All right. Well, thanks everybody. Good afternoon. It's day one of the Cantor Fitzgerald Global Healthcare Conference, ending the day with one of my top picks, Solid Biosciences. Joining me on stage is Bo Cumbo, the President and CEO. Thanks so much for being here, Bo. Yeah. Thank you, Kristen. Thank you, Cantor Fitzgerald. Yeah. Of course. Maybe just to kick things off, do you mind providing us with a very high-level overview? Solid Biosciences is a precision genetic medicine company, but we are primarily focused on gene therapies right now. Our two main products are with Duchenne muscular dystrophy and Friedreich's ataxia. We have other cardiac programs. They are going a little slower because we are putting all our money and all our emphasis on the two main programs, which is Duchenne and FA. We also have a very unique platform, where we build different delivery tools such as capsids and dual plasmids, promoters, and we leverage those capsids for our programs, but we also give them out to academic labs and building a pretty big profile there on delivery for gene therapy for next generation gene therapies. Before we talk about some of your individual candidates, I think it is important to set the stage about the DMD landscape first. We have had a gene therapy on the market for three years now, a launch that has come with a few unfortunate setbacks. Big picture, what has this launch shown you in terms of patient interest and the ability for a gene therapy to succeed here? We have been very fortunate. Obviously, we have dosed 53 patients in our INSPIRE trial. The trial is pretty much full. It has been full for a while. What the sort of trend was that we increased dosing in the trial pretty dramatically over the course of the last year and a half, and we were able to fill that trial very quickly. There was a lot of demand, and I cannot remember exactly how many patients were sort of hoping to get in the trial, but it was well over 100 when we basically shut it down. The demand was high. I think a lot of families want second generation gene therapies, especially ones with unique capsids that can provide better distribution. Also, maybe a little bit of a safer profile to date, and so we are very excited about it. The demand was high. I think there is a lot of demand for the drug. There are a lot of people that want the drug. Unfortunately, the trial is relatively closed in the United States. We are going to dose about three to four more little boys at the very end of this year using the CMC commercial material. That's the only children that we're going to dose going forward in the INSPIRE trial. The reason we're doing it that way is so we have some bridging data from our phase I/II to our phase III using the commercial material, and that'll be three to four patients worth of dosing that we'll do at the end of the year. That's a long-winded way of saying the demand was intense. We believe that it's going to be intense for our phase III trial once we get Europe up and running, as well as the sites in the U.S. And it shows you what it's going to look like if we can get this drug to the patients commercially. I think that there's going to be a very big uptake relatively rapidly. Okay. For DMD gene therapy, we've seen situations where biomarker data nicely translates to clinical outcomes, and then situations where this hasn't happened. Do you think there are particular biomarkers at this stage that are most predictive of clinical outcomes we should be paying attention to? Yeah. No, it's a great question. Look, let's take a step back. three years ago, we were a $38 million market cap company, and we were really having to do a lot of work, understand where we could put our money for our programs. So one of the things we did as a company is we didn't take a look at one biomarker or biological correlate. We looked at 10 to 12, and we feel that it was extremely important to us at the time. Now it's important for you as investors, and it's important to families and physicians to look at what we believe is the most comprehensive data set that's been put together in Duchenne, period. So we don't look at one biomarker or one biological correlate. We look at a host of them. I call it a waterfall. Some of my other colleagues internally call it a bridge. But realistically, it starts when the needle goes in the arm. You look at the VGs per nucleus, then you go Western blot, mass spec, positive fibers, the sarcoglycan complex coming together. Then you take a look at nNOS production, as well as the next step, which is your biological, your muscle integrity, CK, ALT, AST. ALT, AST, you think it's a liver biomarker. In Duchenne, at baseline, they're somewhere between 300 and 500. It's the entire skeletal muscle breaking down in these kids. Then you take a step and after the acute phase, you look at the chronic phase, which is titin. You see titin that's broken down in urine and blood. That's when the muscle's completely degenerating. You look at troponin, the heart. Every one of these kids are having little spikes in troponin. You look at troponin over time. Then you get into