Welcome to H.C. Wainwright. Good morning, everyone. Welcome to H.C. Wainwright, twenty-sixth Annual Global Investment Conference. My name is Arthur He, a Senior Biotech Analyst with the firm. Thank you for joining us to have a conversation with the management of Solid Bio.
A little bit about Solid Bio. Solid Bio is a clinical-stage biopharmaceutical company focused on developing novel AAV-based gene transfer therapies for rare neuromuscular and cardiac genetic disease. To discuss the company's development strategy in the rest of 2024 and beyond, I'd like to invite Bo to this fireside chat, and also the Chief Medical Officer, Dr. Gabriel Brooks. Bo and Gabriel, welcome.
Yeah, thank you very much, Arthur. I really do appreciate it, and thank you, H.C. Wainwright, for the invitation.
Bo, to help set the stage for the audience who are not so familiar with the company, could you give us an overview about Solid Biosciences' pipeline?
Yeah. Solid is a very unique company. It's a precision genetic medicine company, where we originally were focused on one indication, which was Duchenne muscular dystrophy, and we've gone through lots of changes over the last two years, where we're really focused on multiple indications, not only in the neuromuscular, but cardiac space.
And we also invest a lot of time and effort on our platform for delivery, which is both not only from the manufacturing standpoint, looking at full-to-empty ratios, but also from our capsid delivery. So we have a platform of delivery technologies that we use, and then that translates into our clinical programs, not only for cardiac indications, but also neuromuscular, like Duchenne and Friedreich's ataxia.
Thank you. First of all, congrats on you guys starting the phase I to study of SGT-003. And also you disclosed very encouraging early safety data. Could you tell us more about SGT-003 and how it differentiates from other Micro-dystrophin gene therapy for DMD?
Yeah. So when we started working on this program, we knew that the first-generation programs were, you know, already on the way. They had not been approved yet, such as Sarepta's Elevidys, but it was getting close. And so we knew that we needed to build a true next-generation program, one that we felt could provide benefit above and beyond what was already on there.
So when you take a look at it, you break this program down, really, there's three components that we needed to look at for it to be truly next generation. The manufacturing process, which was one of them, the capsid, the actual delivery vehicle for the transgene, and then the transgene itself.
We've made changes to, you know, all of them, one way, shape, or form, to make sure that we have a true next-generation program. And we're excited. I mean, Dr. Brooks has already dosed a couple patients. We announced that a couple weeks ago. Patients are doing great, and now we're heading into our third patient, which will be later this month. And then he's already setting up. Dr. Brooks is already setting up multiple sites outside the two that we already have, and patients are gonna begin lining up for additional dosing.
That's very nice. So, we know, besides the AAV capsid, you also have made multiple improvements on the manufacturing for the SGT-003, as compared to your original version of the drug. So what are the potential advantage of your manufacturing capacity?
Yeah, so, you know, I... When we were building the last company we were at prior to Solid, we put a lot of emphasis on manufacturing. I fundamentally believe if you're gonna be a leader in the gene therapy space, you've got to be a leader in delivery, and we spend a lot of time on manufacturing, and we really, really focus in on this full to empty ratio.
And that's how many particles out of a hundred are complete from ITR to ITR of your transgene. So when you do dose your patient, they are receiving a active transgene. And so we spend a lot of time there, and I believe we have one of the best manufacturing platforms or delivery platforms for our drugs in gene therapy.
For example, for Duchenne, on a batch-to-batch basis, anywhere from 77%-81% full to empty. It's a pretty tight range, 77%-81% full to empty. For CPVT, we've made even additional advancements. We're in the 90s. And if you recall, back in the early days of biologics, you know, spend a lot of time on manufacturing.
I think we're at that stage now where we're changing the way, the paradigm of gene therapy because of the CMC and the delivery, and it makes a big difference. It makes a difference on safety. You're typically dosing, you know, patients on a vg/kg standpoint. So if I'm dosing you at 1E14, and I have a 50%-
Full-to-empty ratio, realistically, I need to dose you at 2e14 to get you to that true dose, right? That could put an impact on your liver, could put an impact on safety, so you really need to be careful. Where I don't have that issue, I'm at the 80%, so I really don't have to increase the dose that much. The other is obviously COGS, right? From an expense standpoint, our expenses should be lower because of this high full-to-empty ratio.
