EyePoint, Inc. (EYPT) March 25, 2026 Conference Transcript

Good morning, everyone. I'm Lisa Walter, biotech analyst here at RBC Capital Markets. Thanks for joining us at RBC's Ophthalmology Conference. This session, we have Jay Duker, Managing Director and Chief Executive Officer, and George Elston, EVP and Chief Financial Officer from iPoint. Jay, George, thanks so much for joining us today. How are you both doing?

I'm doing great, Lisa. Thanks for having us. Yeah, things couldn't be better. Looking forward to the call.

Glad to hear it. And it's a pleasure to host you this morning. Well, team, maybe to kick things off, could you give us a big picture overview of the company and give us an idea of where things stand with the lead program, DuraVue, for retina diseases?

Happy to do so. So, Lisa, big picture, things could not be going better right now. As you mentioned, our lead asset is called DuraVue. It's a small molecule tyrosine kinase inhibitor called virolinib, which is in our DuraCert-E formulation. DuraVue is currently being tested in four ongoing phase 3 trials, two in wet age-related macular degeneration and two in diabetic macular edema. The wet AMD trials are called Lugano and Lucia, and the DME trials are called Como and Capri. We are highly confident in the results of these trials at this point for a lot of reasons, but I think most importantly, based on our robust phase two results. And just to review for a moment, our phase two wet AMD trial, which was called Davio-2, enrolled about 160 patients, all previously treated wet AMD patients. And they were randomized to either on-label control, which was ILEA, or one of two doses of DuraVue. The results were great. There was no significant difference in the final change in visual acuity between the DuraVue doses and ILEA. And therefore, there was a non-inferior result that was achieved. and non-inferiority change in visual acuity is the primary endpoint for our phase three trials as well. Beyond that, we really had terrific safety. And in the phase one trial and the three phase two trials that we've completed, we've dosed over 190 patients with Duravu, and we have no safety signals and no ocular or systemic SAEs that are attributable to our drug. So the safety really looks quite clean so far. The efficacy results beyond just non-inferiority. The eyes in the trial at primary endpoint gained about a letter, which is to be expected in a previously treated group. But if you break it down and look at the eyes that were not supplemented, in other words, they made it to the primary endpoint with DuraVue one dose alone or ILEA on label. The DuraVue doses both numerically actually did better than on label ILEA, an average of 2.1 letter improvement with DuraVue alone versus 1.7 letters for the control arm. So it actually showed that when our drug worked by itself in those eyes, those eyes did really, really well. There was a significant reduction in treatment burden the way it was measured, and that trial was about 80%, and about two-thirds of the eyes made it up to six months after Derviu went in without requiring any kind of supplement. And the other thing that was important to note is the anatomic control. We measure anatomy in the back of the eye using the OCT machine, and normal's about 300 microns, and the standard deviation's about 10 microns. And we were about standard deviation change in OCT, less than 10 microns in the higher dose and about 10 microns in the lower dose. And so the phase two trial was really encouraging. And there were a lot of learnings from phase two that we were able to apply to the phase three Lugano and Lucia program. And because of those learnings and because of the safety that the retina specialists saw, we were able to fully enroll both those trials in really record time. Each trial took about seven months to enroll. We enrolled about 432 patients in the first trial and about 475 in the second trial. And in that trial, they were randomized to either a single dose of DuraVue, 2.7 milligrams, or ILIA on-label control. And again, for a non-inferiority trial, the FDA really mandates that you use an on-label control of either Lucentis or 2-milligram ilea. So the trial's enrolled very rapidly and are moving along very well with respect to the WET-MD trials. We are dosing those trials to review every six months. And so at this point in both of the trials, Lugano and Lucia, all the patients have received their second dose of Duraview, and almost 50 percent have now received their third dose of Duraview. And as we've talked about, we are looking at the mass safety, and we do have a data safety monitoring committee. Last time they met, they recommended no changes in the protocol. And in fact, we've made no significant changes in the protocol for the phase three trials because of the learnings of the phase two, which is of course why you really do a phase two to de-risk your phase three. So we are really, again, optimistic about the way things are going and confident in the results in wet AMD. So we have the first readout for the Logano trial. The top line should be sometime around August of this year. So in approximately five months from now. Exciting news. We plan on reporting Lucia approximately two months later, depending again how that all goes. Retention in the trials has been terrific. We're about 5% of patients dropping out in Lugano and about 4% in Lucia. And standard is about 10% and wet MD trial over a year. And so we're doing really well with retention. So when we talk about the readout, I mean, obviously the primary endpoint is non-inferiority change in visual acuity in the 2.7 milligram dose versus the control. And I'd say it doesn't really matter what the actual change in vision is. I'd like to remind people that high-dose ilea, which is, you know, widely used by retina specialists, and it's a terrific drug, when they did their non-inferiority trial against 2-milligram myelia, it was 1.4 letters worse. So that 1.4 letters, that's not an amount of change in vision that is meaningful to doctors or patients. So as long as we hit the statistics, I think the actual value of change in vision probably isn't meaningful. But now I'm going to contradict myself because if we're actually like in our supplement free arm in phase two, if we're actually a little bit better vision, I think that would be very helpful to us from a commercial perspective. So we need to hit the primary endpoint, obviously. Safety, again, is equally important, and we have reasons to be quite encouraged about our safety, as I mentioned already. And then the final clinical aspect of things that we need to hit in the wet MD trial is reduction in treatment burden. Now, the way that's going to be measured in these trials is everybody gets loaded with ILEA three doses in the first eight weeks. So the treatment burden starts counting after the ILEA load. So in the first year of the trial, all the patients in the DuraVue arm will receive mandated two DuraVues, and all the patients in the ILEA arm will receive mandated five ILEAs. So if there are no supplements, then that would be a 60% reduction in treatment burden. Well, I'm sure there's going to be supplements probably in both arms because we have those in phase two in both arms. And so if we have supplements at the same level that we had in the phase two, we have about a 40% reduction in treatment burden, and we have reason to believe that we will have less supplements in the phase three than we had in the phase two. But even if it's 25%, 30%, that's going to be highly statistically superior. And so we're quite confident that if we hit non-inferiority, that third aspect, the reduction and treatment burden should be really easy to hit also. Now, if we hit that, the first two, we can go back and test for superiority in change in vision against the ILEA control without a penalty. So that's, again, a little preview about what we would expect to see at the top line this summer. If I may, I'll go on to DME.

