All right. Welcome, everybody, to the fourth day of the 41st annual JP Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by Malcolm Cuno and Priyanka Grover from the team. Our next presenting company is Solid Biosciences, and presenting on behalf of the company, we have CEO, Bo Cumbo. Bo?
Thank you, Anupam. Thank you, JP Morgan team, for the invite. Really do appreciate the opportunity to present. Before we go into the presentation, let me take a moment to talk about forward-looking statements. These forward-looking statements involve risk and uncertainties, many of which will be out of Solid's controls. Actual results could materially differ from these forward-looking statements. Please take a look at the slide deck. It's posted on our website as well as the 8-K this past week. With that said, 2023 is going to be a transformational year and very meaningful advancements for the Solid Biosciences. We just completed a merger with AavantiBio, and I'm gonna talk a little bit about that.
That merger has really helped us think about a strategic pipeline of programs that are gonna continue to evolve over the course of 2023, with anticipated milestones in 2023 and in 2024. Let's just take a look at Solid Biosciences at a glance right now, and I'm gonna go to in-depth on each one of these topics through the presentation. As I mentioned, we completed the merger of AavantiBio, December 2nd of 2022, roughly about a month, a month and a half ago. Headquarters are now in Charlestown, Massachusetts. Now we've already combined the two companies together from a pipeline, novel capsid development that I'm gonna go into, as well as the expertise and the personnel from both companies. Now, our pipeline that we'll talk about today starts with SGT-003.
This is gonna be our next generation Duchenne program that's utilizing a novel capsid called SLB101. We expect our IND second half of the year and first patient dosing second half of this year as well. Our second program that we'll talk about today is Friedreich's Ataxia, we're using this is AVB-202, we're trying to work on both cardiac as well as neuromuscular CNS manifestations from this disease. We're doing this by a dual route administration because it's important not only to get frataxin expression increase, but also the distribution of expression over time. Third program is BAG3. This is our first program that's gonna be coming out of our cardiac pipeline. We have multiple cardiac programs we're gonna be working on in 2023.
BAG3 was the first one we announced. We're using a RH74 capsid with a specific cardiac promoter that we have not disclosed. All of our programs, by the way, the SGT-003, FA, cardiac, are on triple transfection manufacturing process across the board. Both companies were working on capsid libraries 'cause the next generation programs all start with delivery. I'm not gonna go into depth about them, but we're developing these next generation capsid libraries with two different strategies, and we're very excited about the results that will continue to come through in 2023 as well as 2024. We're well positioned for success in the next couple years. We have additional programs that will be announced in 2023, mainly from the cardiac side that we've been working on.
We have roughly $214 million in cash. This is unaudited as of December 31st. This will take us into 2025. The teams, as we've merged the two companies together, the team, the executive team is really well-known in the industry, not just in biotech, but more importantly in rare disease, precision genetic medicine, or in gene therapy. They've come from great companies across the board. I'll just highlight a couple of the names here that are sitting in the audience today. As you can see, the executive team from top to bottom, is really well done. We announced this week, Kevin Tan has joined us. He's sitting right here. He's our CFO.
Prior to coming to Solid, he was the CFO of Selecta Biosciences, and before that, he was the treasurer at Sarepta Therapeutics, along with Ty Howton and myself, who came from Sarepta before AavantiBio. We also have Dr. Carl Morris, who's sitting up here at the panel as well. Dr. Carl Morris is a neuromuscular specialist. He's a muscle biologist by training. He's been at Solid for about seven or eight years. Before that, he was at Pfizer working on a lot of their programs. As you can see, we are really stacked across the board. Of note, we have a regulatory Chief Regulatory Officer on the executive team.
I think that's extremely important in a complex environment that we're working in gene therapy to have someone who has expertise, not just in the United States, but globally, within the gene therapy space. Our head of tech ops, who's also on this slide, Paul Herzich, he's a gene therapy manufacturing specialist. Prior to AavantiBio, he came from BridgeBio. He was the CMC, the vice president of CMC for BridgeBio, and before that, Logic and Novartis. We have a very well-rounded executive team. It doesn't just stop at the executive team. You really need multiple layers throughout the team to really build a true platform company.
