Dyne Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Terrific. Thanks, Mike. I will just mention a little bit about where we are at Dyne right now. It is an incredibly exciting time for us. This company, over the last couple of years, has been preparing for the moment right in front of us, which is to launch a very important medicine in DMD, and that is early next year, followed by DM1 the following year. So we have been building a, I guess I would describe it as a pure play, neuromuscular, standalone, fully integrated biotech. Over the last year and a half, we have built out our leadership team and brought in people that I think other people that know how to build a company like this. They have been part of this type of company in the past, the company we are building for the future.

We know how to allocate capital, and we know how to launch products, and we know how to commercialize. We came here, really, and I came here because we want to launch two really important medicines in neuromuscular diseases where there really is nothing that is helping these patients. It is an extraordinary time. We have got a PDUFA date in January, and we are working hard to be ready to launch our first product.

Well, DM1 is one of those diseases where there is really nothing for patients, and it affects tens of thousands of patients. There's probably 30-plus thousand individuals that suffer from that disease. It shortens their life by about 2 decades, and they struggle, and they suffer. Our company had introduced zeleciement basivarsen clinically some time ago in a trial called ACHIEVE. That trial, we presented data that had shown, first of all, that we were getting at the core fundamental biology of the disease, and that's incredibly important. This is what's known as a nuclear spliceopathy disease, so it's in the nucleus. We had designed our platform, the FORCE platform, to deliver broadly and deeply to tissue. We also had attached to that platform an antisense oligonucleotide. That antisense oligonucleotide gets to the nucleus.

What we showed previously, importantly related to that, was that we saw DMPK knockdown. That's of the mutant DMPK that's at the source of this issue. Knockdown of DMPK, we saw as a result splicing correction, and I don't think anybody else has been able to show that, where the mis-splicing is corrected. We showed that in a dose-dependent way. Then what we finally presented at the end of that multiple-ascending dose study was that we were seeing functional improvement across multiple measures. That functional improvement was represented by things like five-times sit-to-stand. It also was represented by hand myotonia with VHOT, and we even had shown improvement on patient-reported outcomes, known as MDHI, on 6 subscales that are arguably related to the CNS. That disease has a CNS issue that's very significant.

Our targeting moiety, which targets TFR1, is an antibody fragment, and that fragment crosses the blood-brain barrier, and it also gets broadly and deeply to muscle. I think it's got a very unique and differentiated distribution that's allowing us to see that kind of improvement across multiple measures.

Yeah. I think everybody knows, but their result indicated that they did not meet their primary endpoint on video hand opening time. We were surprised by that because VHOT tends to be an endpoint that moves very easily and it moves early.

That is what we have seen. We were surprised by that. I would still come back to what I mentioned before, biology really matters here. Getting to the core pathobiology of the disease is key. That particular medicine from Novartis uses an siRNA, which does not get to the nucleus. I think we have to realize we have two very different molecules. When we start talking about read-through, you need to start with Even though we are both using TFR1 and going after the same disease, we have a completely different payload, and our Fab behaves very differently than the mAb that they use.

I would start there. When we looked at our data, we had gotten to, in the multiple-ascending dose study, to fairly high doses. In fact, we are at a much higher dose of oligonucleotide than the other sponsor is using, much higher. The reason for that is that we found at a low dose, we would move VHOT, but we were not necessarily moving the other more clinically meaningful measures. So we kept dose escalating to a much higher dose. That dose escalation is largely possible because we use a Fab. With the Fab, we do not get the dose-limiting toxicities of anemia that mAbs tend to see.

So we could get to a higher dose, and we are well above where we think we need to be to move VHOT, and even to move measures potentially into the CNS.

Yeah. Listen, we see VHOT, and we're using VHOT, as an intermediate clinical endpoint. Our clinical development plan has been different than others. I think we have a very robust and fulsome clinical development plan as it's laying out. We're first doing accelerated approval, and we have a registrational expansion cohort in ACHIEVE with 71 patients, and we are using VHOT as an early indicator, in other words, an intermediate clinical endpoint, at six months. Our data previously has shown at six months, you move VHOT meaningfully.