And then we have shown, and we've shown in our own data, and in human cell data, that when you dilute down, when you increase the number of partials or empty capsids, they still fight for the same receptors, and so they can block that transduction of a true full capsid.
So ultimately, efficacy is impacted as well. So by focusing on full-to-empty, as a company, I believe that it's not only helping patient safety, helping patient efficacy, but obviously lowering COGS, which we could hopefully pass on to the families.
Awesome. So let's take a little bit deep in the clinic. So before we doing that, could you help elaborate the study design of your INSPIRE Duchenne study?
Yeah, and I'll turn it over to Dr. Brooks. I don't know if you can hear him. I don't think he has a microphone, but we have currently open two cohorts, cohort one and cohort two. Cohort one is four and five-year-olds, and cohort two is six and seven, six less than eight. We are dosing those little boys right now. We've already dosed two patients in cohort one, and we're about to dose our third patient in later in September, and excited about that.
Now, I think we announced earlier, because of the demand, which we have a great deal of demand from patients trying to get into the trial, for this next generation program, and because our patients did so well, the first two, we've decided to expand, and really, not only expand in age, but expand in number, expand in sites, expand in countries.
And so we have two countries. We're filing CTA in U.K. We're filing a CTA in Italy this quarter. We already have our CTA approved in Canada, Q2, and site to be up and running in Q4. We're adding in three additional sites in the United States, and Dr. Brooks is gonna be recruiting a lot of patients in. So, Gabriel, do you wanna-
Yeah, thanks, Bo, and that's right. I think it's really predicated on the demand that we're seeing from the community for a next generation gene therapy. Having seen, you know, clinical signs in the first-generation gene therapy, really, folks are very eager to get to something that they can truly make a differentiated difference and improvement. And from that, we're taking this opportunity to expand our study and also learn from some of the earlier first-generation trials.
And with that, that is, as Bo had alluded, you know, really changing the patient population to expand it in terms of the age range, but also focus on those patients that are more predictably in a declining phase, so that we can really maximize our ability to demonstrate a clinical effect.
I see. So I guess we're gonna listen more about the specifics about the amendment later on, I guess.
Yeah, it should drop in Q4, and then once it hits ClinicalTrials.gov, we'll talk about it. We're excited about it. We just did ad hoc this weekend in London, and talked to all the KOLs about it, because we're gonna be expanding into Europe pretty broadly, where there's a lot of... unfortunately, there's a lot of demand because there's no access to other therapies there.
And they're very excited because we're gonna be in a broad population now, you know? It'll still be ambulatory, and that's what you'll see, but it's definitely gonna cover off a number of ages. And we're very excited right now 'cause we're in sentinel dosing and, you know, just one patient after another throughout the year, rest of the year, then we'll go forward with that.
Oh, thanks, Bo. So Gabriel, so regarding the initial safety data-
Yeah.
I know even it's very early. Could you give us more color about what you guys have seen so far in the clinic?
Absolutely, and thrilled to do so. Even though it's early, we, of course, pay close attention to the safety of these patients, and principally, you know, in those first couple of weeks, what you're looking for is inflammation that might be demonstrated by the capsid. And we did not see any significant adverse events with those first two patients, which is gratifying because it recapitulates the very safe profile that we saw in our non-human primate study.
I wanna dwell on that for a second because not only is that really important for SGT-003, this next-generation gene therapy for Duchenne muscular dystrophy, but also SGT-003 is using a novel capsid that's never been before in man, that specifically targets muscle cells for improved transduction.
Having demonstrated safety in these patients, not only de-risks SGT-003, but also de-risks SLB101, this novel capsid, which we're looking forward to use in future indications, as well as in partnerships with other companies.