A lot of people say you have a platform company, but this merger has really put all the pieces together to do that. We have the ability to make constructs, new gene therapy constructs for new diseases, optimize those that transgene. We're working on promoters. You're gonna hear us talk a lot about capsids, where we're building our own capsids for next-generation delivery. We have vector cores as well as PD labs that we can make small-scale material on our own. We do not have to go to a CDMO. We have the ability to go up all the way to 500 liters in-house. We really do have a platform, and you're seeing that platform come together now when you look at our pipeline.
Our pipeline starts with our Duchenne program, our next-generation Duchenne program, followed by FA and BAG3 that I'm gonna go into today. You can also see we are working on multiple cardiac programs that have not been disclosed. A few of those will be disclosed first half of this year. One of the best parts about putting the two companies together is this next-generation capsid delivery platform that we were both building independently, and now we've merged them together. They're two very different approaches, but we're gonna be able to combine the capsid library together over the course of 2023 and into 2024. On one side of the screen, you'll see the cardiac capsid library that we're working on, looking at multiple libraries using unique barcodes and artificial intelligence.
Then with these barcodes, we have three different animal species that we'll work on in 2023, 2024. That'll be mice, non-human primates, and pigs. Looking for RNA-positive cardiac selection and then DNA for negative liver selection. That's for cardiac. On the other side, for skeletal muscles, we're taking a very ground-up approach, where we're doing point mutations within capsids as well as peptide insertions, and we're looking for speed of delivery. Speed of delivery in the next phase of Duchenne is going to be extremely important, and I'm gonna talk about that. How fast can we deliver the transgene and express proteins as quick as possible? This is where our capsid came out of for our next-generation Duchenne program.
It came out of the library that Carl has been working on, using peptides and point mutations. I'm gonna talk about that. Combined, this is going to be a very powerful platform that's gonna continue to evolve over the course of 2023 and into 2024. We will use this platform not only for internal programs, but out-licensing, for non-dilutive financing, once we have all the animal data in hand. Manufacturing capabilities. We took the best pieces of both Avanti and Solid and put them together. We have every aspect of manufacturing that you really need to think about when you want to be a platform-based company. We have process development teams, analytical development teams, and we're very, very fortunate that we have gene therapy CMC regulatory teams embedded in each one of our programs right from the very beginning.
In this complex world dealing with regulatory agencies and gene therapies, you need to have a sight on regulatory right from the beginning from a CMC standpoint, and we have those teams in place. We also have our CDMO partners across the board for FA, for Duchenne, for BAG3. It's one thing to have CMC partners, CDMO partners. It's another thing to make sure that when you hand it off to them after your process development, that you have very established MS&T, manufacturing science and technology teams, embedded into those CDMOs, and we have that in place. We also have a vector core that can produce small-scale material for our research teams. Two to three different constructs per week can be made.
That way, our R&D teams get the material they need for mouse models, but our PD, AD, and MS&T teams get to focus on the big picture of Duchenne, FA, and BAG3. It's already paying benefits to our first program, and I'm gonna talk a little bit about this. We have switched Solid's old first-generation zero zero one program, and we have moved it into zero zero three, which have moved into triple transfection and optimizing a capsid. As you can see here, we have already can show multiple-fold difference compared to AAV9 and our first-generation program by tweaking the process development as well as changing the capsid. We're very pleased about the process changes and how this could affect our microdystrophin program or FA or any other program that we're working on.
I wanna let you know that we're well positioned for strategic pipeline growth, and we have an eye on BD, not only internally for bringing in programs internally, but also looking at opportunities externally as well. We take a very hard look at the different indications that we are putting into our pipeline, and we have a commercial lens right from the beginning, making sure that once we think about all the indications and the reimbursement, that we have a significant amount of population within our indications for once we hit milestones, that they should have major inflection points for our investors. We have all the internal capabilities. We're continuing to build our network, and then we have the strategic manufacturing in place. You already see that within our pipeline.
