Entrada Therapeutics, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Okay, great. First of all, thanks very much for having us. It's been a great conference so far, and we love working with you and we really appreciate the coverage and everything that you guys do. Very quickly, I can start with some highlights. Entrada Therapeutics, we're a clinical stage biotech company. The company is based around our Endosomal Escape Vehicle platform, and we'll describe that in a little bit more detail in the coming half hour. We have multiple programs in the clinic in neuromuscular disease. We have two solely owned programs, our ENTR-601-44 and our ENTR-601-45 programs. These are for two submutations in Duchenne muscular dystrophy. We also have a partnership with Vertex Pharmaceuticals, and they are developing a molecule called VX-670 for myotonic dystrophy type 1, DM1, all based around the same Endosomal Escape Vehicle.

Very briefly, what that Endosomal Escape Vehicle does is when we conjugate it to, in the case of our neuromuscular programs, an oligonucleotide, or in the case of other programs, maybe a protein, peptide, et cetera, what it does is it enables remarkable levels of endosomal escape. What does that really mean? What it means is when you're trying to get biological material into a cell, it's very difficult to get it into the cell. The cell is built to keep biological material out that it doesn't want. When it gets into the cell, it goes into a little structure called an endosome, a little soap bubble of a structure called an endosome. Normally, what happens is almost nothing gets out of that endosome. The cell doesn't want it to. It gets broken down, it gets kicked back out of the cell.

What our technology allows is 50% of that material gets out of the cell and then gets to the target in the cell where it can do its work, and that's compared to the standard, which is 1%. Our differentiator is really simple arithmetic at the end of the day when it comes to that. Where we are with the programs. 60144 and 60145, we'll talk about them in great detail going forward. But we are beginning to read data out on these programs, and you will see a cadence of clinical data coming now over the coming months. Very briefly, in 2026, we read out our first data, our multiple-ascending dose data for 60144, earlier this year, where we saw wonderful safety. We were very excited about that. And we saw some early functional benefit, which was a surprise, but a great surprise.

Coming now, we will have the cohort 1 multiple-ascending dose data for our ENTR-601-45 program, our second clinical program, and that should be coming in October. We are very excited about that. We expect that to continue to show safety, and we will see what the PK/PD looks like going forward. Following that, we will then be showing our open label data from our cohort 1 for ENTR-601-44, going back to ENTR-601-44. The reason that data is really important, and why we are really excited about that data is because not only do we hope to see ongoing safety, but we also hope to see an ongoing maintenance of the functional benefit that we saw in our early data. The question we got around our early data was, it was a 6/2 design, so 6 patients on therapy, 2 placebo. The signal was incredibly strong, time to rise Right how quickly the children can get off the floor.

It looked like they improved, in significant fashion versus placebo. But it is a small trial. You never know, right? If we continue to see this benefit over the course of the year, on 6 additional doses, we think that will be a remarkable signal that early functional benefit is real. That is a real drug effect. In particular, if we see our placebo patients who got worse start to flatline and get better, well, then that is even more impressive, especially because these patients should be getting a lot worse over the course of the year.

Right. That is why that readout is really exciting and really important.

The next two pieces of data will be our cohort 2 data. We are dosing our 44 patients at 12 milligrams per kilogram right now, so double the dose that we saw in our cohort 1 data, and our 45 patients at 10 milligrams per kilogram, so double the dose in our cohort 1 data. What we hope to show there is, of course, ongoing safety, but also a dose-dependent response with respect to key biomarkers like exon skipping and dystrophin, and potentially also function. Really exciting several months coming up.

I'll turn it over to our chief scientific officer.

Yeah, thank you. When we look at EEVs, our Endosomal Escape Vehicles, there's a library of peptides, and as Nate said, they're conjugated to the cargo. In the case of DMD, it is PMO. It solves several problems. One, when you take a PMO, which is about 10K in molecular weight below the cutoff for kidney clearance and no charge. When you infuse a patient with PMO, most of the drug ends up in the urine very quickly. Whatever gets into the cell gets stuck in the endosome. When you take the same PMO and conjugate to our EEV, then you see that 90% of the drug is still in the body even one week after infusion. The cellular entry process is greatly enhanced by the EEV. The second part is what Nate talked about, endosomal escape is also very, very robust.

You could get 25 to 50-fold more into the cytosol when you conjugate cargo into the EEV. For programs like for exon skipping, et cetera, we also had nuclear localization signal, and that takes the cargo to the nucleus where it needs to be for exon skipping. When you look at distribution of these EEV conjugated PMOs, you're right. I think apart from getting into the muscle fibers, we have shown that we get uniform restoration of dystrophin across the muscle fiber in animal models. Apart from that, it also is very, very good at taking the cargo into quiescent satellite cells. Quiescent satellite cells are very important in the whole biology of DMD because when a muscle is damaged, the satellite cells get more activated, and they're mobilized to the site of injury to repair them. For them to do this process, you need dystrophin.

If you have PMO in a quiescent satellite cell, then as soon as it gets activated, then the exon skipping happens, dystrophin is produced, so it can move the replication into a symmetric division, which is what is required to repair the muscle. Asymmetric division will just lead to more satellite cells being produced. That's what is very exciting about our technology, it solves several problems. Apart from that, duration of effect is also quite impressive.

Yeah. We can dose patients once in 6 weeks compared to once in a week for a naked PMO.