Conference Transcript - TRDA 2026-11-09

Devjet, Host

Joining me for the first afternoon session is Dupal Doshi, CEO of Enterada Therapeutics. Dupal, thanks so much. Thanks, Devjet. So, you know, for folks who might be new to your Enterada story. Could you give us a very quick overview before we get into the pipeline questions?

Dipal Doshi, CEO

Intrada is fundamentally based on a family of cyclic cell penetrating peptides, which we've named endosomal escape vehicles or EEVs. So it started as a delivery mechanism company, and then of course it evolved into a therapeutics company. And 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 through from an intracellular perspective. And so 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. And so 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 Myatomic Dystrophy Type 1. So I'll pause there.

Devjet, Host

Awesome. So obviously, 26 has been a challenging year for the company, but you are heading into what could be a momentous year if everything works out. Could you just lay out what we should expect from the different programs? Sure.

Dipal Doshi, CEO

Yeah, 2026. It 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 1-2 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 has 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. So the first one will be our Cohort 1 open label data release for our 44 program. And so that we will see before the end of the year. Before the end of this year. And 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. And so 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 mix per kick, so double the initial one. And then our third will be before the end of the first half of 2027, and that'll be the second cohort of our 45 program. So a tremendous amount of value that could be generated over the next six to nine months for the company.

Devjet, Host

So the Exxon45, the low-dose, 5-mix per gig data were disclosed recently. From our side, it was mostly a safety update because of the obvious challenges translating the annual model to humans. What would you think or what would you say investors should take away from that? Sure, yeah.

Dipal Doshi, CEO

Well, first and foremost, I would start with the unmet clinical need, right? So 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 Casimirson or Amandus 45, which generates over $300 million in sales a year. So 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, you know, it's two parts of a puzzle, right, safety and then efficacy. And we established that with that five mix per kg dose. Now, these patients in the trial were quite young, roughly around six to seven years of age. And so they're continuing to do well until the disease starts to take over. So we did not expect a lot of dystrophin to be produced for these patients. Mind you, Casimersin is at 30 mg per kg, and it's dosed every week. For Entrada's 45 program, we're looking at, you know, currently it's one-sixth of the dose, but it's going to be dosed every six weeks. So there's a huge, huge, you know, 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 PKPD 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. So 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.

Devjet, Host

So the 10 mg per kg cohort is fully enrolled. Where do you think the dystrophin expression data are going to fall in your sort of inflection curve as you go up the dose?

Dipal Doshi, CEO

It's a good question. We haven't guided towards our expectations for cohort two, but what I will say is there's likely going to be three cohorts pending what cohort two looks like. So the third cohort would be at 15 mg per kg. Somewhere between 10 and 15 mg per kg, I think we're going to start to see a significant dose response. We feel as though if it's a linear response, that could result in cohort two being just a little bit more. But we feel as though there's this hockey stick that happens with dystrophin, and we're on the cusp of that. So we would not be surprised if we see a significantly higher amount of dystrophin within cohort two compared to cohort one. But we'll see.

Devjet, Host

And where does cohort 3 fit in? I mean, from a therapeutic window perspective, this is actually a slightly lower dose than the exon. 44 program? Yeah. Where you're 6, 12, and 18. Correct. Here you're 5, 10, hopefully 15. Hopefully 15, yeah. So first of all, can you walk me through the choice of the dose here and then talk about the safety of the, or how you think the therapeutic window is? Yeah.

Dipal Doshi, CEO

44 and 45 are very different. We kind of characterize them as different diseases under the DMD umbrella. They're all severe, of course, but, you know, 45 has no therapeutic options. But what we were able to see in our cohort one was we saw older patients. Mind you, like, you know, 10 to 12 years of age, roughly, and they also had higher baselines. And so when we juxtapose that to the 45 patients, which were younger, with very little or very low dystrophin, they kind of present as two different diseases. The dosing was really based upon just preclinical in terms of the exposures that we saw. There's really not a huge difference within the dosing. It's just really based upon NHP exposures and whatnot. But what we expect for both of these drugs or potential drugs in the cohort two is a significant response. Dystrophin is important for the U.S. pathway for accelerated approval. That's the importance of dystrophin. It's a good biomarker, but the relationship between dystrophin and functional endpoints is emerging. For us, it's important to get dystrophin up because we want to get accelerated approval in the U.S. for 44 and 45. For the patient, it's more important to get functional benefit and safety. So we have the ability to do all three, have safety, have higher dystrophin, and also have a continued functional benefit, and that's what we hope to see in 2027.

