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

Good morning, everyone. My name is Gena Wang. I'm SMID cap biotech analyst at the Barclays. Thank you very much for joining the 7th Gene Editing and Gene Therapy Summit at the Barclays. I would like to first take this opportunity to thank all the investors, companies, also, especially our event team and the corporate access team who made this event possible. With that, I would like to introduce our next presenting company, Solid. With us today, we have Bo Cumbo, President and Chief Executive Officer. We also have Kevin Tan, Chief Financial Officer. Thank you both for joining us today.

Thanks for having us.

Thank you, Gena.

So maybe, Bo, I will start with DMD programs. And I think we have recently had quite a few recent like new updates, right? We saw the FDA Ad Comm, and we anticipate potential for gene therapy approval. So now they actually also mentioned nNOS at the FDA post-briefing document and the panel discussion. And so maybe from your end, what do you think now given current evolving dynamic? Like how do you see your DMD franchise now? And how do you want to advance your next-gen program into clinic? And what will be the most efficient way or the most commercially viable way?

Yes. Thank you very much. Very excited to be here, first and foremost. Yes, we're very excited about our next-generation program. There's obviously a lot of news around DMD right now, and rightfully so, definitely high unmet need where we got to get these drugs to these children. Obviously, there's one Ad Comm that recently happened. Ironically, that did not change our current plans at all, regardless of the outcome of what happens. We're focusing on our next-generation Duchenne program, and which we're really working on a novel capsid -- with a novel capsid, the transgene from the SLB001 program. And we have shifted over to triple transfection manufacturing platform. And our goal for this is to create a program that can not only hit antibody-positive children and bring microdystrophin to them at significant levels, but also think about ways we can deliver microdystrophin to children who have antibodies already to these capsids before being dosed, also to older children, how we can look at older populations, ambulatory or partially ambulatory. And these are heavier kids, they've been on steroids their whole of life, and how do we get drug to them, diaphragm, the heart, the intercostal muscles, et cetera. And then, obviously, there's going to be children who do not respond one reason or another, or respond and need a redosing regardless of the outcome. And so we're working on ways to approach those children. Now our first in-house trial will be for antibody-negative children. And our goal is to have an IND in Q4 of this year, and we will dose our initial patients at the end of this year in Q4 as well. There'll be roughly 8 to 10 children, antibody-negative, somewhere in the range of ages of 4 to 7 years of age and with multiple baseline criteria that we'll implement as well. And we should be dosing at the year-end.

And I assume -- given tenfold improvement, I assume the initial dose will be in the 13 range, right?

We don't know what the dose is going to be. We are doing a lot of animal work right now to identify the dose. I mean in the presentations I've already presented, we went all the way down to 3E13. I think we dosed 3E13, 1E13, 3E14. And yes, there's 3E13, 1E14 and 3E14. Those were the original doses we looked at. Ironically, all 3 of those doses had pretty much 100% across-the-board distribution in the heart, the diaphragm, et cetera, at day 29. We also saw a significant amount of microdystrophin expression at day 4, which was quite surprising to us. And it really comes back to the binding capacity of the capsid. And we can talk a little bit about that because this capsid is extremely unique and something that we created in our labs, and we believe that it is going to bring significant amount of microdystrophin expression to these kids. But going back to your original question, the dose. Our preclinical studies show that the -- regardless of the dose, we were getting very significantly high expressions. So we're continuing to do work, looking for a dose curve. With that said, we'll announce the dose when we have it. It will be later on this summer to early fall. But right now, I would expect that 1E14 would be the highest dose that we would need to go to, but it could be easily in the E13s.

Okay. Good. Very helpful. So since this is a new capsid, I know you based on some backbone there. Do you expect any major differences in terms of existing NAb-negative patient population to selection, the percentage of patients that could be neutralizing antibody positive?

Yes. The answer is we do not expect it. And we're doing some work with a third party on this right now, but we do not expect, and I'll give an example why. So one, there is cross-reactivity between AAV9 and AAV8, which is similar to Rh74 from an antibody standpoint. And this capsid, called SLB-101, is a modified version of AAV9. So we do not anticipate any differences in antibody cross-reactivity between AAV9 and SLB-101. Now what we did with SLB-101 is we created it to look at specific receptors. So we didn't focus on antibodies. We were looking at receptor activity within skeletal and cardiac muscle. And we inserted peptides and made point mutations specific for these receptors, all with the theory that binding capacity has a major, major role in expression and how we can overcome some antibodies. And we've done some work on that as well, and our hypothesis is correct. This is why we're getting so much significant increase in microdystrophin expression as well as distribution, but more importantly, we're seeing expression after liver transduction. So we're dosing, transducing and expressing all within a week, and we can see expression down to 4 days. And now we're doing additional studies to see if we can see it even before that. And so we're seeing more expression in 4 days than we would see at the end of the month with AAV9 with our first construct, so significantly different profile.

Very helpful. What is the highest dose you used in nonhuman primates? Or what is the dose-limiting toxicity there?

Yes. We have not disclosed the dose, the highest dose. I will tell you, though, it's two- to threefold higher than we anticipate the highest human dose to be, as I mentioned before. The 1E14 would be the highest dose that we would -- we believe that we would go, but most likely, it's going to start in the E13s.

Okay. So the question is more like from the safety perspective, what is like dose-limiting toxicity level? What is the highest you dose and then what is adult dose?

Yes. We haven't disclosed the highest dose in the GLP tox, but it's significantly higher than what we anticipate to be in humans. However, we dosed our nonhuman primates. We started that trial in December. That trial concluded in mid-March. From the time of the study start to the time of animal -- take down the animals, all the animals did very well. There were no unscheduled sacrifices. So it went as smooth as we anticipated. We did not see anything in the trial that would give us concern. However, I do not have the tox report yet. I will get the tox report very soon. I'm hoping within the next couple of weeks. We did end the trial at mid-March, but I don't have a full tox report to provide anybody.

Okay. Good. And then since the Phase I initiation will be very soon, I'm pretty sure you thought about the prophy regimen. Any thoughts on SOLIRIS prophy?

No. I think we're going to let the animal studies dictate sort of how we think about it. But based on what we've seen to date, because this capsid is also liver de-targeting, if you think about it from a dose standpoint, even if we end up at 1E14, that's significantly lower than Solid's original 001, which was 2E14. It's also liver de-targeting, about one- to twofold liver de-targeting. So you're going to get -- the impact to the liver should be about 1/4 of the amount that you have with the original 002 program -- or 001 program. So with that said, we're going to let the animal data dictate it. Right now, our current regimen will be steroids only. We will look at it to see if we want to augment this with [ stromas ] or something else, but we'll decide that later.

Okay. Very helpful. I know you do have Ultragenyx collaboration with your construct. Any update there? Any -- do you think why that would still be a good backup strategy at this point?

There -- we've not disclosed any of the relationship, the partnership with Ultragenyx publicly, but they've been a very good partner. We're in constant communication and collaboration with them, and we're all rooting for the children first. And so any program that can help make a difference in these kids' lives, that's what we're all trying to do. So they've been a great partner. Their programs -- their program -- they have -- I don't know what their time lines are. We don't discuss them.