Please, please do.

Okay. So we did a phase two DME trial called the Verona trial, and that was actually the first time that we tested our higher payload inserts. The payload of the inserts that we had prior were either 400 micrograms or about one milligram, but our scientists were able to increase the payload to 94% drug, only 6% matrix, without any changes in the release and in the biorodibility. And we tested those in Verona, and the inserts performed great and in fact one of the big findings in the Verona trial is head-to-head against ILEA in active DME patients meaning they had fluid they had decreased vision as early as week four we had four to five letters better vision in our treatment arm than ILEA and we were about 50 microns thinner so our drug worked fast and it actually worked better than ILEA did in the short term. Now, if you think about that and say, okay, let's suppose you're non-inferior to ILEA and you end up with the same vision at the primary endpoint, which is a year. If we can show that at week four, we get better vision faster, even if we end up the same, I think we're going to have a huge portion of the DME market because who wouldn't want to get their vision back faster and have less fluid in their retina with fewer injections. I think that would be obviously really a huge win for us. So Combo and Capri are identical trials. They're each going to enroll about 240 patients. They're both in the U.S. and ex-U.S. sites, and they're both up and running recruiting patients as we speak. And we expect to announce full enrollment in Q3 of this year, which would put us top line results in Q4 of 27 in DME.

Got it. Thanks for that overview, Jay. I think you answered a lot of questions that I had. I just wanted to ask, there was an announcement last Friday after the close. I was wondering if you wanted the opportunity to comment on that.