Devjet, Host

So let's unpack that a little bit. So in terms of. Just for an expression, what do you think the level is? One for accelerated approval. And two, the inflection point where you start seeing a functional benefit in these patients.

Dipal Doshi, CEO

Yeah, it's a hard question to answer, and I think part of that is because Intrada's approach is quite unique. We have the ability to not only get to the damaged muscle, but we believe we have the ability to get to the satellite cells. And we think that that's what drove our ability to get functional benefit measured by time to rise and time to rise velocity in our first cohort of 44 patients at a low dystrophin production. You know, the market was very unforgiving to us. And that's, you know, that's OK. It is what it is. But at the end of the day, we showed functional benefit at a very, very small dose or low dose. And we believe with low dystrophin, and we believe that's because of the ability to get to these quiescent satellite cells. We'll see if that continues. It's a hypothesis that we're doing more work on, but we'll see if that continues into cohort two. The same, I think, applies for the 45 drug as well, too. So it's kind of hard to say what dystrophin level we need to achieve more profound functional benefit because we're already seeing it at low levels. I think for us, once again, dystrophin becomes a very important tool for accelerated approval. We believe that we will see continued functional benefit most likely in the open-label studies because that's a larger duration of time versus the MAD studies, the multiple ascending dose studies, which are really only three doses. I think the more doses you get, especially within ENTR 601, 44, and 45, the dystrophin builds up and hopefully will translate into functional benefit.

Devjet, Host

So how do you think the agency is likely to evaluate open-level data in What are otherwise sort of effort-mediated tests, right? What kind of validity is and are buried in those data? Yeah, it's a good question.

Dipal Doshi, CEO

I think it's a two-part answer, the agency in the U.S. and then the regulatory agencies outside. So in the U.S., the agency wants to see a statistically significant difference in dystrophin. I think that becomes the most important biomarker to be able to achieve accelerated approval. I think functional benefit is important from the agency's perspective because they want the drugs to not only be safe, but of course they want them to work. But dystrophin expression is the most important thing within the U.S. Ex-US, where our trials are being currently run, is a different ballgame, right? The biomarker is less important. The functional benefit is more important. So I think that's what gives us a good feel or an optimistic view in terms of our regulatory pathway because we're looking for global approvals. And in the US, we believe as though the dose response will lead to a statistically significant change in dystrophin. And then ex-US, we believe that that functional benefit will continue within 44 and hopefully within 45 as the time goes by. So I think that's kind of how we view it.

Devjet, Host

So, from our channel checks and talking to your competitors, it seems like 90-plus percent of the patients who are on the current exonskipping drugs are home administered, and they don't see their physicians that often. So, if you were to go forward with accelerated approval, what level of dystrophin would you need to get a switch from... Sort of an entrenched market.

Dipal Doshi, CEO

Yeah, I don't think it's the dystrophin. I don't think the patients are as concerned around their dystrophin levels as they are concerned about their ability to live their lives, and I think that comes down to the convenience of dosing, right? So when you start to think about this, every week, whether it's home or they have to drive somewhere, their mom or dad or caretaker has to drive somewhere, they're infused for one to two hours every single week at 30 mg per kg with Kazimierzon. I can only refer to 45 because 44 doesn't have anything right now. Now, if you juxtapose that to what Entrada already has, right, we can bring them to, of course, we can do home infusion. That's just an expense perspective. But the convenience of dosing is such a big deal, especially for young kids who, you know, their parents or their caretakers want them to have the most active life that they possibly can have. And so to go every six weeks to get roughly over the course of a year to get eight to nine doses versus 50 to 52 doses, it's a big, big, big, big difference. And I think for us, I think that's a huge value proposition when we talk to the patient communities, when we talk to the physicians as well, that comfort and that ease of dosing is a big deal. And so to answer your question directly, once again, I don't think the patients care about the dystrophin. I think they care about safety and they care about functional benefit. Am I able to get up faster? Am I able to use my arms? Am I able to do the things that, you know, healthy, healthy, otherwise healthy patients can do? That's what we're looking for. We're looking to hopefully make their lives better from a functional perspective.

Devjet, Host

So, let's take a break from talking about individual exons and talk about your platform. What sets the... Entrada delivery approach for oligonucleotides different from what's being pursued everywhere else.