Oh, thanks, Gabriel. So ... I could imagine in the latter half of this year, in the H1 of next year, we could see the ramping up of the enrollment in the study.
Yeah.
So how's the readiness for your manufacturing side for?
Yeah, so the manufacturing, we, you know, the great news with our manufacturing, we've been working with Forge. I mean, that's been publicly disclosed. We're already at a thousand liters. We could go higher, but there's no reason to go higher.
We're getting great yields, and we've made very modest changes from our original batch to the batch that we're gonna be using in this expansion trial that Dr. Brooks just went over. So, we're very pleased with the process, and we don't expect many changes, if at all, going forward. And hopefully, that's gonna matter when we talk to regulators down the road.
I see. So there's obviously a coming, upcoming catalyst for you guys, update the biomarker and the regulatory functional status data by the end of the year. So could you tell us what exactly the data set look like, and how would you... In your mind, what would the positive readout look like?
Yeah, I'll turn it over to Dr. Brooks in a second on the readout and what we're gonna be looking at. Let me tell you, you know, we've already dosed our first two patients. Clearly, we are going to have the biopsy after 90 days by the end of the year. The question that we're asking ourselves when we talk to a lot of investors, "Is two enough, or do you want three?"
You guys seem to always want more. So you know, our third patient, we are dosing at the end of this month, okay? And if you do the 90-day biopsy with added four to five, six weeks to do the analysis on the biopsy, that pushes the data into 2025, early 2025, January, February, if we wait for three.
If we wait for two, then we'll have the patients. If it's just two doses, you know, patients, we'll have it by the end of the year. So we're on track for our guidance. It's just, you know, do we want additional patient to sort of-
Yes
... round it out? And we'll be determining that over the course of the next, you know, couple months. But maybe, Gabriel, why don't you talk about, like, what we're looking at once we have the biopsy and the clinical data?
Yeah, absolutely. And just to expand a bit, you know, we are methodically getting these, you know, first couple of patients' data, and that's important from a safety standpoint, but also, you know, not to be conflated with demand.
There's, as much as we have a demand and an eagerness to start dosing patients, we're actually inundated with sites that are opening up, because investigators want to be part of this study and patients that are eager to participate. And from a FDA regulatory standpoint, we really are in this, what we call a dose-limiting toxicity period.
So that's why we're seeing, you know, the slow accumulation of these first couple of patients, and we expect to pivot soon so that we can have a much more robust cohort of patients come in shortly thereafter. With that 90-day biopsy data, yes, we're gonna be able to look at 90-day clinical markers of function.
But I think we just need to remember with these small numbers, it's really anecdotal. We're really excited to look at that, not only the functional data, but also some of the biomarker data, like CK and other things, LDH and other things that bespeak a, you know, less muscle damage, which we're expecting to see.
Gotcha. I'm looking forward to that. So let's switch gear a little bit to your next candidate in your pipeline, the target, the CPVT. So first of all, could you tell us, give an overview about this disease, and what's the potential market opportunity for that?
Yeah, and I'm very grateful that we actually have one of the, you know, experts in the field, in Dr. Brooks, in this disease. He's been working with the KOLs for many years, so we're very fortunate because we are already getting multiple KOLs, global KOLs, working with us on this program. And why is everyone so excited about it?
One, it's a highly fatal childhood disease. You know, kids get diagnosed seven to 12 years of age, and there's high mortality, up to 40% in the first decade after diagnosis. We hear of, unfortunately, children dying all the time. We have a chance to do something that has not been done in this disease state ever, and that's change the underlying cause of the disease.
Right now, you could utilize beta blockers, or flecainide. Beta blockers came out in the eighties and nineties last. I think the last newest update, the beta blocker was in nineties. Flecainide, it started being used in 2010. But, so realistically, we have a chance to do something that no one's done.
The KOLs are very, very excited about this prospect of using gene therapy and really manipulating calcium flow, and that's what we're gonna be doing, soaking up the excess calcium to get back to normal rhythm. But you have about twenty thousand patients in the United States, obviously much, much more ex-US. But so when you think of Duchenne, you know, this is a fatal disorder, as well, young, and it's as big, if not bigger, in the United States.