muscle integrity, muscle maturation, the satellite stem cells. Duchenne, this is a degeneration, regeneration process that repeats itself over and over. After you follow this waterfall down, you will get embryonic myosin heavy chain. Can you halt this sort of stem cell trying to repair the muscle or regenerate the muscle? When you see embryonic myosin heavy chain decline up to 40%, that gives you hope that the muscles are getting stronger, they are staying intact. That gives me belief that eventually you are going to see clinical benefit. You have too many biological correlates all pointing in the same direction, telling you a little bit of a story all the way down the pipeline. I do not look at one, I look at all of them. I think they all tell slightly a different story. In totality, it tells you the muscles are getting stronger. There is going to be clinical benefit. It is just a matter of time and how you design the trial, and who you put in the trial, and the endpoints you get. Thank you. Based on your math, what percent of the prevalent pool could still be eligible for gene therapy, and how is this number changing as incidence, of course, occurs over time? Yeah. Let us break it out because I think it is very different. The total number, my guess is 80%, but realistically, you have to break out ambulatory versus non-ambulatory. Right. We're really primarily focused right now on ambulatory kids, and when I say ambulatory, I also mean pre-ambulatory because ages zero, one, two, three. So it's pre-ambulatory to ambulatory. That gets you up to about age 12. Realistically, from age 12 on, of the children that are living, I would say the majority of them are ready for gene therapy. We're not going after that right now. We will down the road. We're very fortunate to be in the safety position that we're in. We don't have any drug-induced liver injury. We don't have any myocarditis. We don't have any TMAs. We only use increased steroids for 30-day stent. I want to keep the label as clean as possible. So we'll come back to the non-ambulatory boys. For the ambulatory boys, after you take in antibodies and you take into consideration exclusion criteria for different mutations, my guess is roughly 50% of the children are still eligible for our drug. That's somewhere in the 2,000 range to 2,500 to 3,000. Somewhere in that range is probably about the right number. Okay. Let's shift gears and talk about SGT-003 now. Can you first please touch on some of the work that Solid Biosciences conducted to understand which components of the central rod domain of the dystrophin protein are most critical to restore for a microdystrophin construct? Yeah. A lot of the work was done by Dr. Jeffrey Chamberlain. Yeah. He was the original that did all the work. Matter of fact, he really created all the microdystrophin constructs, and he created them in order. He started work on the earliest ones, which were the ones that Sarepta used. You can look at Pfizer's approach and REGENXBIO. The last construct he ever made was this construct that we're using right now. It was critically important that he kept tweaking. He tweaked a couple different things. Obviously, not only the domains, but also the hinges. Why are hinges important? You're taking a very long protein- Yeah and you're shrinking it down. Hinges are critically important because depending on the hinge that you have, it can be the rigidity in the protein. When you shrink this protein down, you want to make sure it's as flexible as possible, and there's studies out there that talk about this. We make sure that we have just hinge one and hinge four. Then you get into what repeat domains are important, and he landed on R16, R17. Why R16, R17? When you have R16 and R17, you can actually recruit for some other proteins. One's called alpha-1-syntrophin. When you have alpha-1-syntrophin, you can recruit for eNOS. eNOS, the neuronal nitric oxide synthase, you can actually see that that increases blood flow, it decreases fibrosis, it decreases inflammation. There are boys that have Duchenne or have Becker that have R16, R17 in their domain. Actually, these individuals have been shown to walk longer than other little boys that don't have it. Dr. Chamberlain really thought that this domain was very important. We're also learning more about R16, R17, alpha-1-syntrophin, and what other proteins they recruit for, like the cavins, the cavin-4. We're doing work right now to try to understand this because this can have an impact on the heart for calcium channel handling and other important measures. We're just now working with researchers on this. It's actually quite important because we're actually learning more and more and more about these proteins. I think this is one of the reasons that this construct, and a lot of the researchers believe that this construct is the best one. It was the last one that Dr. Chamberlain worked on. Okay, then talking about the capsid, what is the expectation of what greater biodistribution to the muscles and heart could lead to, just on efficacy first? Well, we believe microdystrophin matters to clinical benefit. Yeah. If