Solid Biosciences Inc. (SLDB) Earnings Call Transcript & Summary

Good afternoon. My name is Gena Wang. I'm SMID cap biotech analyst at the Barclays. So 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. And Bo, maybe you start with a little bit overview of the company, 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. I'm Bo Cumbo, CEO of Solid Biosciences. Solid is a precision genetic medicine company, focused mainly on neuromuscular and cardiomyopathies. Solid purchased a company called AavantiBio, closed on this on December 2, 2022. I came from AavantiBio as the CEO of AavantiBio 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. And then we have 4 cardiomyopathies, either hypertrophic or diastolic cardiomyopathies -- 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 detargeting. We have about 85 to 90 employees, full PD/AD teams in-house with the capability of scale all the way up to 500 liters for gene therapies right in our home office. But 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 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. So maybe I will start with the new caps. You've done quite some work to improve the tropism in both heart and the muscle. So maybe like can you elaborate what kind of modifications have you done? And what kind of improvement you've seen in both muscle and heart?

Yes. So we're doing a lot of work on novel capsids. And we're taking 2 different approaches, actually. 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. And we're looking for tropism to the cardiac muscle. We're going about it with RNA protein for cardiac positive selection. And then DNA, capsids for liver detargeting. That part of the capsid library that we're working on has 3 different animal species, mouse, nonhuman primate and pigs. And we're already through our first round of nonhuman primates. We start our second round of nonhuman primates and pigs in June-ish, like right around midyear. And then later on in the year, we do our third round of nonhuman primates and pigs. This part of our capsid library final readout should be somewhere at the end of Q1 to early Q2 of '24. And it will have a whole host of capsids that will be next-generation 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 nondilutive 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. Now 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. So when we're thinking about the 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 detargeting, but also when you think about the speed of transduction that you're going to 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. And 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. And then putting those capsids obviously into mouse and monkey and looking at the distribution. So it is a -- where 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. And that's where this SLB101 capsid came out of. So 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 the...

It's a good model that the FDA likes for cardiac programs. So the pig heart is a nice model when we're thinking about how we can take our programs into humans going forward. So all our programs that we have. We have 4 different cardiomyopathies we're working on. One we've disclosed, which is BAG3, we can talk a little bit about it. BAG3, we're very excited about that program. But when we get into some of the larger species of animals, we'll probably look at not only nonhuman primate, but we look at specifically the heart in a pig model.

I see. Good. Very helpful. And then okay, now going back to another also important improvement you made also the manufacturing, the triple transfection. So maybe the impact when you switch like what is the impact in terms of yield and scalability, if you can give us a color?

Yes. So Solid Biosciences was using an HSV manufacturing platform in the past. We have moved away from that platform all together, so none of our programs are on the HSV manufacturing system. Everything is now on to this triple transfection manufacturing platform. So the new generation, the next-generation Duchenne program, the FA program and all our cardiomyopathies are on triple transfection manufacturing. And we've taken the process that not only Solid worked on, but Aavanti 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. And just of note, we're a $97 million to $100 million market-cap company. We have a very decent-sized PD/AD team. We also have what I think it's critically important when you're thinking about manufacturing gene therapies. We have a regulatory -- a CMC regulatory team. So it's outside the CMC -- I mean out of regulatory strategy, it's a CMC experienced gene therapy regulatory team that sits embedded in our R&D, PD and 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 CMC is the drug, and it really changed the way the drug is not only distributed, but expressed. And we're getting if you don't change anything other than the manufacturing process, you're getting about 2x 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. So 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 and also 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 liters to 250 liters to 500 liters in our home office. So we have the ability to scale up to 500 liter. And then you -- as you go into the CDMOs then you can go to 1,000 or 2,000 liter, relatively easy. So that's one of the reasons we switched over, because it's very hard to scale up HSV, but not as much with a triple transfection.

So then if -- will you be thinking in the future will be -- you were using CDMO process or you wanted to do that internally?