Dipal Doshi, CEO

Yeah, I think it first and foremost starts with safety, right? So we've been able to establish safety both in DM1 per Vertex's comments and in DMD, and that is utilizing the same EEV across three different programs, VX670, Elevate44, and Elevate45. So I think it starts with safety. We've seen some competitor data around infusion-related side effects dropping out of DMD studies because of safety. We, fortunately, have not had anyone drop out of any of our studies. So I think it starts with safety. I think what also makes us different is that dosing as well, especially when it comes to 45. I think there's so much translation. We've been at this for a while now. What we're seeing are consistent metrics in that we're seeing the safety, we're seeing the ease of dosing, we're seeing the exposure levels be very consistent as well, too. I think it's hard to interpret some of our direct competitors' data outside of Sarepta, right, because they've been around for a long time. But to evaluate Avidity or Novartis' Delzota data is a little bit more difficult because they weren't able to get that dose response for their 44 program, and they had a couple patients drop out as well, too. So I think there's some of that from a translation perspective. I think the last thing I will say is the drug size, right? So when we think of our first cohort, so now I'll compare Entrada to Novartis Avidity, our six mgs per kg is five mgs per kg of the oligo and one mgs per kg of the EEV. That is almost one-fifth of their total drug size. It's a big difference when you're a small kid. Within our 45 program, our five mgs per kg is compared to Sarepta's 30 mgs per kg. That's one-sixth. Right? That's a big difference when you're a little kid. The amount of drug that you're giving and the fact that the EEV controls the PK is a big deal when we start to think about targeted therapeutics. And I think that's what gives us a lot of confidence within what the end game here is, which is to get a differentiated drug approved for these diseases.

Devjet, Host

Got it. So now that you have dozed... More than a handful of patients on Exxon 44 at the higher 12 mic per gig dose, and you've completed enrollment in the... 10 mcbrick egg dose with Exxon 45. The safety profile that you've seen at the lower doses, does it still hold up?

Dipal Doshi, CEO

It does. I mean, I think at the end of the day, what we've seen in 44 is a very translatable safety. You know, 45, also we've had some, you know, we've had some treatment. Of course, we've had some T treatment emergent adverse effects. But once again, I think the importance is that the totality of the data allows for the comment to be made that no one has left the study. And no one has dropped out of the study, which is not something that a lot of these competitors, you know, can say, and that becomes important. So the promise and the efficacy of the drug outweighs the safety liabilities, which we're fortunate to say we don't have. We hope that continues. Remember, these are very, especially with 45, these are patients that don't have a lot of dystrophin already. So we're actually, in some regards, You know, putting something new into their system, and we expect to have, you know, the body to react in a certain way, but we've been very fortunate. What I will say is the kidney is the organ of liability when it comes to conventional DMD. We don't see that. We haven't seen any material renal effects of negativity within our studies, and I think that's a big, big, big deal.

Devjet, Host

Got it. I want to jump to the Vertex partnership and the DM1 program before we close off the loop with X144. Can you sort of remind us that partnership, if I'm not mistaken, was like $468-ish million?

Dipal Doshi, CEO

Yeah, so the upfront was $250 million. Remember, this was a preclinical asset at the time. So the upfront was $250 million, and the milestones were up to $485 million, and then there was royalties that are associated with it.

Devjet, Host

So if Vertex decides to advance the program into registration study, is there an immediate impact to you guys financially?

Dipal Doshi, CEO

So we, from a milestone perspective, we're... Unfortunately, contractually obligated to not disclose those milestones, but the way that I would view it is that the probability of success around those $485 million of milestones or the POS goes up substantially. So I think that's a big deal, right? Importantly, in our current runway, we don't include any of the milestones that can be achieved through this vertex collaboration. So the runway is actually very, very clean and doesn't include any of that upside.

Devjet, Host

Got it. So, with the data... Within the next month and a half-ish, what do you think should the investor expectations be? We know the safety, but your partner has commented on that publicly, but where do you think efficacy should line up, given at least the preclinical data that you might have access to?

Dipal Doshi, CEO

Yeah, I think, you know, once again, we are blinded to these data based upon the strict firewall up between the two companies. But our expectations, our hope, is that they continue to see the splicing that we saw pre-clinically. I think that is an important factor here as well, too. As we talked about extensively, safety's been established. So this next part would be, what does splice-opathy look like at the doses that they're running? I think that's something that we're keenly interested in. And then ultimately comes down to functional benefit, right? And so obviously there's been a failure in the field with Avidity's program around VHOT. I think the important thing for Vertex that they disclosed are looking at multiple different functional endpoints, including VHOT. So we'll see how that all unveils. I think importantly, we want to see, obviously, safety, and we want to be able to see splicing, and then we'll go from there.

