Good afternoon, everyone. My name is Susmita Roy. I'm an associate on the Healthcare Investment Banking team here at JPMorgan. On behalf of JPMorgan, first of all, thank you so much for taking the time to attend the conference. It's been a great conference so far. And to continue the festivities rolling, I'm thrilled to introduce Entrada Therapeutics and for their company presentation today. A little bit about Entrada before we get started. Entrada is focused on treating debilitating diseases with intracellular targets. Last week, Entrada highlighted important progress across its EEV portfolio for neuromuscular and ocular diseases. The company is advancing multiple clinical programs in people living with Duchenne muscular dystrophy in the U.K., EU, and the U.S. In 2026, Entrada expects to have four clinical-stage programs in its DMD franchise, complementing the ongoing clinical programs progress of its myotonic dystrophy type 1 partnership, VX-670, with Vertex.
The year is shaping up to have several value-driving catalysts. I'm pleased to welcome on stage, next to me, Entrada's Chief Executive Officer, Dipal Doshi, who can share more about Entrada's year ahead, and also on stage, we'll have Natarajan as well. Thank you for joining us this afternoon, and really pleased to hand it off to the team.
Great. Thank you. Thanks for the kind introduction and to the JPMorgan team for inviting us here to present. I look forward to talking more about the work that we're doing at Entrada. Before I go too far, it's the normal disclaimer about making forward-looking statements. So just refer to our SEC filings and whatnot that can impact our business. So I think I did this last year as well. First and foremost, we have a mission at Entrada. I think a lot of companies have missions. Ours has been intact for the past nine years, and it's to treat devastating diseases with intracellular therapeutics. And at the end of the day, these boys here on this slide here all have DMD. They've all been to our offices. We have pictures of them and their stories. And I think that's one of the most important things for me.
And I'm very fortunate to be able to interact with not only these patients, but also their families and understanding their journey and sharing with them, along with Natarajan and my colleagues from Entrada, sharing with them the progress that we're making to hopefully help themselves as patients and their families as well. So Entrada today has an expanding portfolio of intracellular therapeutics. We'll spend the most amount of time today talking about our Duchenne muscular dystrophy programs, our franchise. And we'll also spend a little bit of time talking about myotonic dystrophy type 1, or DM1. That's our partnered program with Vertex. And then last but not least, we did announce on Sunday an expansion of our focus into ocular diseases, which is really exciting for the team as well, too.
We're excited to expand beyond neuromuscular to really show the full strength of what Entrada can bring to the table. But this is one of those pipelines that can continue to expand. And as such, 75% of all disease targets are intracellular in nature. So you can start to imagine all the different opportunities and diseases that the Entrada team can go after. So I'll start. It's a busy slide. But when I stood up at JPMorgan last year, I said that 2025 would be a year where we are heads down as a company, executing to be able to put ourselves in a position to have multiple clinical stage programs by the end of 2025. So now I stand here a year later saying we achieved that.
We're advancing these four clinical stage programs to the point where we're going to have clinical inflection points with our ENTR-601-44 program, our ENTR-601-45 program, and our partner program with Vertex, which we call VX-670 in 2026. So going left to right, the momentum and the excitement around Entrada is building because we're getting close to that data. So in the second cohort, or sorry, in the second quarter of this year, our ENTR-601-44 program will share those data, that top line data from the first cohort. I'm pleased to announce that dosing is complete. The open label dosing has been initiated. And so we expect that first cohort of data in Q2. And then we expect the second cohort of data in Q4 or by year-end 2026. Our ENTR-601-45 program, we expect the first cohort of data in mid-2026.
So therefore, you can see in Q2, we expect data, mid-2026, we expect data, and by the end of the year, we expect data for our DMD franchise. We have a stepwise progress when we start to think about the diseases we're going after. Our ENTR-601-50 program is a little bit behind that, and that's staggered by design. We have received authorization by the U.K. regulatory agencies to go forward. We expect to file our EU regulatory applications this year as well. Lots going on, on DMD. Our 670 program with Vertex for DM1. Vertex has completed the single ascending dose portion of the global Phase 1/2 study. The multiple ascending dose portion to evaluate safety and efficacy is ongoing. I'm pleased to announce, per their announcement, that they plan to complete enrollment and dosing of this very important trial mid-year.