Sure. I'm happy to address the issue, Lisa. So as I just indicated, you know, DuraVue has really benefited from a de-risked standard, I would say, drug development program, including a phase one trial and three phase two trials dosing over 190 patients that have been reported. So as I mentioned, we use those results and learnings to inform our phase three trials that are ongoing. Duraview's efficacy and safety profile is well established in those 190 plus patients. And again, just to reiterate, no safety signals, no Duraview related ocular or systemic SAEs. Unfortunately, the Duraview data, which has been publicly available for a while, has been misrepresented and falsely portrayed by a competitor. We had multiple attempts to resolve this directly with the competitor, but they were unwilling to do so. And that really left us with no choice but to pursue legal action. It's really unfortunate, but we felt it was a necessary step. We're insistent on continuing the development of the review in a fair setting, letting the full data set speak for itself. So our main priority with this action is to correct and remove the false statements and to ensure this doesn't happen again. We are completely committed to the retinal disease patients we aim to serve through our programs, and we can reassure everybody that this action is not going to distract us from our focus on continued exceptional clinical execution of those phase three programs that I just talked about. Uh, so given that it is an ongoing legal matter, really can't comment further, but I hope that explanation is enough to, uh, to, to, uh, inform you and the listeners as to why we felt we had to take this action.

Got it. No, thank you, Jay, for that. That's really helpful. Um, I just want to touch on a few things in, in your, uh, opening remarks here. And so did you say almost 50% of patients now have had a third dose of DERVU. Is that across Lugano and Lucia?

That's in Lugano. Lucia, again, is, you know, started about two months later. And so some of the patients have received their third dose, but actually don't know the actual percentage.

Got it. Okay. Okay. That's helpful. And I do want to talk about the non-inferiority endpoint. You know, in the U.S., it's pretty well established. It's in the guidelines from the FDA that they want to see a negative 4.5 delta minimum. But I'm just wondering, ex-US, the non-inferiority margin is a little bit tighter, correct?

I think it has been historically, though we asked for a 4.5 non-inferiority margin in Europe as well. And so I think the things do evolve and things change based on evidence. And so and just to say the DME trial in the U.S., we were also granted the 4.5 non-inferiori margin. And that has been 4.0 for some programs in the past. So things obviously at the FDA and EMA do evolve over time.

Got it. OK, that's helpful. Um, maybe let's just talk a little bit about, uh, Lugano, Lucia and, um, you know, the primary endpoint is very clear what, what you need to do there. Um, you also mentioned you don't necessarily need to have a positive gain in BCVA. You just need to hit the margins, but it would be nice commercially if you, you did have a positive gain.

Well, I, I, I think to be clear for us to hit the non-inferiority margin, we would need a positive gain in vision. So we remember it's change in vision from day one at randomization in the two groups comparable. So if you ask the question, what would the change in vision in the ILEA control group look like? Well, I think you can kind of figure it out fairly easily. Just look at the control groups in the last couple of approved products for bismil and high-dose ILEA, And in those cases in WetMD, you had about a five-letter improvement in the control. But remember, we're 75% naive, 25% previously treated. And you can go back to our previously treated data from DAVIO2 and notice that there was about a one-letter gain. I mentioned that already. So you can kind of put that together and figure out approximately where one would expect the control group to do. So given that, and given the non-inferiority margin in the end of the trial and the standard deviation, we would expect that in order to be non-inferior, DuraVue would need a positive gain in vision also. Now, when you talk about the difference, however, as I think I said already, if we were only 0.3 and 0.4 letters worse than ILEA, which statistically was identical in DAVIO2, That would be obviously an outstanding result. But I mentioned already, clearly the market has spoken with high-dose ilea. 1.4 letters worse is fine. And if it's non-inferior statistically, then there's no problem with that result. But that would still likely leave us with a positive outcome. And remember, again, every wet AMD drug that's been approved in the last six or so have resulted in positive visual acuity changes at the primary endpoint. So we would expect a positive change for us, too, if we hit the primary endpoint.

Got it. So a positive BCVA change overall, but the delta between a flibricept and a DuraVue doesn't necessarily have to be a positive gain. Correct. Correct. Got it. Got it. Well, let's just touch on the secondary endpoint or one of the key secondary endpoints, the reduction in treatment burden. You already touched on this, but is a reduction in treatment for injections, is this calculated just by the number of supplemental injections or the total injections patients are getting?

