Solid Biosciences Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Yeah. Thank you, Arthur, and thank you, H.C.

Yeah. Thank you again. Solid Biosciences, we're a precision genetic medicine company. Our current platform is AAV gene therapy, and we focus on two main diseases, which is Duchenne muscular dystrophy as well as Friedreich's ataxia. We also have multiple other cardiac programs that are not in the clinic yet. We have them ready for the clinic, or one's actually in the clinic for CPVT, and other ones are getting ready to be in the clinic for TNNT2. But we're slowing them down. We're putting all our resources right now, head count money, toward the two main programs, which are Duchenne muscular dystrophy, it's called SGT-003, and then Friedreich's ataxia, it's called SGT-212.

We also have a capsid delivery platform in which we make capsids to change the course of delivery for gene therapy in general, and we work with academic labs to make sure that they have access to these tools. As new programs, as these institutions are making new programs, they're using the next generation technology instead of having to revert back to AAV8 or AAVrh74, et cetera. Very excited. Next couple quarters, big quarters for the company. We're going to be meeting with the FDA on one of our products, and then we're continuing to dose the FA program, which will lead us to an FDA meeting sometime in the first half of next year, and then we'll talk about a registrational trial for that program. Very exciting next six months or so.

Yeah. We're really excited about our program. Just to put it in perspective, microdystrophins have been around for a while, different versions of it. Jeff Chamberlain, Dr. Chamberlain out of Washington, created most of, if not all, of the microdystrophins that are out there, and he kept refining this over many, many years. Realistically, the last one that he settled on, the one that he felt was the best one is the version that we're using in 003. Why? Many of us, all of us in this room, we have a very long protein dystrophin, but all the companies are actually shrinking it down. When you shrink it down, you have to think about what you're putting into that construct.

We removed all the hinges, so we only have two hinges, and that gives the protein as much flexibility as possible when you're shrinking it down and it's entering in the tissue. Then we kept R16 and R17. Those are the repeat domain, R16, R17, so that way we can recruit for a protein called alpha-syntrophin. When you recruit for a protein called alpha-syntrophin, you can recruit and bind alpha-syntrophin to nNOS. When you have nNOS, it increases your blood flow, it decreases fibrosis. We also recruit for a protein called cavin-4 that increases calcium channel handling. We believe that this protein, this construct, is going to be the best one for the children as we increase microdystrophin. We use a new capsid that has never been used before, first in human, called AAV-SLB101. We call it POLARIS-101. This capsid was created in the lab.

Each capsid has about 60 of these RGD peptides. The peptides bind to 2 integrin receptors that we all have in our skeletal and cardiac muscle. We haven't really disclosed what those receptors are. Some people have guessed from patents. We try to keep it as quiet as possible, and because we're building an entire platform around these integrin receptors. But in this capsid, when you look at this capsid in both mouse model, non-human primates as well as patients, it looks like it has a broader distribution in muscles. So depending on the muscle in the mouse and the non-human primate, 3 to 5 times greater biodistribution than AAV9, like the diaphragm's 5 to 10 times greater. Human cardiomyocytes, you see expression about 19 times greater, so it's really tropic to the heart.

In humans, in the mouse, the non-human primate, and we believe in the humans, it's liver detargeting. You saw it in the mouse and the monkey. Of course, you can take down the mouse and the monkey. In the human, obviously we don't do biopsies in the liver. But what we see is ALT, AST decline from the time of dose. ALT, AST decline immediately. It goes down and to the right, and GGT stays flat the entire way. With those 53 boys, we see this trend continue. It's on our slide deck. You guys can go look at, the whiskers are there, and you'll see ALT, AST go down. And why is that important? Well, we can use that ALT, AST now for a biomarker for muscle degradation and destruction. And so these kids, they come in at baseline 300, 500 ALT, AST at baseline.

That's not due to liver, that's their skeletal muscle breaking down. And now we can track it. Because it's where we're retargeting, we can sort of watch ALT and AST decline, and we look at a whole host of biomarkers, and that gives us an idea that there's a lot of muscle integrity, that the muscle is shoring up. And that gives us confidence that long term, we're going to see clinical benefit in these kids. We're feeling really good. We've got to meet with the FDA in Q4, and then we'll understand what we have and what they think we have.

Yeah. For those of you who do not know, we use steroids and steroids only. All the kids on Duchenne, they are always on a low-dose steroids. It is typically 0.75 mgs per kg a day. That is every Duchenne child, because it has been shown to help and benefit the kids. At the time, any of the companies that are out there at the time, you boost up your steroid regimen, depending on the company that is doing it. Either us, we would go out 30 days with a higher steroid regimen. At 30 days, we start to taper. At 60 days, they are back down to the normal steroid dose for Duchenne. The other companies that are out there, they go out longer. They bump it up to 60 days, and then they try to start tapering down, from day 60 to day 90.

Obviously, we have seen some of the cases that have made the news in the past with certain drugs that are on the market. That typically happens somewhere right around week 5 through 8. When you have in cases with the other therapies of GGT increases, ALT, AST, they tend to even stay longer than the 90 days of boosted steroids. Other companies also use sirolimus and eculizumab, and that is challenging for children, for the physicians, for the families. Why? You have to be on vaccines. You have to give the child antibiotics. You have to have a certain physician that can prescribe sirolimus. You have to have another physician that can prescribe eculizumab. You have to monitor for the sirolimus, you have to really monitor the kidney. You also have to look for gut issues, I think is contraindicated in children under 13 years of age.