That partnership is a very robust partnership for us. Not only did it include a very sizable upfront, but there's a significant amount of milestone payments and royalties that are associated with that very important disease. From a pipeline perspective, based upon what I said about intracellular targets, we continue to advance this preclinical pipeline. We are pleased to announce, as I said earlier, our expansion into inherited retinal diseases, or IRDs, and we nominated our first candidate, clinical candidate, which we call ENTR-801 for a disease called Usher syndrome type 2A, which we'll talk about in a little bit. We also have a second program that's in lead optimization that we plan on announcing a candidate for in 2026. There are additional discovery efforts, kind of like the tip of the spear for us, where we will continue to expand in neuromuscular and ocular.
But we will also look at a range of undisclosed modalities and diseases as well as we continue to build Entrada into a leading intracellular therapeutics company. From a financial perspective, we ended 2025 with about $296 million on the balance sheet. And we have a healthy cash position that takes us into Q3 of 2027. So let's start with our neuromuscular diseases, and specifically with Duchenne muscular dystrophy. So our story and our strategy really is predicated on three pillars: differentiation, de-risking, and speed to global approvals. As many of you know in the audience and online, this is a devastating disease which ultimately leads to a cause of death, which is attributed to some type of cardiomyopathy. What we have in Entrada is a differentiated, what we call, Endosomal Escape Vehicle platform and also a novel PMO conjugate.
And what we've been able to see, I'm not going to read the entire slide, but what we've been able to see is a 25-fold improvement in endosomal escape, which resulted in non-clinical best-in-class efficacy. The novel PMO sequences that my colleague Natarajan and his team have developed are superior to the marketed PMOs, even without conjugating them to the EEVs. Our non-clinical data has translated into very compelling healthy normal volunteer PK data and safety data supporting the potential for even a more robust differentiation. Importantly, what we have learned is that there is an uptake that we can facilitate into the satellite cells. And we have a slide on that that we'll talk about. But that's really important when we start to think of how functional improvement will be affected by our EEV conjugated therapies.
And that is a distinct differentiation between us and some of the antibody-based therapies.
Importantly, when we start to think of these young boys that become young men, the amount of dose or the amount of drug that goes into their system is something that we are very careful about. Obviously, we want low dose with high concentration. And what we've been able to see when we compare ourselves to other companies is a drug load that is substantially less than the antibody-based therapies, which therefore then increases or decreases the risk of exposure and antibody response. It also, when we start to think forward, it also decreases our manufacturing burden as well. So when we start to think of, "Okay, great, great profile, but what comes next?" We are running all of these DMD studies outside of the U.S. And that was a very calculated strategy.
And so what we plan on doing is running these studies outside of the U.S., collecting those data, and bringing those data back to the U.S. to share with the FDA, and then, of course, enter the U.S. market. It's a very efficient, and it's a very fulsome strategy that has worked well for our 44 program, and we'll continue with the other exons. When we start to think of these Endosomal Escape Vehicles, they are very specific for neuromuscular diseases. And what we're excited about is the same EEV that we're using for our DMD programs is the one that Vertex is using for the 670 program. So a lot of synergies between the diseases as well.
When we start to think of what our expectations are, and we spent the entire day talking about this with investors, for the first cohort of data for our 44 program, we expect to see double-digit dystrophin production, which is really important. So we want it to be safe, and we want it to be efficacious. Efficacy in this case is measured by dystrophin. We feel as though that is the first domino to fall, in a good way. If we get both safety, which we expect to, and double-digit dystrophin production, which we expect to as well, we feel as though that sets up a translation to the other DMD exons, 45, 50, and 51, in that positive data in one ENTR-enabled candidate immediately de-risks the clinical profile, so really exciting when you start to generate these data.