you can actually get to more muscle and a broader distribution, we believe that that ultimately is going to provide clinical benefit for these kids. We saw it in preclinical models. I actually think it is playing out. Obviously, we are not taking biopsies and doing all the work that we did. Right. Yeah. in children that we did in the mice or the monkeys. What did you see in the mouse and the monkey? We saw much greater biodistribution. Depending on the muscle group, it could be anywhere from three to five to five to 10 times greater. The diaphragm was significantly greater than AAV9. We did most of our work comparative AAV9. We think that this is playing out in the child. We give the lowest dose. So we are 1E14. Sarepta's ELEVIDYS is 1.33E14. REGENXBIO is 2E14. Yet we are getting just as good of expression, if not greater, than most of the studies that have been shown. We think that this matters, that this is because we are getting to the muscle, we are getting broader muscle uptake, and it all comes back to this capsid. This capsid, we intentionally designed around with these RGD proteins, and these RGD proteins are for integrin receptors, mainly two integrin receptors in skeletal and cardiac muscle. That is what we inserted. There are about 60 of these RGD proteins, peptides per capsid, and we call it binding capacity. It is a made-up term, but realistically, what is it? It just binds, transduces, and expresses to the muscle, to the integrin receptor faster than any other capsid, broader distribution than any other capsid, and then it clears very quickly, and that is very unique as well. We actually did not even know this until within the last year. We did not do the work on this in the mice or the monkeys. But in our human subjects, we looked at clearance in the whole blood. By day 4, 90% was cleared. I think this plays a major role in safety. Yeah. This is why we have not seen, we believe, some of the TMA or aHUS cases, because by the time your complement system is really activated and looking for something to clear, it is out of the blood. This is all to the unique design of the capsid. The heart is a whole another thing. The heart, compared to AAV9, when we looked at human cardiomyocytes, we were seeing expression like 19, 20 times greater. We believe that this capsid is. We saw it in the mouse. We saw expression at day four in the mouse, 75% in the heart at day four. It is really, really unique. I think it is all playing a big role in why we are seeing the expression that we are seeing, why we are seeing the safety that we are seeing. It all comes back to this novel capsid, this next generation capsid called AAV-SLB101. We call it POLARIS-101 now. Okay. So what can you tell us about the data set the company's reviewing right now? What is the plan when you meet with the agency later this year to hope to align on? Yeah. So the goal right now, just to give you some background, I will go all the way back to December, so that way it leads you up to now what we are going to do in the next Sure couple of months. In December, we met with the FDA. We talked about our phase III clinical trial design. We got that sort of approved. We also submitted our SAP for how we were going to analyze the phase I, the INSPIRE trial, and we submitted that in December. In March, April, we met with the FDA again. We talked to them about Accelerated Approval. We made sure that they thought our product was novel. We made sure that it high unmet need in Duchenne. We talked about next steps, and they wanted to see clinical data. They gave us some ideas at that meeting, how to think about the data, how to analyze the data. So we had to update the SAP based on the one that we submitted in December. We needed to modify that SAP. We submitted that in July, very, very late July of this year, just a couple of months ago, two months ago. That then started the time clock of, okay, well, now we can start taking a look and analyzing our data. It starts with making sure we can get all of the natural history data in. We have multiple different data sets that we want to utilize. That was all part of sort of like how we think about the SAP plan. We are gathering that data. We are also now going to start analyzing our data, matching it to external controls, putting that together, looking at Stride Velocity 95th Centile, Time to Rise, four-stair climb, 10-meter walk/run test. We will also look at cardiac data, but that is not going to be utilized for functional data. That is going to be utilized for safety data. The goal is we get that data together, we start making this briefing book. Soon, we request the FDA meeting. Once we request the FDA meeting, it should take about 60 days before we are granted a date. That date should be somewhere in Q4, probably late Q4, based off the timing, if you could add the 60 days, since we are already in September. We are going to wait for the meeting minutes. I am going to have the meeting with the FDA. The meeting minutes sometimes can be sanitized from the meeting, so you want to make sure that you actually have the sanitized version before I come