Good afternoon. My name is Gena Wang. I'm SMID-cap biotech analyst at Barclays. Welcome to our Global Healthcare conference. It is my great pleasure to introduce our next presenting company, Solid Biosciences. With me, we have Bo Cumbo, President and Chief Executive Officer. Bo, maybe you start with, you know, a little bit overview of the companies, and we can dive into the questions. Great. Thank you. First of all, thank you, Gena, for the invitation to the conference, and thank you, Barclays. Bo Cumbo, CEO of Solid Biosciences. Solid is a precision genetic medicine company, focused mainly on neuromuscular and cardiomyopathies. We, Solid purchased a company called AavantiBio, closed on this in December 2nd of 2022, and I came from AavantiBio as the CEO of Avanti. Then, myself and my management team moved over into Solid Biosciences. We focus on Duchenne muscular dystrophy as our lead drug, followed by Friedreich's ataxia. Then we have four cardiomyopathies, either hypertrophic or diastolic cardiomyopathies or dilated cardiomyopathies. We also have a cardiac capsid library we work on for next-generation capsids, with a specific tropism for cardiac drugs as well as liver de-targeting. We have about 85-90 employees, and full PD/ AD teams, in-house with the capability of scale all the way up to 500 liters and for gene therapies right in our home office. That, that's a quick overview of the company. Our lead drug is with Duchenne. As I mentioned before, it's a next-generation Duchenne program, looking at with a new capsid, novel capsid that's never been put in humans before, a triple transfection manufacturing process, and then a construct that Solid used in its first-generation Duchenne program called 001. That program has been discontinued, but we kept the transgene for our second-generation program. Good. Thank you. Maybe I'll start with the new capsid. You've done quite some work to improve the tropism in both heart and the muscle. Maybe like, you know, can you elaborate what kind of modifications have you done and, you know, what kind of improvement you've seen in both muscle and heart? Yeah. We're doing a lot of work on novel capsids, and we're taking 2 different approaches, actually. We, we have one aspect of our capsid library that is using artificial intelligence, and then we're modifying a parental capsid which we've never disclosed on this side of the business. We're looking for tropism to the cardiac muscle, and we're going about it with RNA protein for cardiac positive selection and then DNA, you know, capsids for liver de-targeting. That part of the capsid library that we're working on has 3 different animal species, mouse, non-human primate, and pigs. We're already through our 1st round of non-human primates. We start our 2nd round of non-human primates and pigs in June-ish, like right around mid-year. Later on in the year, we do our third round of non-human primates and pigs. This part of our capsid library, final readout should be somewhere at the end of Q1 to early Q2 of 2024. It'll have a whole host of capsids that'll be next generation, like, as I said, multiple animal species, multiple rounds of animal species, and we'll use that for our own pipeline, our own cardiac pipeline, as well as non-dilutive financing. We've made sure that all the big biotech, big pharma know what we're doing with the cardiac capsids, and then we'll start looking for licensing opportunities in 2024. The capsid that we're working on for our Duchenne program, we took a very different approach because we wanted to quickly drive transduction and drive expression. When we're thinking about a new world where we're needing to bring a second drug into the market where you've already have potentially Sarepta or even Pfizer in that space, how do we create a next-generation program that can increase distribution, increase expression, that could be liver de-targeting? Also when you think about the speed of transduction that you're gonna need in a world where we're potentially redosing or looking at antibody-positive patients, how can we get to these patients? It really all starts with the speed of transduction. What we did is we've taken a whole host of capsids, and we've modified them one by one, really from a rational design approach of either point mutations or peptide insertions into the capsid. Then putting those capsids obviously into, a mouse and monkey and looking at the distribution. We're on the cardiac side, it's a very large library where we can take multiple libraries and flag them, on this side of the business, on the rational side of the capsid library, it's one capsid after another, inserting peptides, putting them in animal species, and looking for expression, distribution, and speed of transduction. That's where this SLB-101 capsid came out of. Mm-hmm. It came out of this side of the business, and that's what we're using for our second generation, Duchenne program. Okay. Going back to the cardio capsids to improve like why using pigs? Is that because also a good model for? It's a good model that the FDA likes for cardiac programs. I see. It, the pig heart, is a nice model when we're thinking about how we can take our programs into humans. Okay. going forward. Okay. All our programs that we have, we have four different cardiomyopathies we're working on. One we've disclosed, which is BAG3. We can talk a little bit about it. Mm-hmm. BAG3, we're very excited about that program. When we get into some of the larger species of animals, we'll probably look at not only non-human primate, but we'll look at specifically the heart in a pig model. I