First program is going to be our next-generation Duchenne program that I'll talk a little bit about, followed by FA and our third program, BAG3 dilated cardiomyopathy. As you can see, we have two other cardiomyopathies that are listed here that will be announced sometime this year, one for dilated cardiomyopathy, another for hypertrophic cardiomyopathies. Let me go into Duchenne. This is going to be our next-generation program, and I know many of you know Duchenne, so I won't spend a lot of time on it. It's caused by this mutation in the dystrophin gene, which leads to the absence of dystrophin program protein. Once you have this absence, the child unfortunately lose their ability to walk in their early teens and then succumb to respiratory and heart failure in their thirties.
There's roughly 10,000 patients in the United States, but more importantly than saying 10,000 patients is the subset of patients that's below that number, the early children, three to seven, that are naive. The children that have antibodies right from the beginning to all the programs that are out there. It's the older patients, and there's subsets of older patients that are non-ambulatory with low ejection fraction or respiratory failure. How are we going to dose these children? Because they're all not gonna follow the same disease progression. Our plan is to drive functional micro-dystrophin expression as fast as possible. We're gonna deliver what we believe will be the best-in-class transgene. How are we thinking about this when we create our next-generation program?
We took the best pieces of what we thought across the board. We put them together. We started with our transgene. This is the same transgene that Solid was using in their first-generation program. Why did we keep this transgene? You're going to see publications and presentations come out in this first half of this year where we're going to be presenting data for those patients that they dosed in the 001 program, their first-generation program, out to three years. We have patients that are going to have three years' worth of data, two years' worth of data, and one year worth of data. What you are going to see in that presentation and in that publication is that compared to natural history, six-minute walk test, pulmonary function, NSAA, across the board, these children are acting very, very different than natural history would tell you otherwise.
We're gonna take that transgene 'cause we know it works, and we're gonna put it in our next-generation program. We've switched to a new capsid, moving away from AAV9 into this SLB-101, this peptide insertion with point mutations, because it drives expression very, very quickly, and that's extremely important when you're thinking about the world where you might have to redose, and I'll talk a little bit about that. We've changed to triple transfection manufacturing process. With these changes of capsid as well as triple transfection manufacturing process, you can see that we're already having increases, dramatic increases, in the micro-dystrophin compared to their original program. Now, why is it important that we drive expression very, very quick?
Think of a world where we have to work on redosing or children that already have antibodies to these drugs or older children who have low ejection fraction or pulmonary function. How do we think about giving them different doses and coming back over and over again to make sure that we can drive expression? It all starts with, can you transduce in a very short window? Can you transduce and start to express in a very narrow timeframe, so you can drive down these antibodies? We can show now with our new capsid in four days, that's the top bar, in four days, we can drive transduction, has already occurred, because this is expression. We're getting almost 75%-80% or some of the mice, 100%, dystrophin positive fibers by four days.
I've never seen this data before, in Duchenne, I think it's pretty significant because it gives you the flexibility to start thinking about how we can get into redosing down the road. At 30, 29 days, across the board, minus a couple of mice, across the board, we can drive expression very, very quickly. This is dystrophin-positive fibers, so this is not Western blot or anything like this, just how many fibers are positive. We also can see this capsid is acting very, very differently than our first-generation program. On the left-hand side is biodistribution, in the middle is expression, and on the right-hand side is disease progression, looking at CK. In children, CK fluctuate up and down because they're running around like crazy because they're feeling good after they get dosed.
In a mouse model, at 29 days, it is a very good point to where you look at disease progression. You can see pretty dramatically that our SLB101 or our 003 program is acting different than our first-generation program. From biodistribution, fold change above AAV9 across the board in the quad and heart is different. However, it is liver detargeting compared to AAV9 as well. Micro-dystrophin expression in the middle, you can see. Now, this also translated over to non-human primates. This is a reporter transgene, but you can see from skeletal muscle, cardiac muscle, and liver, compared to AAV9, significant increases in biodistribution in the skeletal muscle and cardiac, however, liver detargeting as well. We have dosed our GLP tox non-human primates, where it's a three-month study.
We're not halfway through, but we're close to being halfway through. As of this morning, all the animals are alive and well, doing well for this GLP tox, and we're using this capsid, this transgene, et cetera, and we'll have additional data that'll be coming out later this year. FA, if you don't know FA, it is a very serious disease, monogenic disease caused by the loss of frataxin. When you have this loss of frataxin, you have. One of the most important things to understand about disease, it is a multisystem disease. Both the CNS and neuro manifestations, as well as the cardiac manifestations are very severe. It's roughly 8,000 patients.
