doing, from what I hear, and this is just from what I hear, is that they are thinking longer term about the follow-up that they might need. They're just spacing out their dosing of patients a little bit more carefully so they don't get in a bind if they have to follow up a patient more often. I think that both of those work in our favor. It means that the patient pool will be bigger by the time we get to the market. I think also families are wanting to get into some of these different trials. That works in our favor as well. That's why we have so many patients that are lined up and ready to go. It's exciting, but we just got to keep doing the work. I assume your therapy would work with the exon skippers as well. I believe long term. I was on a panel one time, and they asked what I believe will look like long- term. I do believe it's going to be a combination therapy. I do believe that the payers will pay for it. That's long term. I think that they can be, they can work very well together. Okay, we could easily spend the entire time on, but I do want to make sure we cover some of your other programs. Friedreich's ataxia, obviously, you know, there's been a lot of progress there with the recently approved therapy, small molecule. Yours is, of course, different. Tell us about the approach there and the types of patients that you'd be targeting. Yeah, so we plan on targeting all, you know, all the patients, go all the way down the age group. Right now, it's greater than 18 and above for our first cohort, at least for our first cohort, and then in the first three to four patients. The reason is that's where the FDA wanted us to go. We want to get down into the younger age groups, at least down to age 12, relatively fast, hopefully in 2026, after we dose a couple of participants very safely, hopefully. We should be dosing our first patient in Q4. We have two sites that already have IRB approvals now, and we're working on the third. It's already pre-screening patients and getting them in the queue. We should be dosing in Q4. Be interested to see which site is the first site. We're excited. It'll be dual-route administration, the first one of its kind, where we're dosing both IV as well as direct into the dentate nucleus of the cerebellum, IDN. We believe that that's going to be the long-term benefit of this program. When we talk to all the families, they love the fact that there are programs that are trying to help the heart. If you can solve for or at least mitigate the issues around swallowing, speech, the ability, you know, all the CNS mobility issues, that's going to trump the heart. Quality of life always trumps the heart when we talk to the families. We did an event a couple of months ago. We had 300 families show up. We have people all around the world trying to get into the trial. I believe that if other companies that are in gene therapy that are focused on the heart, if they set this path for us for accelerated approval, more power to them because they're really going to help us out because we're going CNS as well as the heart. We're trying to get to, eventually get to the youngest kid that just gets diagnosed, that doesn't know what his or her path will be, whether they're going to end up with cardiomyopathy or a severe form of FA from a neurological standpoint. We should be able to dose them. We'll be the only program of its kind to treat all the manifestations of the disease by getting to the cerebellum, the Purkinje cells, getting to the DRG and the heart, I mean, the spinal column as well as the heart. I'm excited about the program. I think it's one of a kind. Can we go into a little bit more detail? Since it's, as you pointed out, it's two, it's one, it's one infusion, the IV, and then it's the injection directly into the cerebellum. How is it going to work with the patient? Is it going to be all happens at once, or that you check for safety with one, and then you do the next one? What are some of the details? That's a great question. It's relatively quick. The procedure is relatively quick. First, you do the IDN. It's an MRI-guided procedure, and it's infused with gadolinium. The surgeon will be able to see the coverage of the dentate nucleus in real- time. Based off preclinical models, we believe we can get to about 30% of the dentate nucleus that's going to provide long-term benefit. That procedure takes about an hour. At the end of the procedure, you literally have one of those small little Band-Aids in the back of your head where you inserted the catheter. That takes about an hour. You let the patient rest about an hour, then you start the IV. The IV is about an hour. All of it happens within the same day, the same drug, different amounts of drug depending on the route of administration, both very low. Because we're able to do the dual route administration, the dose is shockingly low. We haven't disclosed the dose. We will in short order, but it's very, very low. It's because the dual route administration lets you get the drug right