see. Good. Very helpful. Now going back to another also important improvement you made also the manufacturing, the triple transfection. Maybe, you know, the impact when you switch, like what is the impact in terms of yield and the scalability? Yeah. Give us a color. Solid Biosciences was using a HSV manufacturing platform in the past. We have moved away from that platform altogether, so none of our programs are on the HSV manufacturing system. Everything is now onto this triple transfection manufacturing platform. The new generation, the next generation Duchenne program, the FA program, and all our cardiomyopathies are on triple transfection manufacturing. We've taken the process that not only Solid worked on, but AavantiBio, and we've continued to make modifications on this process and try to create a very pure and clean product no matter what program you're working on. Just of note, you know, we're $97 million-$100 million dollar market cap company. We have a very decent sized PD/AD team. We also have what I think is critically important when you're thinking about manufacturing gene therapies. We have a regulatory, a CMC regulatory team, so it's outside the CMC strategy. I mean, regulatory strategy. It's a CMC experienced gene therapy regulatory team that sits in, embedded in our R&D PD/AD teams. Therefore, when we're thinking about modifications to process development, we have that team embedded and we're very thoughtful about any change that we make. But we've noticed that as we've been able to move from HSV to triple transfection, that, you know, CMC is the drug, and it really changed the way the drug is not only distributed but expressed. We're getting... If you don't change anything other than the manufacturing process, you're getting about 2 times different expression with our microdystrophin construct in the same animal species at the same dose. That's without capsid changes, without transgene changes or anything like that. We're very pleased that we're able to now work on a platform that's well-known. A lot of companies are using it, the FDA is familiar with it, you can scale up relatively easy. Inside Solid Biosciences, we have our own internal capabilities. We can go from 2 liter to 10 liter to 50 to 250 to 500 liter in our home office. We have the ability to go scale up to 500 liter. You, as you go into the CDMOs, then you can go to 1,000 or 2,000 liter relatively easy. Mm-hmm. That's one of the reasons we switched over, because it's very hard to scale. Mm-hmm. HSV, but not as much with a triple transfection. Will you be thinking in the future will be you were using CDMO process, or you wanted to do the internal? Yeah. We're not gonna get into CDMO business, so we're gonna keep that with them. It's just too expensive, too much of a burden, so. Mm-hmm. We have a vector core that's down in North Carolina. Mm-hmm. The vector core produces all our small scale material through mouse and some monkey studies. As the programs mature, we have the PD and AD teams, and that's the process development, analytical development teams that are embedded in-house in our headquarters. All of you guys feel free to come by the headquarters. We give tours because when you see the labs, we have roughly 50,000 sq ft of labs, full R&D, PD/ AD teams, and we give tours all the time so people can see the process. We scale from 2 liter all the way up to 500 liter in-house. Then as we needed to make GMP material for our first in-human studies, that's when we partner with a CDMO. We've publicly stated that Forge is currently our partner for our next generation Duchenne program. As you transfer from process development to the CDMO, we have a team that's called MS&T, Manufacturing Science and Technology team. These are PD experts that sit on the floor of our CDMOs. They're full-time employees of Solid that sit inside the contracted CDMO to make sure that the process development, the process that we have worked on, continues at the CDMO. We don't wanna just hand it off and pray, you know? We hand it off and watch. Mm-hmm. We have teams. We're in the middle of our GMP runs right now for first in human studies for our next generation Duchenne program. We have four people that are literally sitting in Ohio in a hotel room, and they go into the Forge every day and watch. You know, it's making sure that for any program, like our BAG3 program, it's very early stage. It's getting ready to go in non-human primates, but it's in a mouse. We have CMC regulatory people, that watch how we think about the materials right from the beginning. It goes to the vector core. Whereas we're getting to larger animals, it goes into our process development. It goes into our CDMOs. We have individuals that specialize in each one of those areas along the way. Highly focused on CMC. We, you know, A lot of us worked at Sarepta in the past. Myself, my chief financial officer, my chief operating officer, all came from Sarepta. We learned a great deal of manufacturing expertise from them and how do you think about the process from the very beginning of the program all the way through to human. That's what we built at Avanti. Now it's within Solid. Okay. Very helpful. Now going back, you know, switch gears on your programs, the next-gen DMD program. Maybe, since you have quite some modifications, you know, the mutation or the peptide insertion, and what is the highest dose you tested in non-human primates, and what kind of safety profile you see? Yeah. We have not disclosed the doses, but I will tell you that we believe that we've dosed two to four times higher than we'll dose in humans, in