Yes. So we're not going to get in the CDMO business. So we're going to keep that with them. It's just too expensive, too much of a burden. So what we did is -- what we're going to do is we have a very great -- we have a vector core that's down in North Carolina and the vector core produces all our small-scale material through mouse and some monkey studies. Then as the programs mature, we have the PD and AD teams, and that's the process development and analytical development teams that are embedded in-house in their headquarters. And 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 square foot of labs, full R&D, PD, AD teams, and we give tours all the time. So people can see the process. But we scale from 2-liter all the way up to 500-liter in-house. And then as we needed to make GMP material for 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. And so as you transfer from process development to the CDMO, we have a team, it's called MS&T, medical manufacturing science and technology team. And these are PD experts that sit on the floor of our CDMOs. And so 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 want to just hand it off and pray. We hand it off and watch. And we have teams. So we have -- we're in the middle of our GMP runs right now for first-in-human studies for our next-generation Duchenne program. We have 4 people that are literally sitting in Ohio in a hotel room and they go into the end of the Forge every day and watch. So it's making sure that for any program like our BAG3 program, it's very early stage. It's in -- it can really 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, then it goes to the vector core and then whereas we're getting into larger animals, it goes into our process development and then it goes into our CDMOs, and we have individuals that specialize in each one of those areas along the way. Highly focused on CMC. A lot of us worked at Sarepta in the past, myself, our 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 and that's what we built at Aavanti. And now it's within Solid.

Okay. Very helpful. So now going back, switch gear on your programs, the next-gen DMD program. So maybe since you have quite some modifications, the mutation or the peptide insertion. And what is the highest dose you tested in nonhuman primates and what kind of safety profile you see?

Yes. So we have not disclosed the doses, but I will tell you that we believe that we have dosed 2 to 4 times higher than we'll dose in humans in our nonhuman primates. So we believe it's 2 to 4x greater dose in the nonhuman primates. We have taken down all the nonhuman primates. I don't have the data. So there's nothing to disclose because I actually don't have it. But we started the GLP tox studies in December. We finished in early March. Obviously, it's mid-March-ish now. So we took down all the monkeys. What I can tell you is that all the animals from the time of dose to the time it take down survived. And we're doing very well until the take-down. Data pending, we have to do the bio analysis of all the data distribution and tox work, and we'll have that data in the next couple of months, and then we start working on the IND, writing the IND. But going back to your original question, we feel that we've dosed the nonhuman primate somewhere 2 to 4x greater than what will be in humans.

Okay. And that will be the human equivalent dose, right, 2 to 4x high.

Yes.

Okay. And then the -- what about the potency assay? I know Sarepta had some issue in the early development. And then I don't know if this is already relatively established...?

No, you have to have a potency assay. We've already contracted with a 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 it really sets the stage for your registrational trials in the future. You can't really move into registrational trials without a potency assay. So we understood that, and we started working on it immediately once I -- really, once we came in started working on this program within our GLP talks. We started working on our potency assay. So we've signed with a third party that works on these potency assays. We should have it ready by Phase I. That is our goal. But 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 to your registrational trials. But right now, we should -- we're planning on having it for a Phase I.

Okay. Good. And since this is a new capsid, any thoughts on existing neutralizing antibody when you go to the human, percentage of population there?

Yes. For this side of the capsid library, remember, I told you there's 2 sides. One side, we have not disclosed the parental capsid. On the other side, we have -- which was AAV9, and we modified AAV9 and that is where we found this capsid called SLB101 that's going into 003. So we are working on antibody assays, but our assumption is going to be that is directly overlapped with AAV9. So we have a third party that's doing antibody assay for us. It's well underway. It will be ready by our Phase I, because you have to have it for screening purposes. But our assumption is right now that -- it's identical to AAV9 or close to it.

Okay. Which means will be like 32%, maybe 40% -- it depends on the age?

It depends on the age, it depends on the study that you look at, I've seen studies in the low 20s as high as the high 30s. I think as you -- as these children age, you do see higher [indiscernible].

Yes. That makes sense. Now what are the additional steps you need to prepare in order to file R&D in mid-'23?

Yes. So we've guided to, what will we say, second half of '23 for IND filings and approval and second half for dosing. So 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 tox. Obviously, we did the mouse studies prior, taking down animals for the GLP tox. We have to wait for the bioanalytical data to come in once we analyze it, then we start writing the IND. GMP material is already underway for the first-in-human studies. We have to make the material. We've already completed GMP-1. We're working on GMP-2. Then that material, you need stability at 3 months, stability at 6 months. and then we file the IND after it's written. So you're looking at second half of the year, IND; second half of the year, hopefully dosing.