Ultimately, our goal at Entrada is to get these drugs on the market and to get them to the patients, and so the ex-U.S. strategy really kind of enables a rapid acceleration of getting clinical data, and then, of course, helps us initiate discussions with FDA to discuss accelerated approval. That pathway is open in the U.S. That pathway is not open ex-U.S., so accelerated approval in the U.S. is something that we believe one is open, and two is something that we are going to strive for with all of our exons. This is fundamentally based on the opportunity to develop a best-in-class PMO across our portfolio, so when we think about a timeline, the accelerated approval pathway would be expected to coincide with a confirmatory trial outside of the U.S.
The team is really gearing up for a very, very busy 2026, not only from an execution perspective, but also from a regulatory perspective as well. Sorry. Let's talk about the EEVs, because when we start to think about these EEVs, they are distinct from some of the other approaches, including antibody-derived therapeutics. What are EEVs? They're a family of cyclic cell-penetrating peptides that have three unique characteristics. One, a very unique chemistry, which allows for an improved uptake into the cell and then escape from the endosome. The second, which is a cyclic structure in nature, allows us to increase the stability and also extend the half-life, which becomes important. The binding to the phospholipid allows us to enable a broad biodistribution to a plethora of cells.
What this has also shown to us in our studies, now, once again, this is across DMD and DM1, is both consistent and predictable pharmacokinetics or PK. So the character on the right exactly shows what we're able to do. So from an endosomal escape perspective, you don't want to get stuck in the endosome. You want to get out of the endosome so you can actually get to the muscle that you're trying to get to. We're able to do that at a 25-fold increase compared to other programs. So if you're able to do that, that means you have a bolus of material that's getting into the cell and getting into it at a 90% uptake, and then you're able to get out of it. So the more that gets in and the more that gets out translates to the more that gets to the muscle.
That's kind of like what the secret sauce is with Entrada when it comes to neuromuscular diseases. This is what allows us to get to the muscle at high concentrations at a very, very low dose. We show this here, too. It's not only about the EEVs. It's also about optimizing the active conjugate. It's a two-part thing. On the left part of the slide, this is a comparison against the R6 PMO, which is a competitor program. What you can see here is the EEV optimization is profoundly different when it comes to us versus this R6 PMO. Also, the optimization of the PMO itself or the conjugate is something that the team has worked on extensively. Now you have this double effect.
You've got a remarkable delivery vehicle, plus you also have an optimized PMO that put together allows us to generate the data that we've generated to date and also prospectively looking at what the clinical data may look like. And I mentioned the satellite cell. So let's spend a minute on this. So the satellite cell uptake is something that is highly differentiated for Entrada. And what that allows us to do, at the end of the day, it really doesn't matter how much dystrophin you can make. If it does not translate to functional benefit, then it doesn't benefit the child or the young man.
And so at the end of the day, the ability to get into the satellite cells, which essentially are a cause for regeneration, will allow us to utilize the satellite cell data to regenerate muscle fibers that will then ultimately help with functional benefit. And this is something that we've proven not only in this slide here, but we're also starting to see in preclinical models as well. So a very, very exciting differentiating characteristic between us and the other approaches. We conducted a healthy normal volunteer study in the U.K. And this study was not only compelling, but it resulted in exactly what we wanted it to do. We wanted to run this study in healthy normal volunteers to de-risk the program. We had a lot of preclinical data, not only within different mouse models, but also with the non-human primates.
We wanted to, before we injected into a child or a young man, we wanted to make sure that the PK and the safety characteristics read out the way that we wanted them, too. And I'm pleased to say that this was a very important study that allowed us to achieve a couple of things. First and foremost, safety. You could see by the purple box on the bottom that there was absolutely zero treatment-related adverse events. That's super important, of course. Safety is paramount. What we were also able to show within these 32 adults was target engagement, the ability to not only generate exon skipping, but more importantly, the ability to get to the muscle, showing concentrations in the muscle. It's the right recipe before you go into patients. It's safe. It gets to the muscle, and it promotes exon skipping, which happens in the nucleus.