our non-human primates. We believe it's, you know, two to four times greater, dose in the non-human primates. We have taken down all the non-human primates. I don't have the data, so there's nothing to disclose 'cause I actually don't have it. We started the GLP toxicology studies in December. We finished in early March. Obviously, it's mid-March-ish now. We took down all the monkeys. What I can tell you is that all the animals from the time of dose to the time of takedown survived and were doing very well until takedown. Data, data pending, you know, we have to do the bioanalysis of all the data distribution, and tox work, and we'll have that data in the next couple months. We start working on the IND, writing the IND. Mm-hmm. Going back to your original question, we feel that we've dosed the non-human primates somewhere 2-4 times greater than what will be in humans. Okay. That will be the human equivalent dose, right? Yes. 2 to 4 times high. Okay. What about the potency assay? I know Sarepta had some. Yep. In the early development, and then I don't know if this is already. I think in the early, yeah. relatively established, everyone kind of follows. No, you have to have a potency assay. We've already contracted with the vendor to work on our potency assay. You really don't need it for your phase I, but it's nice to have for your phase I because- Mm-hmm. It really sets the stage for your registrational trials in the future. Mm-hmm. You can't really move into registrational trials without a potency assay. Mm. We understood that, and we started working on it immediately, once I, you know, really once we came in, and started working on this program, with in our GLP toxicology, we started working on our potency assay. We've signed with a third party that works on these potency assays. We should have it ready by phase I. Mm-hmm. that is our goal. Mm-hmm. If we don't, it's okay because we don't really need it for phase I. It's really nice to have as you transition from phase I through your registrational trials. I, you know, right now we're planning on having it for our phase I. Mm-hmm. Okay, good. It seems this a new capsid. You knw, any thoughts on existing neutralizing antibody when you go to the human percentage? Yeah. Population data. For this side of the capsid library, remember I told you there's two sides. Mm-hmm. One side we have not disclosed the parental capsid. On the other side, we have, which was AAV9, and we modified AAV9. Mm-hmm. That is where we found this capsid called SLB-101 that's going into SGT-003. Mm. We are working on antibody assays, but our assumption is going to be that it's directly overlapped with AAV9. Okay. Do you have similar like-? We have a third party that's doing an antibody assay for us. Mm-hmm. It's well underway. It will be ready by our phase I because you have to have it for screening purposes. Mm. Our assumption is right now that it's identical to AAV9 or close to it. Okay. Okay. Which means it will be like 30 to maybe 40%? Depend- Depends on the age. Depends on the age. Yeah. Depends on the study that you look at. Mm-hmm. You know, I've seen studies in the low 20s as high as the high 30s. Okay. You know. Okay. Great. Okay. Great. I think as you, as these children age, you do see higher sera. That makes sense. Now, you know, what are the additional steps you need to prepare in order to file IND in mid 2023? Yeah. We've guided to set what we say second half of- Mm. 23 for IND. Yeah. filings and approval and second half for dosing. Mm-hmm. You know, we're just looking at second half of the year. What are the next steps? Well, we've taken down the animals for the GLP toxicology. Obviously, we did the mouse studies prior. Mm-hmm. Taking down the animals for the GLP toxicology. We have to wait for the bioanalytical data. Mm-hmm. -to come in. Once we analyze it, we start writing the IND. GMP material is already underway. Mm-hmm. For the first in human studies, we have to make the material. We've already completed GMP 1. We're working on GMP 2. That material, you need stability. 3 months to stability to 6 months, we file the IND after it's written. You're looking at second half of the year IND, second half of the year, hopefully dosing. Mm-hmm. Okay, good. What learning you can get from? Because we're seeing already Sarepta moving very fast, and they have a Pfizer program and a previous solid program. Any thoughts on for the phase I trial design? Yeah. We do have big ambitions of how we can think about the future, of where we can go, what populations we can go in. Originally- Mm-hmm. We've got to focus in on safety. Mm-hmm. Our first, we're gonna dose roughly 8 to 10 patients on our phase I. That will focus on safety. Mm-hmm. microdystrophin expression. Mm-hmm. probably using a mass spectrometry. Mm-hmm. We'll look at dystrophin-positive fibers. Mm-hmm. That will be day 90. Really what we're looking at is how many fibers can we transduce and can we get to we believe what is a good threshold of microdystrophin expression, and safety. Safety is paramount. Mm. That's gonna be the whole focus of the phase I trial. At that point, then we'll evaluate, and then we'll pick the population we're going into. Going back to your question, what have we learned? 