So it's a good question, Lisa. It's actually both the mandated injections, which as I indicated in the Derviu arm will be mandated two injections over the efficacy part of the study, and five ILEAs mandated. You add on the supplements, and again, we do expect to be supplements in both arms. Remember in Davio 2, it was a tough-to-treat group. And one of the pieces of evidence for that is the control arm, despite getting every other month ilea after a load, 6% still got a supplement at the primary endpoint. And at one year, 13% got a supplement. So even though they were getting every other month ilea, they met the requirement for supplements there. And in fact, if you go back and ask the question in this tough to treat group, at any point, how many eyes in the ilea arm met supplement criteria, it was over a third despite getting every other month ILEA. So that indicates this was a tough-to-treat group. So back to how we calculated, again, it's the supplements plus the mandated up to week 52. At week 56, it's going to be both a mandated redosing of DuraVue and a mandated redosing of ILEA at that visit. So if you've got a mandated injection, it doesn't count as a supplement. But the statistics on this is we need to show statistical superiority. And when you run the numbers, you know, the end of the study is really high. There are about 450 patients approximately in each arm. And so we will only have to show like a 7% or 8% reduction in treatment burden to be statistically superior. Now, we fully expect to have much lower treatment burden than that. And we really need to, to hit our primary endpoint. But my point again, is if we hit the primary endpoint statistically, that secondary endpoint is pretty much going to be hard to miss.

Got it. And maybe just to understand this a little bit more. So DuraVue is dosed at week eight in the study. And you just said that the injections that are going to be counted as part of the treatment burden are going to be the supplemented and mandated ejections up to week 52. So we should be trying to look at the reduction in treatment burden from week eight to week 52. Is that the right way to think about it?

That's correct. But at the week eight, the ILEA arm gets a mandated ILEA, which is part of the load. So that one doesn't count. But the DuraVue gets the first DuraVue. That one does count. got it okay two total de reviews five total ideas is is how it's going to get calculated plus the supplements okay that's i think that's helpful for for us uh us to understand yeah and and i do want to add it's it's very much different the way we count than what we calculated in the phase two and what other companies have have have reported uh and so that you know it's physically impossible to show anything better than a 60% reduction. But as I said already, a 40% reduction would be outstanding, provided we hit the primary.

Did you align with the FDA on what a meaningful reduction burden percentage would be, or it just needs to be statistically significant?

Well, no, and there's no alignment there. I think that what we talked about, again, is statistical superiority in treatment burden and less treatment burden. So the actual number of supplements, there was no cutoff. That was never discussed. And I would think that that probably has been true in all the discussions because this is also, it's a totality of data. It's safety and efficacy. And so I think you can't just isolate one finding without knowing the change in visual acuity and how safe your drug is to make an assessment of what was the supplement rate acceptable or not acceptable. And there's sensitivity analyses that go into that as well that obviously will be performed.

Do you think the 40% number is the bogey that the investment community wants to see? Is that what you want to see?

No, I don't think so. I think the number could be much less than that, and the KOLs would be happy with it. Because remember, supplements in the real world are not a failure. it's a that's a really important concept because this the the the idea behind sustained release and our drug in particular is that we're working with the uh historical biologics in fact every patient in the study gets loaded with ilea and gets some potentially will get supplemented with ilea so it's not an either or and you know the the the good example here is if i'm treating a patient and I have to give them ILEA six times a year to keep them under control. And let's suppose Duraview is now approved and available every six months. And I give this patient two Duraviews over the next year, but I actually also give them two ILEAs. Well, everything's happy. Everyone's happy. The patient's gone from six injections to four. The doctor is able to now spread out the injections. And remember, this is a different MOA. And wet AMD is one of the few chronic diseases that's only been treated with one MOA. I think there's evidence that treating with two MOAs here may actually give better results. And ultimately, this isn't about reduction in treatment burden. This is about better visual acuity in the long term. The compliance that is automatic when you give a sustained release to a patient, we believe in the long term would result in better vision. So again, I don't think there should be a necessary fixation on precise numbers of reduction in treatment burden or number of unsupplemented patients, because in the real world, as long as we're getting the visions we want to get in the anatomic control, and we can do it with fewer injections, supplements aren't really going to be an issue.