Our approach is to make sure that we tackle the entire disease population, all the patients from the CNS and neuro side as well as the cardiac side. We're doing this by dual route of administration, trying to increase frataxin across the board, because it's not just the amount of frataxin that's needed, but it's also the distribution of frataxin to the affected areas. I'll show you some of the data. This is on the cardiac mouse model, and we feel very comfortable. You know, frataxin, if you overexpress, you can get to toxic levels. What you wanna do is you wanna push the dose as high as possible to understand what those frataxin expression limits are and then drive the dose down. We started in the E 14s, and we're already down to the E 12s.
This, the lowest, the best dose on this is 6E12 via IV. We can increase ejection fraction. We can increase survival. We also think that we can actually go a little bit lower, and we're gonna continue to tweak this as well. One thing of note, we wanna make sure that when we're restoring frataxin, that we're restoring the health of the mitochondria, and that's what you see on the right-hand side of the screen. Succinate dehydrogenase. In patients who have FA, when you do autopsies, and you look at the mitochondria and the DRGs in the heart, succinate dehydrogenase is completely depleted. We wanna know, can we restore the health of the mitochondria? By increasing frataxin, we can restore the health of mitochondria and restore ejection fraction and survival.
We think it's extremely important, as I mentioned before, that we look at long lengths of frataxin expression over broad range of targets, because it's not just the amount of frataxin, but it's the distribution of frataxin. This is a six-month non-human primate study, it's a long study. It's a lot of animals. What we did is we took multiple doses, but we also dosed them three different ways: IT only, IV only, and dual route of administration. We could understand if we can get to a nice therapeutic level, therapeutic range within the cardiac as well as the DRGs by doing this elegant distribution of dual route administration. We feel very comfortable that we have tackled the cardiac side.
We're still gonna continue to work on the CNS side in 2023 as we move forward into our IND-enabling studies. This was a big study, and this helped solidify that dual route of administration can provide frataxin expression to a broad range of targets without increasing toxicity. Our third program is BAG3. This will be our first cardiac program coming out of our pipeline with others to follow. If you don't know BAG3 codes for this Bcl-2-associated athanogene 3 protein or BAG3. When you have reduction in BAG3, you end up with dilated cardiomyopathy, and you ultimately have heart failure. This is a very large population, 29,000 patients in the United States, high incident population per year as well. If you have reduction in BAG3, your life is severely impacted. Eventually, heart failure sets in.
Once you're symptomatic, 25% mortality in the first year, 50% in five. If you are a patient, you are seeking treatment for this disease state. We are taking a approach using RH74 as our capsid with a cardiac specific promoter. As I mentioned before, all our programs are triple transfection across the board. We looked at multiple different aspects of this. We looked at multiple different capsids, multiple different promoters, and how do they all compare? This is just a subset of that data because we had a program that was using AAV9 with a specific promoter. We also had the program using RH74 with that same promoter. You can see on the left-hand side is biodistribution. On the right-hand side is expression.
First two columns are RH74, second two columns are AAV9, both using the same manufacturing process, and you can see significant differences. We think that we're well on our way with this program. We're gonna continue to evolve this program and tweak this program. We're working with an expert in the field, Dr. Eric Adler, out of UC San Diego, with his lab, and that program is ongoing as well. Of note, on the right-hand side, you can see that our program is liver de-targeting compared to AAV9 as well. We think that that will help us drive the doses lower. Driving to the future, last slide. What are our milestones this year? We are gonna complete our GLP tox.
I just told you, a couple minutes ago, we're not halfway through, but we're close to halfway through our GLP tox. All the animals are doing well. That should be completed in the next couple of months. We are gonna report functional data from the first-generation program that has been paused. Remember why. We're using that transgene from the first-generation program for our next-generation program. This publication is gonna show you that these children that have been dosed out to three years are acting very, very differently in compared to natural history, six-minute walk test, pulmonary function, NSAA across the board. From a durability standpoint and from an efficacy standpoint, you can feel very confident.