We're the only gene therapy company that, you know, that's in the space that I know of, and I think it's gonna be an unbelievable program with a high, high demand. Gabriel, do you want to talk a little bit about it?
Yeah, and just very briefly, if you're not familiar with Catecholaminergic Polymorphic Ventricular Tachycardia, it's a disease where, you know, adrenaline leads to unstable heart rhythms and either fainting or death. And really, the patients that are treated, even with beta blockers and flecainide, as Bo has alluded, there's always a sword of Damocles over their head, that they can have an event.
Sometimes it's because they're non-compliant, sometimes it's because they can't tolerate the side effects of high-dose beta blockers, like depression, weight gain, and impotence. And other times, they seem to break through, and that affects not only the patient and their quality of life, but their families as well.
And so gene therapy is a paradigm shift because this is a therapy that can protect the patient all the time. It's always there, it's their safety net, and liberate them, potentially, we hope to see this, from the medicines and the side effects of the medicines.
Yeah, this is a multi-billion-dollar opportunity.
So then, what's the next milestone coming from this program?
Yeah, so we're already in our GLP docs, and we're already in our proof-of-concept studies. We'll be reading those out later this year, and we'll have that data for you. Now, the FDA, we had guidance for an IND submission Q1 .
We changed that guidance to H1 . The change in guidance is because we had a great meeting with the FDA, pre-IND meeting, but they want a six-month non-human primate study, which is typical for new drugs and new indications in gene therapy, so we are underway, and we'll be submitting an IND H1 of next year, and then hopefully dosing patients shortly after.
Awesome. So besides these two programs, what are the other preclinical programs in your pipeline you want to highlight to us? What-
Yeah, I think, you know, we have three that we're really excited about. They're earlier. TNNT2, which is another cardiac program, BAG3, it's another cardiac program, and then we're still continuing to work on FA, to try to alleviate the symptoms of both the cardiac, neuromuscular, and the CNS manifestations of the disorder. So we have three that we're working on.
We have additional programs, too, you know, RBM20, but I guess, you know, first and foremost, that third or fourth program, TNNT2, BAG3, FA, and we'll determine which ones we move forward based on the data as they come in.
I see. Also, besides the specific targeted program, you guys are, over the years, have developing a broad, deep library of AAV.
Yeah.
Could you tell us more about how you guys plan to maximize the potential of this AAV library?
Yeah. We're working with the University of Florida. We've been working with them since 2021 on directed evolution capsids. We've never disclosed what the parental capsid was, but we already have 10 capsids that have gone through three different animal species, mice, non-human primates, and pigs.
And then we're taking these additional 10 capsids, doing additional work on them over the course of the next couple of quarters, and then we're going to determine which capsids we really want to incorporate into our pipeline. The rest are going to be, you know, hopefully licensed out.
Not only licensed out to small companies, but big companies, similar to what Voyager's doing. And then we'll give some of the capsids away to institutions to incorporate into their platform. You know, in three to five years, we hope to have a lot of our capsids out there across the world in many different programs.
Sure. So for closing, could you remind, besides the SGT-003, what's the other major catalyst we should focus on in the next 12 months for Zai Lab?
Next 12 months?
Yeah.
I think it's the expansion that you see that Gabriel's doing with Duchenne. We're going to be dosing a lot more patients, hopefully, starting in Q4, expanding a lot of additional sites, so you'll get readouts of, you know, progress there. You will have an IND, we believe, in CPVT in the H1 , plus all the data from the non-human primate and the proof of concept study. Then, hopefully, we'll announce our third program and third IND, and when we expect that to happen. You're looking at two to three, to potentially four INDs in the next couple of years.
I see. How about the cash position?
Roughly a 190 at the end of Q2, and that takes us into twenty twenty-six.
Awesome. Thanks, Bo, and thanks, Gabriel, to coming down to talking to us.
Thank you, Arthur.
Thank you.
I appreciate it. Thank you.
Privileged.