out to the street. Then I will tell you and give you all the data. That should be either late this year or very early next year, like right around JPMorgan timeframe. Basically, December 15, we cut everything off in December 15. We are not going to try to surprise the street with dosing any patient or giving you guys data and making you guys work over the holidays. So realistically, if you do not see it by December 15, it will be very early January. Okay. In addition to the data, you will tell us what the strategy is, whether you pursue Accelerated Approval Program at that time as well? Yeah. Okay. We are going to ask for. Right a path. Yeah. Whether they give it to us or not is up to- It will be a regulatory and a clinical data update- Yeah essentially in one. Okay. You are also going to have FA data in very short order after that. It is going to be sort of a one, two, three punch, clinical data on Duchenne, regulatory data on Duchenne, mFARS, and safety data on FA, and you will probably all have that all within a two, three-month period of time. Okay. We love nothing more than being kept on our toes for nonstop announcements, so we will be ready for that. I did want to make sure we could cover some time on your FA program today, SGT-212, excuse me. For this program, you are using a dual route of administration to target both the neurological aspects and the cardiology ones of this disorder. How does this procedure relate to some of the other surgeries investors might be more familiar with in the gene therapy space? I am thinking like the Huntington's space in terms of complexity, time- Yeah et cetera. This is a very different, very streamlined surgical approach. The actual surgery itself only takes about an hour, 45 minutes to an hour. The prep is about two hours prior. The surgery is in and out. It will end up being outpatient. Total time from the patient actually coming into the surgical center, getting ready, entering then the MRI, and then actually doing the surgery is four hours soup to nuts, and that is from time they come in to the time they are just resting. Yeah. It is a very different procedure than what people are used to in some of the other spaces. Procedure is done very quickly. It is done relatively easily. It does not take a lot of time. The actual surgery itself, somewhere between 45 minutes and an hour. It is just the prep is two hours, and then the resting is one. Okay. In the setting of FA in particular, how much follow-up do you think is required across key populations you are studying to understand potential efficacy assessments, especially because it is both cardiac and neurologically driven? Which endpoints might be more obvious for you, given the direct involvement of the dentate nucleus? Yeah. We are sitting in a really good spot. We are going to be able to track both cardiac manifestations, the heart, the left ventricular mass, as well as ejection fraction. We can look at other aspects of this, but we are going to be focused on mFARS really. mFARS or modified mFARS will be our endpoints. I think it is really interesting to look at, to think about the natural history of the disease and understand that mFARS does not decrease. It just continually marches up and to the right, and that is not a good thing. Depending on how many points you actually lose, a year is where you start. If your baseline as a mFARS is like 20 or 30, you have the potential to lose four or five points, meaning getting worse, of increase of mFARS in a year. If you start in the 40s, you might lose two to three points. You start in the 60s, you might lose one to two points. You start in the 80s, you might lose 0.5 to one point, depending on, and all of that is negative. I think the takeaway there is you never decline. You are always going up. You are always getting worse. There is no stability in mFARS. You just keep marching, unfortunately, to a very bad place. This is where our data comes in. If we start seeing declines in our patients, we have dosed three patients to date, all very safely, by the way. Our third patient was dosed early August, so we are over that 30-day period, so I feel comfortable saying she was safe, along with the first two. We have no SAEs. Right. If we start seeing a decline in mFARS or stability in mFARS, this is a huge win. Let me put it in perspective. When our first two patients were dosed, they were in the 80s. What does 80s mFARS mean? Realistically, when you talk to the KOLs, there's not a lot of data out there for 80s because mFARS, the worst of the worst is 93. But an 80 is just as bad as a 90 because it's very hard to actually predict the severity. They're strapped in. They've lost the ability, obviously, to walk many years ago. They can't really use their hands. They can't sit upright. The ability to speak is limited at best. They can barely swallow. They're very thin. Most of the time, they have lost the ability to control their pupils, so they can't read. It's not like reading like myself, I have to wear glasses. It's that you can't stabilize your eyes to see the words. If we start seeing a decline of even a half a