That was really what an aha moment for us to say, "All right, let's go all in here, and let's go straight into patients," which is what we are doing right now. Importantly, this safety and this study showed strong clinical safety up to 6 mg/kg, which is the starting dose of the patient study that I'll talk you through in a few minutes. The translation, ultimately, of non-clinical data to the Phase 1 healthy normal volunteer data establishes the potential of our DMD therapy. On this slide, what you see here within the healthy normal volunteer study is a dose - go left to right - is a dose response from a plasma concentration perspective. You could see as the dose goes up, so does the plasma concentration.
In the middle, you also see the same thing between 3 mg / kg and six mg per kg, a dose response where the skeletal muscle concentration also increases, and then, of course, from an exon skipping perspective, there is no dystrophin production, of course, because these are healthy normal volunteers who already have dystrophin, but these were three very, very important factors. The dose response becomes extremely important when we start to think of what the therapeutic index looks like. We spent some time, DMD is a very competitive space, as is neuromuscular, and so we spent some time putting together a slide that essentially says, "What are the differences between Entrada and some of the other approaches here?", and what you can see here, and I'm not going to read all this, but this trends well based upon everything that we've been able to see.
From the design, from the dose, and from the uptake and the target engagement, what we've been able to see is that not only does the 25-fold improvement in endosomal escape lead to better data, but it leads to a lower whole drug requirement when we compare it to these antibody-delivered therapeutics. There's a lot on the slide. What we wanted to do is put this together. This is preclinical and clinical data. On the left, we decided to do a study to compare ourselves to the published data that Avidity presented regarding their del-zota 44 program. What we were able to see on the left side of the first chart was two weeks post-dose, green is Entrada. The gray is del-zota. You could see the profound difference between the skeletal muscle and then, of course, the difference between us and the heart.
Then you go four weeks, and you see a similar thing. What's important here is, at the end of the day, this is 6 mg/kg for Entrada. So 5 mg/kg is the oligonucleotide. 1 mg/kg is the EEV. When you compare that to del-zota's 5 mg/kg, that's 5 mg/kg for the oligo, not including the antibody. So the whole drug size, when you want to do an apples-to-apples comparison between the two companies, we are one-sixth of their dose. One-sixth of their dose leads to this type of data. This is why we get excited about these data. This is why we get excited about Entrada, the ability to deliver higher concentrations at lower doses. And so that's what gets us really excited. The middle slide or the middle chart shows a non-linear dose response.
So this is from 10 mg/kg to 40 mg/kg. What you can see is at 10 mg/kg to 20 mg/kg, you see a difference of doubling from 5% to 10%. But this is the hockey stick type of advance. So you see a 3x greater muscle concentration, ultimately. And so this is what we expect. Our first dose in our 44 program is at 6 mg/kg. The second is at 12 mg/kg. The third is at 18 mg/kg. We expect to see this hockey stick type of reaction to dystrophin production. The third part of this slide, oligonucleotides, neuromuscular-focused oligonucleotides have had their liability has been to the kidney. The ability to get to the muscle is great, but not at the cost of the kidney.
What we have been able to see here on this analysis here is that for every doubling of our dose, we've been able to see a more than doubling of the metabolite excretion, which means that we double the dose, more stuff. I'll put it in air quotes, "gets out." So we are limiting the liability to the kidney. What this may imply is the potential to increase efficacy without a proportional risk of increasing toxicity. That is a very, very important point here, and it's a very compelling point for Entrada. The ability to get out of the kidney, the ability to not cause damage to the kidney, is something we've seen not only in our preclinical models, but we've also seen that in our healthy normal volunteer study. No effect to the kidney.
