EyePoint, Inc. (EYPT) September 2026 Conference Transcript

Good morning, everyone. I'm very happy to be kicking off day two of our healthcare conference with the iPoint team. I'm joined here by iPoint President and CEO Jay Duker, CFO George Elston, and CMO Ramiro-Ribiero. So thank you, all three of you, for joining us early on a Tuesday morning. Just a quick note on our research disclaimer. Please feel free to visit morgansanley.com slash research disclosures for our disclaimer. So let's get into it. It's been an eventful a few months for the iPoint team. Maybe we can start on the recent Lugano trial readout, the phase three readout, the first of two phase threes that you're going to have this year. You know, we look at the data headline. The study didn't technically meet the primary endpoint in the full intent to treat population, but there were a number of encouraging findings underneath that headline. So we'd love to hear you guys walk through your interpretation of the data and importantly, what may have the market missed Thank you very much for the invitation.

Thank you for the question. So the Lugano trial was a phase three trial which studied our virulinib intravitreal insert, 2.7 milligrams per dose. Virulinib is a small molecule tyrosine kinase inhibitor that has activity against all the VEGF receptors, PDGF, and JAK1. The control arm in this study was on-label 2-milligram of Flibercept. We're studying it in wet age-related macular degeneration. And the patient population, 75% of them were treatment-naive, and 25% had been previously treated. The primary endpoint of the study was non-inferiority change in visual acuity from day one to the average between week 52 and week 56. So as you mentioned in the full analysis set, we did not meet the primary endpoint, but there was some really encouraging data that came out of the study, including the important secondary endpoints. First of all, safety. In the prior phase two, phase one trials that we won with the insert, we really had no safety concerns, and that was really backed up in the phase three. The safety looked quite clean. We also showed really good anatomic control of wet AMD. That's measured in the office by an instrument called optical coherence tomography, or OCT, and at the end of the trial, there was only a negligible difference in retinal thickening between the study arm and the control arm. We were able to reduce the treatment burden by over 40%, which if approved and in the real world could mean two fewer injections per year on average. And over half of the wet AMD patients went the full year under control with our drug alone. And in that group of patients, we were statistically non-inferior in change in visual acuity. In the overall population, however, one of the things that really stood out as highly unusual is the number of eyes in the control arm that lost 15 or more letters. Historically, that occurs because some eyes just don't respond to anti-VEGFs, and remember this is an elderly population, so some of these patients will lose vision for other reasons, like cataract or glaucoma or dry AMD. Typically, in the 2-milligram ILEA arm, at the end of a one-year trial, you expect between 4% and 5% of the eyes to lose 15 or more letters. In the Lugano trial, it was only a half a percent, and that, again, is statistically highly unusual. And we believe that was the primary reason for the miss. It certainly wasn't that our drug wasn't active. Again, looking at the secondary endpoints, our drug was durable and potent and safe. But there appeared to be a significant mismatch in these 15-letter losers. And if you go back and look at our Phase II trial, the DAVIO-2 trial, 7.7% of the control arm, the same control arm, 2-milligram ilea, lost 15 or more letters. So it went from 7.7% to a half a percent. And in the phase two, in our high-dose arm, it was under 4% lost 15 or more letters. And when we really broke it down, we ended up with nine patients in the Duraview arm that lost 15 or more letters for something other than wet AMD. And in those eyes, when we looked at the visual difficulties and, of course, the anatomic control in the overall clinical findings, six of them lost vision due to geographic atrophy, the severe form of dry AMD, versus none in the control arm. Again, highly asymmetric and unusual. Two lost vision due to glaucoma and one from a successfully repaired retinal detachment where the patient developed a severe cataract after the successful surgery. So we believe that this asymmetry in the 15-letter losers was the primary reason that we missed the endpoint.

Okay, that's really clear. I mean, it sounds like, you know, the control arm simply just performed a lot better than you would have expected based on historical trials. In terms of the nine Duraview patients that actually experienced a 15-letter or greater vision loss, can you help us understand what you think happened in those nine patients? I know you mentioned geographic atrophy?