point, one point, you have brought that patient back multiple years in the disease progression. This is where we're going to take a look at our data. If you have a two point, three-point decline in these patients, you can really create a double-blind placebo-controlled trial with very limited number of patients and get a P value. I think it's going to take us somewhere between seven and 10 patients, somewhere within a range of mFARS of 40 to 80, so we can understand what our score really is of decline after maybe three, six months of time. I do think you probably need more than three months, somewhere between six months, just to see what that decline is. That's going to help you build a very robust phase III. Our goal is to dose seven patients by the end of this year. That means that we can go to the FDA somewhere in the first half of next year and start planning a registrational trial to kick off in the second half of next year. If we have declines in mFARS, even of a point or two, it is a game changer for this community because mFARS never declines. Then we can power this study appropriately, and we, I think, will have a program that the majority of patients for Friedreich's ataxia, not only in the U.S., but ex-U.S., will gravitate to, and it could be a game changer for them. It's the only drug out there that can really change the CNS and cardiac manifestations of the disease. Of course, we're going to check ejection fraction. Of course, we're going to look at left ventricular mass, and that's going to provide benefit to them as well. Also, the last part, I'm sorry I'm long-winded on this. No, it's okay. I think it's very important that we do this placebo-controlled sham trial. I've had conversations with Farah about it, because when you look at FA, you should not just look at the patients in the U.S., you should look at the patients in Europe. There's 15,000 to 20,000 patients in Europe. FA, if we look at the model, I don't know what your model says, I know what ours says. It's about 40%-50% of our total revenue can come from Europe. That's even with a reduction in price that we typically have in gene therapies. Europe is massive. That means you have to give reimbursement in Europe because the process is very different. You deal with the HTAs. You need a P value and a double-blind placebo-controlled trial. We're going to do that trial, and we're going to try to bring this drug to everybody in the U.S. as well as Europe and globally. But really, Europe is it. I'm very excited about this program, very excited about Duchenne. I think we're one of the only companies that could have two phase IIIs going on next year, both from a Duchenne standpoint and in FA. This makes us one of the most powerful, little dynamic, little gene therapy companies that's out there. We've come a long way in the last three years, and this year is sort of like that turning. Next year could be explosive for us as a company. Yeah. Bo, for the data disclosure next year, you would present us data on some patients prior to meeting with the FDA? Are we talking about FA? FA, yes. Sorry. Yeah. The game plan is you guys are going to probably get data. I wouldn't guarantee Q1, but it's going to be close. Okay. But this will be before you have that meeting with the FDA to say, "Hey- Yeah let's talk about a registrational trial. Yeah. Okay. Yeah. Okay. Are we going to see biomarker data, functional endpoints? You know what? Look, Duchenne and FA are just so- Yeah different. Right. You don't really. Like Duchenne, we want to talk about expression. In FA, I don't know if you really need it because you can look at mFARS, and you can look at- Sure sort of just change. I don't know if we'll look at how many biological correlate data we'll look at for FA, but we're definitely going to have mFARS. We'll have left ventricular mass index. We'll have ejection fraction. We'll have some biopsy data. It'll be limited, but we'll have some. We'll try to present all this. Okay. Any closing comments you'd like to leave us with? I'm very excited about the future. This company's come a long way. I'm really excited for the kids, not only in Duchenne, but for FA. I think we're developing some of the best in class and first in class type of drugs, best in class drugs for Duchenne and FA. It's exciting for the future for the patients, exciting for the future for the company, hopefully for investors. We're making a lot of progress. We're putting all our money, all our emphasis on these two programs. Last but not least, don't underestimate the power of the platform. Yeah. You're going to see, I believe, that the majority of companies and academic labs in the next three to five years are going to use our delivery tools and AAV Solid inside of the constructs. That's going to provide, while all the investors are focused on this sort of quick one-two punch of Duchenne and FA, the long tail is going to happen of all the royalties that are going to be generated off the platform. It's a really cool little company. Thank you so much, Bo. We're rooting for you. Thank you. Yeah. Thank you, Kristen. Thank you very much. Thank you.