That's a big, big, big takeaway for oligos and a big advancement within DMD and DM1. This is the study. This is our ELEVATE 44-201 clinical study. It's designed to support a U.S. accelerated approval and form the basis of a global registrational program. If you look at this, there are three cohorts, as I said. The first cohort is 6 mg/kg. The second is up to 12, and the third is up to 18, a very wide therapeutic window. There are eight patients in this, six on drug, two on placebo. I'm pleased to report, if you look at the middle where it says double-blind period, that is concluded for all the patients. Each patient has been dosed, three doses, and they've all entered the open label period.
So now we're at that point where we are waiting for the data, which we will then present in Q2 of this year. This will be very similar. It's a very similar design for the 44 program as is the 45 program. So it's a little bit of a rinse and repeat. The 45 program has a little bit of a lower dose, so it's five, 10, and 15. But what I will say is the 44 program goes straight up against del-zota, and that's our plan is to beat those data. The 45 program goes straight up against casimersen. Casimersen has roughly 1% dystrophin production. We think we can comfortably beat 1% dystrophin. Now, that allows us to say we can go after these two exons. Oh, boy, we can go after 50, 51, and 53 as well.
It's the basis for Entrada to be a leader within the DMD space. This slide shows our timelines and our regulatory. I'm not going to focus on that because we've already shared it. I'll focus on the left side. When we think about the 44, 45, 50, and 51 exons, that's over 14,000 patients in the U.S. and Europe. That's a substantial opportunity. That's a substantial amount of patients who do not have an adequate therapeutic option when it comes to treating their disease. We also believe that if this data that we believe will translate to more than positive, we feel as though that the conversion or the adoption will be heavily weighted towards Entrada. This supports, in our belief, based upon really high-quality data, the ability to be the leader, not a leader, but the leader within DMD.
Let's move over to myotonic dystrophy type 1, our partner program with Vertex. So there's a pretty significant materiality wall between the two companies. We did this program. We established this partnership two years ago. Actually, sorry, three years ago now, Entrada received for a preclinical asset $224 million upfront and a $26 million equity investment by Vertex. And then there was $485 million of milestones. So a very significant single-asset preclinical deal. We feel as though the DM1 space is getting, of course, a lot of interest. And we feel as though there's a significant differentiation for our VX-670 program compared to the antibody-based approaches. And specifically, what that distinction is, is a very unique, and I'll use specific again, blocking of the pathogenic CUG repeats.
This targeted approach to be able to block the mutant DMPK is very different than our competitors' views as to how they block essentially indiscriminately DMPK. We think that this targeted approach will lead to a better outcome, and we're starting to see that. I think the other differentiating characteristic is what I was talking about with satellite cells. The satellite cell uptake may also increase the differentiation when we start to think of functional data as well. Vertex is advancing this program. As I said earlier, they are planning on finishing up this MAD from a dosing and enrollment perspective mid-2026. They have over 25 global sites initiated. The open label extension is enrolling. I feel as though they are going all in here. They've been spending a lot of time on this, and they highlighted it during their presentation as well, too.
This is, once again, a disease that has over 110,000 patients. It's a big one. I think we have a really, really good opportunity here led by our colleagues at Vertex. I'll move over to inherited retinal diseases, which we announced this weekend. Once again, this takes a similar strategy that we took with DMD. We looked at this from a top-down perspective. What are diseases that have a profound unmet clinical need? Then from a bottom-up perspective, what are we good at? The link here is that we're going after Usher syndrome type 2A, which has mutations in exon 13. It's an exon skipping type of approach. We've already proven that or proving that within our DMD and DM1 programs, and now we're moving that over to Usher.
What I like about this as well, too, is that this is a large disease. We're talking about 15,000 patients across the U.S. and Europe and probably even more that we can potentially address who do not have any therapeutic options. And so for us, when we start to think about where else is Entrada going to grow besides DMD and perhaps DM1, this is our next big pillar. And so we're really excited about this. We'll share more about our clinical plans and whatnot as the year progresses. But this is our first one. So we announced this one. We're going to announce another clinical candidate in 2026 for inherited retinal diseases as well, too. So we've put our flag, so to speak, in the ground here when it comes to oculars. I'll reemphasize that there's no disease-modifying treatments for Usher syndrome type 2A.