to the areas you want without having to push too much gene therapy and potentially cause a tox issue one way or the other. I think it's a very elegant way to get the drug to the tissues and hopefully change the course of the disease. A couple of hours total procedure, IDN first, rest, IV second, and watch the patient for a couple of days, then I'm going to go. When are we going to get the first look at the results? Yeah, I'm hopeful that it'll be first half of 2026. We should dose our first patient this year. While the FDA mandates a minimum of 30 days in between dosing, which is standard for many gene therapies, most likely it will take about 45 days or so because it doesn't always line up to get a patient in, screen them, and get them in the surgical procedure. We will wait 90 days after that third patient. We'll batch our patients, and then we'll release it. I don't want to release one patient, one patient, one patient. I'd like to batch at least three. First half, if not, you know, right around the middle of the year. Are these patients that could be also on the SKYCLARYS drug? Yeah, we believe that. We're allowing SKYCLARYS. There's not really a standard of care for FA. SKYCLARYS is starting to become that standard of care. We do allow it in our clinical trial site, but there's really no drug that treats the underlying cause of the disease. It's outside of the ones that are in clinical trials or on the market. For commercially speaking, there's nothing out there that's true standard of care to treat an underlying cause of the disease. SKYCLARYS, they are, it's actively being used, though, yeah. Of course, I mean, it's a first in human, so it's primarily a safety and tolerability study to state the obvious. You know, mFARS is obviously one of the key measures. Is that something you would look at in an exploratory way? What would you want to, what would be a good outcome on that? It's too early to talk about a good outcome, especially when you're only looking at, let's call it 30, I mean, 90 days post-dose. We'll be looking at mFARS. We'll be looking at ejection fraction, you know, thickness of the heart. We'll be looking at other biological correlates, the whole picture. We'll take a very high-level look at everything. We'll present all the data that we find. That should be, you know, middle of next year. Okay. To briefly touch on some of the cardio programs, if I can say this right, catecholaminergic polymorphic ventricular tachycardia. You said it right. Yeah, it's a tough one. It's easier to say CPVT. We'll say CPVT from now on. What exactly is that, first of all? Just explain what the disease is and what's necessary there to have a therapeutic benefit? Yeah, basically, it's a calcium overload. The good news is we don't have to restructure the heart in this disease. It's really a signaling issue. Because of the mutations in the ryanodine channel, you have an excess calcium that creates an arrhythmogenic situation. Because of this, you don't, because of the way the nature of the disease, you don't have to coat the heart and soak up all the excess calcium. You just have to break the signal. Once you break the signal, then you should be able to reduce arrhythmias over time. That's what we've been able to prove in the mouse model. It's the only drug of its kind. CPVT, you know these kids. You just didn't know the disease. It gets misdiagnosed a lot, epilepsy, Dravet. They end up, a lot of kids die by misdiagnosed, or they're not diagnosed at all, and they're out doing an activity, whether it's basketball, rock climbing. There's a famous young man who died, but he got revived. He was rock climbing with his friends, got to the top, looked down, had a burst of adrenaline, went into arrhythmia, died, fell, he's paralyzed, he was revived. They identified that his younger brother, who had died when he was like eight or nine, had the same disease. He just got misdiagnosed. There's about 20,000 patients in the United States. It's a lot of patients. There's no drug out there. Beta-blockers, flecainide, ICD, like a, what's it called? ICD. ICD. Beta-blockers, flecainide, ICD, and really nothing else. This would be the first drug of its kind. You just got the IND cleared. Yeah. It's starting now. The study is starting. Q4 we're going to. Both FA and CPVT should be dosed in Q4. By the end of the year, we will have three different clinical trials going on in three different disease states. Technically, our fourth trial, which would be the registrational trial for DUCHENNE, starts in Q4. Four trials. Okay. Was there another program? TNNT2 is next. That's a dilated cardiomyopathy. That's an exciting program. No drug on the market for that one, no trials. Our preclinical data looks fantastic. We're excited about that one too. That'll be our fourth drug in the clinic. OK. Very good. All right, we'll have to leave it there. Thank you so much. We look forward to the updates from the meeting later in the year. Thank you very much. I appreciate your time. Sure.