1, baseline characteristics... Mm-hmm. Selection need to be really scrutinized. If you go back to Solid's original program, which was SGT-001, you redosed children from ages 4 all the way up to 14, weights as low as 17 all the way up to 40 kg. Mm-hmm. We're not gonna do that. We're gonna really narrow down the age, make sure that we understand the mutations behind each one of the kids- Mm-hmm. Because every mutation acts a little different. Understand the baseline microdystrophin, as well as baseline characteristics on NSAA, six-minute walk test. All of this is gonna be as tight a range as possible. It might cause the patient enrollment to slow down. If you can, from a heterogeneity standpoint, tighten up your baseline characteristics, I really think that will lead you to a better educated idea of what you really have once the data rates out. Mm-hmm. That's what we're into. Okay. Will you do prophylactic Soliris? We haven't decided. I mean, obviously we're gonna use steroids. Mm-hmm. Yeah. We have not decided if we're gonna use another agent, so, Sirolimus or anything like that. More to come. One thing we know for sure, we wanna keep these kids safe and out of the hospital, the best we can because I believe that Duchenne has a long ways to go. I'm rooting for Sarepta's drug to get on the market because I think it's gonna help these kids. Mm-hmm. I also think it's gonna create a surrogate marker for clinical benefit from the FDA. Mm-hmm. That opens up a lot of possibilities of where we can take these programs in the future. Mm-hmm. What about Ultragenyx asset now? Yeah. I don't know their program. Mm. I came in in December. Mm. I did get to meet with Ultragenyx. We have a good relationship with Ultragenyx and collaboration, but really we don't share details on the status of the program. We do help each other out with IP- Mm-hmm. in filing IP and making sure that, you know, we know what broadly what's going on. It's their program. Okay. I don't know the details. Okay. complete independent. Yeah. We have a few minutes. Oh, sorry. Yeah. Yeah. I wanted to ask your cardio program. Maybe, you know, the rationale using, you know, the for the FA program of the rationale using CMV promoter. You know, CMV it was a promoter that was originally with the program. It looked very good from a transduction in the CNS. You know, we believe that We feel very comfortable that we have a lot of the data that we can modify the cardiac aspect of the disease. We also feel very strongly that you should not move a FA program forward without tackling both aspects of the disease, CNS, neuromuscular, and cardiac. Mm-hmm. The majority of patients have this CNS neuromuscular aspect of it. We wanted to understand if we can dose non-human primates, if we can dose dual route of dosing both IV and IT to increase not only expression but distribution without pushing up the dose because frataxin can be toxic if you push it up too out hard. We have completed a 40-plus non-human primate study. It was a 6-month study, and we did multiple doses, multiple routes of administration, IV only, IT only, dual route administration. We can see if we can elegantly distribute frataxin expression without pushing up the dose one way or the other. We've completed that, and we feel that we've now got a path forward so we can get into therapeutic ranges without getting into toxic levels. Now we've got to take it to the mouse model, the CNS mouse model aspect, tweak that, and see if we can modify that disease state. From our other cardiac programs, we have four different cardiac programs. Our lead one is BAG3. BAG3 codes for this Bcl-2-associated athanogene 3 protein. It is, if you have reduction in this BAG3 protein, you're getting cardiomyopathy, you're getting heart failure. Once you have the symptoms from BAG3, 25% mortality in year one, 50% mortality in year five, you are severely impacted and you're seeking treatment. 26,000 lives roughly in the United States. After you take all the commercial cuts, you're down to at least 10,000, 6,000-10,000 patients. It's a huge population seeking treatment. We're using RH74 with a cardiac-specific promoter. We've partnered with Dr. Adler out of UC California, San Diego. You know him from the Danon program at Rocket. His entire lab is working on this program for us, which we're going into non-human primates. Well, we've ordered the non-human primates. Everything's backordered. We're hopefully gonna get the non-human primates in the next couple of months, then we start our program there. We're very excited about the cardiac programs. We have four in the cardiac library, we believe in the next couple of years we're gonna see that pipeline, that part of the pipeline explode. The cardio program's in a little bit earlier stage development. Mm-hmm. At what point, like say 2023, like how much, you know, the animal data we will see? Well, if we can get the non-human primates. Mm-hmm. We go in non-human primates in our BAG3 program. Mm-hmm as soon as we get them. I almost slipped up and told you the other program, but in a hypertrophic, disease tape, cardiomyopathy... Mm-hmm We're looking at next round of just non-human primates at the end of this year to early next year. Mm-hmm. Our third cardiac program, it'll be early to mid 2024 for our non-human primate work. This year will be BAG3. Mm-hmm. Starting our second program at the end of the year. We have multiple, like I said, multiple cardiac capsids that will go through pigs and non-human primates this year. Mm-hmm. You'll have that data, and then we'll be first in human and Duchenne. FA is, we just have to tweak the mouse models, and we're moving everything to a triple transfection manufacturing process, and then hopefully on to IND study. Okay, good. Well, thank you very much. Thank you. This, I will look for, quite some update later this year. Yeah. Thank you. Thank you very much for the invitation. Appreciate it. Okay. Thank you. Thank you. Thank you, everyone.