We're really excited about the ability to go after this on behalf of the patients. The data here, we'll share a little bit of data here. But what we've shown in this slide is a single IVT dose of ENTR-801 reaches the exon skipping target that we hear from KOLs is clinically relevant. We've also been able to generate a protein that's measurable for at least 90 days, which shares the potential for a dosing of one to every two to three months. We're excited about the fact that at this early stage in this program, we've been able to achieve that clinically relevant exon skipping of above 25%, but at the same time, have a potential dosing regimen which will be advantageous to the patients. More to come here, but a very exciting start to our ocular programs. I think that's that. And then pipeline expansion.
So as I said in the beginning of this presentation, when you go after these intracellular targets, there are plenty of them to go after. We can't go after all of them, of course, but the flexibility and modularity of our approaches lends well to exploring other therapeutic areas as well, too. So what we are working on back in our Boston labs is more complementary modalities to go after diseases of interest, including next-generation EEVs to continue to advance the TI and also increase efficacy, continuing to optimize oligonucleotides so that we can develop proprietary sequences not only from an IP perspective, but also from an enhanced safety and efficacy perspective with and without EEVs. Also, a protein engineering group, which is just probably the best out there that is working on improving not only potency, but efficacy and bioavailability.
So what we see specifically is we will continue to expand in neuromuscular. That is something that is dear to us and something that we're good at. And so we will continue to seek out and share news about other diseases we're going after. As I said in the previous slides, we will also continue to expand our ocular franchise. We're starting with Usher, and we will expand out of that into other inherited retinal diseases and perhaps diseases that are larger and broader within the ocular. And then, of course, there's a whole host of undisclosed diseases that we're looking at metabolic diseases. We're looking at CNS. We're looking at a bunch of others as well, too. So in summary, 2026 has a lot of catalysts. We've talked about our ENTR-601-44 program, first catalyst. First clinical data will be Q2.
Second clinical data will be end of year. Our 45 program continues to go well. That data, first cohort, will be shared in the middle of this year. Our 50 program is going through the regulatory process, and we'll start to initiate that by the end of the year, before the end of the year, then 51 as well. VX-670, that's under great leadership with the Vertex team, and they expect to finish enrollment and dosing in the middle of this year and hopefully sharing data soon thereafter. Our newest entry into ocular, where we've announced the candidate for our Usher program, and we'll continue to expand about that. And then also a significant round of pipeline expansion. Entrada is here to build the next best standalone intracellular therapeutics company.
We're excited that we still have a lot of cash to achieve all these goals, but obviously, we're going to have to invest more into the company. But the current cash runway goes into Q3 of 2027, so well capitalized for now to achieve a lot of these milestones. With that said, please go to our website to learn more, but open to Q&A. And Natarajan's up here as well, too, as our President of R&D, to answer any questions that anybody may have. I think we have about 10 minutes. All right. You have a question? All right, go ahead.
Yeah.
This is Han. Okay, yes. So to kick off the Q&A, could you talk a bit more about how this first cohort from the ENTR-601-44 study will de-risk your other Duchenne programs?
Yeah. So as I said, first and foremost, it's the same EEV across all the DMD programs. So that's half of it. So you got the EEV, and then you got the oligonucleotide or the proprietary oligonucleotide. And so we feel as though that this first the approaches are all the same. We feel as though this first cohort of data sets up that positive domino effect. So 44 data should translate well to 45 data to 50 data to 51 data. I will caveat that by saying that these are all under the DMD landscape. We view these as individual diseases, but they have a tight correlation between them. But I think the similar EEV or the same EEV coupled with a PK that we understand really, really well is how we view de-risking future not only future cohorts, but future programs for DMD.
Awesome. Thank you. Any other questions from the audience?