We're gonna have an IND submission second half of the year and hopefully first patient dose at the end of the year as well. We're gonna continue to tweak and evolve our FA program on the CNS side. We feel very confident we've nailed the cardiac side. We're gonna continue to evolve the CNS to make sure we get into therapeutic ranges, continue to transition from HSV to triple transfection, candidate selection for this, and move into IND-enabling studies as well. We're gonna be very thoughtful but aggressive on BD, on how we continue to enhance our pipeline, how we think about in-licensing assets that will continue to evolve Solid, and also out-licensing the cardiac capsids, the skeletal capsids for non-dilutive financing in the future. Of note, as I mentioned before, we have $214 million of cash that is unaudited.
That is of December 31st. We expect that to take us into 2025. With that, I'll thank you very much.
Thanks so much, Bo. Those of you who've been with us for three days know that there's three ways to ask a question, yeah? You can submit it to the digital conference book, I will ask it. You can email me, if you'd like to just go more old school, you can raise your hand, we'll make sure you get a microphone to ask the question. Bo, I wanted to start out just actually on a quick comment that you just made on business development. When you think about that in terms of your pipeline, early-stage pipeline today, would you consider clinical stage or mid-stage candidates versus, say, additional preclinical assets?
Yes. That's actually one of our goals this year, and we've already kicked off multiple processes of looking at opportunities to where we can augment our pipeline, get value inflection points, you know, early on. I think when you're building a precision genetic medicine company, you know, you need to stagger your different programs, especially from a gene therapy standpoint, because of the CMC. We're moving our gene therapy programs, you know, they're staggered by about 1.5 years apiece, and then we're gonna look for BD opportunities to augment our pipeline in clinical stage or very close to clinical stage, where we can get multiple inflection points over the course of the year. We're gonna stay within this precision genetic medicine realm, and we're gonna highly focused on neuromuscular and cardiac indications.
If it's something great comes across the board, we won't shy away.
On 003 in DMD, given the competitive landscape of, you know, Sarepta, Pfizer, and those products potentially coming to market as soon as this year, where do you see the pockets of unmet need in a micro-dystrophin gene therapy?
Yeah. I think, one, we're gonna let the data play out for Sarepta. You know, one, I think anyone who's into Duchenne is rooting for therapies to hit the market and change the patient lives forever, and that's our goal. We're gonna continue to evolve programs whether Sarepta's program or Pfizer's program gets on the market, continue to evolve and try to make best generations, you know, better programs that can help patient lives. We're gonna take a look at the data. You know, once we understand where the gaps are, where there's opportunities, that's what we'll target. Right now for our program, it's more important that we establish safety. We dose the next, you know, 10 patients in phase I. It could be 10, could be 12 in phase I. We establish safety. We look at micro-dystrophin expression.
We're very confident that it's gonna be different than our Zero Zero One program based on what we're seeing in preclinical models. Then we're gonna strategize on where is the unmet need based on the data that's out there, based on the landscape, we'll continue to adapt.
Questions from the audience? What are the gating factors right now to that IND submission in the back half of the year? Carl.
We're in the midst of the GLP toxicology studies and also the GMP manufacturing campaign is sort of kicking off. We just need to get the clinical material.
Where is that clinical material coming from, and how should we think about the progress to getting the commercial material?
We've announced previously that we're with Forge Biologics, as our CDMO. We've scaled up to 1,000 liters, we're just looking to that to continue to process material and release it.
Questions from the audience? Malcolm?
Maybe it's too early, but, 003...
Excuse me. Thank you.
Given that, various muscle tissues, you know, behave differently and we're probably gonna see, various degrees of duration, how should we think about redosing out there?
I think redosing is gonna play a very big role down the road in Duchenne, whether. We don't know the timeframe, you know. There's a large population that are gonna need some type of approach right from the beginning that already have antibodies to the different capsids that are out there. You're already gonna have to start thinking about a type of redosing strategy where you can knock down the antibodies as well. I'll turn it over to Carl for a second, but, you know, we're looking at multiple different ways to think about redosing. We're already in talks of different partners of how we can think about this. It starts with our program to understand, can we transduce and express within that first week?