So the geographic atrophy patients, I think, again, at the end of the trial, if you looked at their anatomic control of the wet AMD, it was quite good. And in fact, of those nine patients, three of them never received a supplemental injection. And the reason they didn't receive it is the treating physician felt that there was no active wet AMD and there was no reason to give them another anti-VEGF. So we then did some further analysis to look at the possibility of our drug speeding the growth of geographic atrophy. Now, we certainly hadn't seen that in any of the prior studies, and there's no preclinical data to suggest that. And in fact, The analysis that we've done, I think, shows quite clear that not only do we not cause new geographic atrophy, but in pre-existing geographic atrophy, the rate of progression was no different than the fellow eye, for example, which is a nice internal control, and was actually less than what's been reported as the usual progression of geographic atrophy. What we did find is the eyes in the DuraVue arms started with geographic atrophy closer to the center of the fovea. And that means that even if they progress at the same rate, obviously if you start closer, you're more likely to have visual loss from that. So we think, again, it's just an asymmetric distribution. The two patients that had a loss from glaucoma, one of them, unfortunately, every time they got an ILEA shot, which was part of the trial for them to get ILEA at the beginning, they spiked their pressure very high due to the ILEA shot. And clearly, if that patient had been randomized into the other arm, they would have received ILEA and had the same pressure spikes. So, again, it appears certainly just a little bit of bad luck with the randomization in those cases.

Okay. That's helpful context. And then when you think about the 42% reduction in the treatment burden that you highlighted, How do physicians think about that magnitude of reduction in the context of real-world treatment burden in the disease?

So I think, again, overall, the physicians we spoke to, and we've spoken to a lot of retinal specialists and shown them the data, they're quite enthusiastic about the secondary endpoints, including that reduction in treatment burden. The expectation or hope going into the trial from retinal specialists was that we would have at least a 20% reduction in treatment burden. And when you look at the real-world analysis of medications like Hydrocylia and Fabismo, which have been very successful, these second-generation anti-VEGFs, they appear to reduce treatment burden less than 20%, about one injection less per year on average, yet they're quite successful. So we think that overall success of the reduction of treatment burden, if approved, would be very enthusiastically accepted by the retinal community.

Okay. And then just going back to the safety profile for a moment, it looked quite clean, as you mentioned, including after repeat dosing. So no meaningful imbalance in interocular inflammation, no observed retinal vasculitis or severe IOI. So how important is sort of the repeat dosing safety experience when you think about the differentiation of your drug?

Well, again, these patients on average who are diagnosed with wet AMD live for over another 10 years. And so you want to be able to treat them successfully and safely for the rest of their lives. So the important thing in wet AMD, when you look at the long-term success, patients, despite our very good short-acting anti-VHF, still lose vision. And so the ability to retreat and have long-term suppression of VEGF appears to be associated with much better outcomes in the long term. So obviously you have to show the safety and efficacy in your trials. So we're certainly able to show safety with repeat dosing. And again, we expected that animal data in the previous safety from single injection really gave us confidence that we would be safe. But if a drug can't be repeated, and obviously if it's even a long acting that might last six months or a year, it doesn't really help us retina specialists treat patients in the long term. You need to have repeat dosing.

And then just thinking about the takeaways from the study, is there anything you learned from Lugano about patient selection or baseline patient characteristics that could influence how physicians would use to review commercially?

So we've looked quite a bit at the outcomes to see if there was any indication that, for example, the drug worked better in eyes that were previously treated or eyes that were treatment-naive, and we didn't find a difference. We've broken it down by some other parameters, and we'll continue to do that, certainly, because that's something, if approved, is very important. You want to be able to tell the treating physicians which are the eyes that are going to do really well. And especially that 54% that went the full year with our drug alone, as I think I've emphasized over and over, we have these supplement criteria in the trial, but that's not how doctors treat in the real world. They don't supplement per se. But given that we're a different mechanism of action, I think in the real world, if we're approved, doctors wouldn't hesitate to use both a biologic ligand blocker and a long-acting TKI together to get, hopefully, a synergistic effect. So, again, when we look at those eyes that made it through a full year stable on our drug alone, we're hoping to find some biologic marker early on that might indicate that subgroup of patients. But as of yet, you know, when we looked in the phase two, we were not able to discern it, and we'll be doing further studies to try to elucidate that.