Devjet, Host

Got it. Okay, so with the Exxon 44 program, the bar is pretty high, right? Novartis Avidity, you're talking about a mid-40%, not baseline adjusted, but mid-40% kind of expression. So what gives you the confidence that you can get to that level, and do you have to necessarily beat that level to make this program viable?

Dipal Doshi, CEO

It's a good question, and I think a lot of that will hopefully be understood and probably further complicated when we release our open-label data, when we achieve it. If the open-label data for 44 Cohort 1, once again, the lowest dose, shows an ability to stabilize the disease, remember, these kids will have been on drug for about a year. We expect them to decline without any therapeutic intervention. If we're able to show a betterment of disease or a stabilization of disease at that low dose, at that minimal dystrophin level, this will throw a fair amount of questions around how important is dystrophin from a functional benefit perspective. I think for us, the field is wide open for 44. I don't think enough is understood yet as well, right? I think if you're able to get a drug approved or through clinical trials that has a lower dose, that has a competitive functional benefit perspective or readout, I mean, there's always room for more than one. And I think for us, I think what we haven't seen longer term is some of the issues that DelZota has seen in the short term, which is infusion-related side effects. Like, we've been fortunate not to be able to see that. We haven't had a single kid drop out of the clinical studies at the low dose or even at the 12 mix per kid dose as well, too. So I think we have a lot of room here to create not a competitive drug, but a better drug.

Devjet, Host

So the open-label data from the low-dose cohort are expected sometime over the near future. If you continue to see a functional benefit that goes above and beyond what is expected from natural history, The underlying mechanistic rationale of hitting muscle stem cells, how does that fit into the story?

Dipal Doshi, CEO

Yeah, it brings it into light in a big way, because what it will do is it will draw into question the one-to-one relationship between dystrophin and functional benefit. I think for us, I think it will say, it will probably prove out a hypothesis that we do believe, and we've seen this preclinically, But it will prove out clinically that there's something going on with a two-pronged approach here, the ability to go to damaged muscle fibers that are in existence, but also to be able to see, hopefully, PMO within these satellite cells, and that's doing something for regeneration. I think that'll be a really interesting conversation to have once we disclose those data.

Devjet, Host

And could you just remind me the scope of the functional data that you plan to unveil? Does it have, say, for example, SV95C? It's a good question.

Dipal Doshi, CEO

Specifically for SV95C, it wasn't in the original protocol, but we do plan on measuring that in the expansion cohorts. But other than that, NSAA, time to rise, pull, 10-meter walk, all the standard gold star measurements when we start to think of functional benefit.

Devjet, Host

Got it. And of those, obviously, time to rise is one of the more unfungible kind of endpoints. Do you want to put emphasis on time to rise? And I see 95C as the more, you know, endpoints that are probably more acceptable to regulators?

Dipal Doshi, CEO

Yeah, it's interesting because I still think the regulators spent a lot of time on NSAA as well, too, because NSAA is a compilation of 16 or 17 different functional measures, so it gives you the broadest, most viewed-upon representation of how the patient is... It's adjusting or reacting to the disease, but it's also the one that moves the least because it's a very difficult measure. So I think it's all of them. I think it's really all of them and contextualizing all of them at the same time. And we do know that these functional measures are strictly controlled in terms of how they are represented. But I think it's going to be interesting to see how NSAA moves, TTR moves, pole, and of course, 10-meter walk.

Devjet, Host

All right, so in the last 40 seconds or so, could you sort of- Where are you with your balance sheet? And, you know, given all these programs, all these updates, where do you plan to be end of the year? And is there any way to monetize the Vertex partnership so you don't have to dilute?

Dipal Doshi, CEO

The last question I'm not going to answer, but we have cash that goes into the Q4 of 2027. I think we have multiple ways to raise money. You know, obviously, a clock is ticking, but we're going to wait for these data. We've done a very good job of not diluting shareholders over the course of our four years of being public. We have not raised a lot of money, but we have the opportunity, based upon those four different milestones that are going to be achieved, to raise money. But I will answer. If the Vertex VX670 data looks good, that also gives us additional optionality as well, too. So, we know we have to raise money, and we will, based upon data, and, you know, we're hopeful that that data looks good.

Devjet, Host

Appreciate your time, Deepal. Thanks, man.