When you knock down the antibodies, you don't wanna do it for extended period of time, especially with patients that are on steroids and have compromised immune system. What we needed to understand is with this next generation program, can we transduce within the next first couple of days and start expressing? We were completely surprised that we're seeing the expression that we're seeing within four days. That means transduction occur very early and expression. It gives us the opportunity, the flexibility to now find multiple paths. Maybe, Carl, do you wanna talk a little bit about that?
We've seen durability in the dog model out to about 3.5 years. I'm not sure about other programs, but it gives us a window for at least our program where we'll have to start thinking about redosing. It's a tough thing, but to remove. I don't think it's a safety issue, it's more about an efficacy issue where we just have to get rid of the antibody so we can get into the muscle tissue. I think that's where if we can create a window of about seven days where there's no antibodies, then we'll have a
I think the upside is huge of this new capsid with the way we're seeing compared to AAV9 from expression, from biodistribution standpoint and from liver detargeting, obviously from a safety standpoint, could be huge. Now we're seeing the transduction and expression within the first week. It opens up a lot of windows for the future. You know, all these boys as they get dosed, each one's gonna act different. You could see durability for some children go out further, you know, but others might be two years. You just don't know until the data plays out. We're building the next generation program and the market is gonna continue to evolve. This DMD market is big. It's, you know, multifaceted but beneath the surface. There'll be strategies for each one of these boys.
Two to 400 boys, in the United States are born each year with it, unfortunately.
Bo, we have a question in the queue actually, which is: What would be an ideal patient for SGT-003 in DMD with potential multiple other gene therapies and oligo competitors in the market?
Well, you know, I'm not gonna speculate on the ultimate patient. What I'm gonna do is we're gonna focus on establishing safety first, right? We're gonna get to this phase I. We are gonna take a younger population that will be naive, that are relatively healthy, and establish safety and micro distribution. At that point, we will work on the clinical development program and the strategy on who what patients we wanna go after and how. It might be very, very different depending on the competitive landscape and how we see the market evolving in the future. All I do know is that unfortunately, Duchenne is going to be here, and we're gonna have to continue to find new therapies to help these kids.
Questions from the audience? Right here.
The tissue and cell tropism is actually based on capsid itself or the gene expression under tissue specific promoter.
We, like with the original sort of, the gene therapy product in AAV9, we had a muscle-specific promoter, but now the capsid. We looked at about, you know, 10 to 20 targets, the proteins that enriched in muscle. Now we're going after for that. The SLB101 capsid actually is muscle tropic. Yes.
Is that from the protein receptor interaction, something like that or?
Yeah, something like that. Yeah. Peptide insertion, we looked at the target. We know what the target is and sort of went after that with a peptide insertion in the AAV9 backbone.
Any questions from the audience? Maybe a final one from me then. Bo, maybe on the broader pipeline, what are some of the key ongoing preclinical activities for AVB-202 and SGT-401 programs? Someday, do you see that the potential of these programs to maybe move up as kind of lead programs in the future?
Yeah. It's interesting question. I mean, you know, we're well advanced in our SGT-003 program, but our cardiac programs are pretty unique and moving relatively quickly. We took a very unique approach with our cardiac programs. I'm gonna sort of not sidestep the question, but I'm gonna come back around. We took a very unique aspect, approach to our programs. It tells you that, by the way, that we have a true platform. A lot of individuals, a lot of companies, including ourselves in the past, have licensed assets in from universities and bring them in, and then you develop them. We actually did it the other way around. We worked with the University of Florida in our own labs to develop the constructs. We optimized the constructs. We made the material.
We've dosed mice. We've filed IP, then we looked for leaders within the space in that specific disease state. For example, the BAG3 program, Dr. Eric Adler, he was the expert in there. The other two cardiac programs that are moving through the pipeline, we've partnered them with research universities that are specific for that disease state. Those programs are moving relatively fast. Do they pass our other programs? I don't know because I don't know the future. I just know that we are highly focused on these cardiomyopathies, but we're very excited about our next generation Duchenne program and the FA program as well. Look, you know, those are two big disease states.
We might need a partner down the road, and we'll start talking to, you know, companies about partnerships as the disease and as the data starts rolling in. I don't think we can boil the ocean and do all these, big, great disease states, independently. We'll be opportunistic on that as well.
Thanks, Bo and team.
Thank you. Thank you, Anupam. Thank you.