Okay. Good. And then what learning you can get from -- because we've seen already Sarepta moving very fast, and they have a Pfizer program and the previous Solid program. So any thoughts on for the Phase I trial design? .

Yes. So our Phase I, so we do have big ambitions of how we can think about the future of where we can go, what populations we can go in. But originally, we've got to focus in on safety. And so our first -- we're going to dose roughly 8 to 10 patients under Phase I. And that will focus on safety and microdystrophin expression, probably using a mass spec, and then we'll look at dystrophin positive fibers. That will be Day 90. So 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. And that's going to 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. But going back to your question, what do we learnt. One, baseline characteristics and selection need to be really scrutinized. If you go back to Solid's original program, which was 001, we dosed children from ages 4 all the way up to 14, weights as low as 17, all the way up to 40 kilos. We're not going to do that. We're going to really narrow down the age, make sure that we understand the mutations behind each one of the kids, because every mutation acts a little different, understand the baseline microdystrophin as well as baseline characteristics on NSAA, 6-minute walk test. All of this is going to be as tight a range as possible. It might cause the patient enrollment to slow down. However, 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, what's the data rates have. That's what we're into.

Okay. And will you do [ prophy Soliris ]?

We haven't decided -- I mean, obviously, we're going to use steroids. We have not decided if we're going to use another agent sirolimus or anything like that. More to come. We are -- one thing we know for sure, we want to keep these kids safe and out of the hospital, the best we can, because I believe that Duchenne has a long ways to go and I'm rooting for Sarepta's drug to get on the market, because I think it's going to help these kids. I also think it's going to create a surrogate marker for clinical benefit from the FDA, and that opens up a lot of possibilities of where we can take these programs in the future.

What about Ultragenyx [indiscernible]?

Yes. I don't know their program. I came in, in December, I did it 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, in filing IP and making sure that we know what broadly what's going on. But it's their program. I don't know the details.

Okay. So completely independent. Now, we have a few minutes, I wanted to ask your cardio program. So maybe the rationale using for the FA program, the rationale using CBA promoter?

CBA is a promoter that was originally with the program. It looked very good from a transduction in the CNS. And we believe that you should -- we feel very comfortable that we have a lot of the data that we can modify the cardiac aspect of the disease. But 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. The majority of patients have the CNS neuromuscular aspect of it. We wanted to understand if we can dose nonhuman 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 hard. So we have completed a 40-plus nonhuman primate study. It was a 6-month study. And we did multiple doses, multiple routes of administration, IV-only IT-only, dual route administration, so 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, because we can get into therapeutic ranges without getting the toxic levels. Now we're going 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 4 different cardiac programs. Our lead one is BAG3, BAG3 codes for this BCL2 associated with enthanagene3 protein. It is -- if you have a 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 1, 50% mortality in year 5, 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 to 10,000 patients. It's a huge population seeking treatment. We're using RH74 with a cardiac-specific promoter. We partnered with Dr. Adler out of UC California, San Diego. You may know him from the Danon program at Rocket. His entire lab is working on this program for us. We're going into nonhuman primates. Well, we've ordered nonhuman primates, so everything is backordered or hopefully you're going to get the nonhuman primates in the next couple of months, and then we start our program there. But we're very excited about the cardiac programs, we have 4 in the cardiac library. And we believe in the next couple of years, we're going to see that pipeline, that part of pipeline explode.

So the cardio programs in a little bit earlier stage development. So at what point like, say, 2023, like how much the animal data we will see?

If we can get to the nonhuman primates, we go in nonhuman primates in our BAG3 program as soon as we get them. I almost slipped up and told you the other program. But in hypertrophic disease state, cardiomyopathy, we were looking at next round of nonhuman primates at the end of this year to early next year. And then our third cardiac program, it will be early '24 for -- early to mid '24 for our nonhuman primate work. So this year, we'll be BAG3, 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 nonhuman primates this year. So you'll have that data, and then we'll be first-in-human in Duchenne. And then FA, 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. We look for a question update later this year. .

Yes, thank you. Thank you very much for the invitation. I appreciate it. Thank you.

Thank you, everyone.