Got it. That's helpful, Jay. Well, I do want to touch on the safety profile that we've seen to date. But one thing I do want to ask is, I know in Davio 2, some patients did get a aqueous humor tap, which makes sense to measure PK, PD, that kind of thing. I was wondering if that is also going to be a part of the phase threes.

No, it's not. So we did aqueous humor taps several times during the phase two. And aqueous humor taps are not something that doctors necessarily do commonly in the office. And if you look at the literature, and while there isn't great literature on this, there is a high rate of infection, much higher with aqueous taps than there is with intravitual injections. And unfortunately, in one patient in the Duraview arm and one patient in the ileal arm, immediately following an anterior chamber tap, there was a case of infection and ophthalmitis. Now, fortunately, both those patients did well. It was picked up rapidly and they were well treated. But after the second case, we stopped doing the aqueous humor taps, obviously for safety reasons.

Got it. That's helpful. And I guess maybe just on that point, you know, we know retina docs are very sensitive when it comes to safety, especially with more serious AEs like endophthalmitis. I guess, can you just remind us again overall of some of the details about DERVU's safety profile to date?

Yeah, as I said, and I'll repeat, the 190 plus treated patients, there were no ocular or systemic SAEs due to our drug, and there were no safety signals. There were cases of endoplamitis, we just discussed one in the Duraview arm of W02, and one actually in the control arm, in the ILEA arm from aqueous tabs. But those occurred immediately after the aqueous tap, not in conjunction with, obviously, in the control group, there was no DERVU in the eye, but it was many months after the DERVU went in. Endophthalmitis occurs at the time of injection when bacteria, typically from the patient's floor, is introduced into the eye. So it occurs days to maybe weeks after an injection. So if you have an injection that was performed many months ago, and then temporally an ilea injection occurs, and a week later you get endophthalmitis, it's related to the ilea injection. And so we've had no, so far, reported cases of endophthalmitis temporally related to the injection of our drug. Now I have to say, this is an injection-related phenomenon. on. You do enough injections, you will get endophthalmitis. And if you look at the clinical trials, the phase three trials, and you look at what was the rate of endophthalmitis with the drugs, it varies from 0.4% to up to almost 2% in the phase three trials. And in the real world, which it's probably underreported, it's about 1 in 2,000, 1 in 3,000 per injection. Higher in diabetics, twice as high. So again, you need to take all that into account. It's a per injection. So if you're reducing the number of injections because you have better sustained release, you should theoretically at least reduce the risk of infection.

Jay, maybe just on that point, there were two other instances of endophthalmitis in a Derview treatment arm. I'm just, so we already established the first one was more with an aqueous tap. What about the other two that occurred?

Immediately following ILEA supplement, I think I said that.

Got it.

Many months after the derby went in. One was three months, the other one was five months, I believe. And so immediately following a supplement of ILEA.

Got it. Thank you so much for that. Well, we're kind of at time here, but I do want to ask George if you can just remind us about the cash position and if you can remind us about the runway and what that runway is expected to cover.

Yeah, so what's, you know, we've been very judicious with our spend. Obviously, most of it is on our clinical trials and also our preparation for the NDA and our commercial scale up for manufacturing, which is equally important because, you know, once we report our data this summer, everyone's going to say, where's your NDA? Where's your CMC package? And that is well underway. And so our cash guidance is into Q4 of 2027. We ended last year with a little over $300 million of cash. and we expect to have well over a year of cash when we read out data this summer. So we're in a great place. Our cash guidance is unchanged and we're funding all four phase three trials that are ongoing, our beautiful Northbridge facility and all of that CMC preparation. So we're in a really great place.

Got it, got it. Great to know. Well, Jay, George, that's all the time we have. Really been a pleasure hosting you both this morning at our ophthalmology conference.

Thank you, Lisa.

Well, that ends the session, everyone.