Entrada Therapeutics 3rd Annual Guggenheim Healthcare Innovation Conference

Sure. Entrada is fundamentally based on a family of cyclic cell-penetrating peptides, which we've named endosomal escape vehicles, or EEVs. It started as a delivery mechanism company, and then, of course, it evolved into a therapeutics company. What makes these EEVs so compelling from a delivery perspective is that they are able to get through the cell membrane efficiently, and then escape the early endosome of the cell, and then reach the specific target that it needs to get to from an intracellular perspective. What we do know is that the PK of the EEV governs a lot of the different metrics around how the drug interacts with the body. Fast-forwarding, the company's initial focus is within neuromuscular diseases led by Duchenne muscular dystrophy, which I'm sure we'll talk about a lot, and a partnered program with Vertex, myotonic dystrophy type 1.

Sure. Yeah, 2026 was an interesting year for us, and obviously, we're kind of looking past that. But between, I'll say, today and through the first half of 2027, we expect four significant clinical readouts, and I'll break them down. The first one is our DM1 readout. That's the partnered asset with Vertex. Their phase I/II interim results will be released before the end of the year, and I think a lot of eyes are on that, especially because of their approach and the fact that it's Vertex. Also, DM1 is over 110,000 patients, and there's no therapeutic option for these patients, so a lot of unmet clinical need. The three additional readouts are based upon our DMD program. The first one will be our cohort one open-label data release for our 44 program.

That we will see before the end of the year, before the end of this year. Why that's important is because those patients will have been on drug for at least eight to nine months, and they would have received at least six doses. It's a really good opportunity to see how the drug is affecting these patients with DMD, and it's our lowest dose at six mg per kg. The second readout will occur in Q1 of next year, and that'll be our cohort two data for our 44 program, and that is at 12 mg per kg, so double the initial one. Our third will be before the end of the first half of 2027, and that'll be the second cohort of our 45 program.

A tremendous amount of value that could be generated over the next six to nine months for the company.

Sure, yeah. Well, first and foremost, I would start with the unmet clinical need, right? The 45, kids who have the 45 mutation, there's no real therapeutic option outside of the U.S. that's disease-modifying. In the U.S., it's casimersen or AMONDYS 45, which generates over $300 million in sales a year. That's the standard of care, so to speak, to, quote-unquote, "beat." We set up this first cohort to be a safety readout. We wanted to understand, it's two parts of a puzzle, right? Safety and then efficacy, and we established that with that five mg per kg dose. Now, these patients in the trial were quite young, roughly around six to seven years of age, and they're continuing to do well until the disease starts to take over. We did not expect a lot of dystrophin to be produced for these patients.

Mind you, casimersen is at 30 mg per kg, and it's dosed every week. For Entrada's 45 program, we're looking at, currently it's one-sixth of the dose, but it's going to be dosed every six weeks. There's a huge advantage there from a dosing perspective. Now, what we expect to see in the second cohort is a dose response. We want to get the dystrophin up a little bit more. We'll understand the PK/PD a little bit more. We obviously want to maintain that safety, but if we can get the dystrophin up a little bit more, and then maintain that safety, we can start to look towards functional benefit within the open label. I think it's the right setup. I think cohort one achieved exactly what we wanted to achieve, which was primarily safety.

We got a little bit of dystrophin, which is a good thing as well, too.