Okay, great. Just given the totality of the data and the outcome, what conversations have you had or are you expecting to have with the FDA around this study?

So I think, again, putting it in context, the FDA has seen a lot of Aflibrosep 2 milligram arms and how they do. And I think we have a very solid clinical explanation as to why we missed the primary endpoint. And there are certainly examples in retina of drugs that hit one phase three and missed a second phase three being approved. And there are plenty of examples outside of ophthalmology of that as well. And so if the second trial, the Lucia trial, is positive, we're quite optimistic that the FDA will accept our NDA and review it.

Okay. That's a good segue to Lucia, which I know is coming up next quarter. On Q4, you've guided the street. This is obviously an extremely important readout for the company. So can you remind us how similar the trial is to Logano and whether there are any meaningful differences in sort of the patient population that we should be thinking about?

Romero, do you want to answer that?

So in terms of study design, Lugano and Lucia are identical, exactly the same type of study design. In terms of the patient population, the only difference is that Lugano was 100% U.S. patients and Lucia is 80% U.S., 20% international. We published the mask baseline characteristics earlier this year in a medical conference, and the baseline characteristics on a mask fashion was pretty similar. The way that we are analyzing the data also, of course, pretty similar. We are amending the analysis plans for RUCIA based on the learnings from Lugano. So one new analysis that we're going to be doing is looking at patients that lost 15 letters for reasons not related to wet MD. And similar to what we did for Lugano on a post-hoc matter, removing those patients, in Lucia, we're going to pre-specify that and has a pre-specified sensitivity analysis. The primary endpoint, it's still the same, takes into account to all the patients, but for the sensitivity analysis, we will remove those patients.

Okay. Ramir, just going a little bit further on the geographic mix, how do you think that could influence either the control arm performance in Lucia or maybe just the underlying variability in visual acuity outcomes?

Yeah, I think if you look at recent Phase III studies in wet MD and when they broke down by geographic region, there was no meaningful difference between U.S. and international patients. In the end of the day, wet MD is a relatively genetic disease, so you see mainly in Caucasian patients. The sites that we use outside of the U.S., of course, are sites that have experience in Phase III studies. They are located in big cities, so we should not expect any difference in terms of geographic region between U.S. patients and international patients.

Okay. So the timeline you've outlined is Q4 for Lucia data and then potential NDA filing in the first half of 27, right? So what would you really need to see in Lucia to feel comfortable moving forward with the planned NDA?

I think it's actually quite binary. If we have a positive primary endpoint, we intend to move forward with the NDA filing in the first half of next year. And so from the perspective of acceptance in the retina community and use, I don't think the retinal physicians will care very much about the actual numerical difference, if there is one, between our drug and the control arm, as long as we're approved and safe. So we would expect to see similar secondary endpoints in Lucia that we saw. And if we do and we hit the primary endpoint, then I think we intend to file, and I think we'll have a good chance of having the drug accepted.

I guess in your conversations with retinal specialists, do you feel like there's still a lot of enthusiasm around the program and kind of belief that you guys have an active drug here?

Oh, I think there's a lot of enthusiasm, yes, in that, again, when they look at the secondary endpoints, in particular the anatomic control, which is what retinal physicians use on a daily basis to decide how well their drug of choice or their interval is working, I think they're very enthusiastic about it. What a drug like the Verlinim insert can do for them and their patients is, first of all, the most important thing is it will really help long-term visual acuity because in the long term right now, patients are undertreated. And by having an insert that lasts six months or longer, the ability to treat in the long term and have patients come back for visits I think is going to improve and retina specialists clearly understand that it also gives them flexibility to change their dosing frequency longer if they choose to depending on the patient in this situation and so I think the enthusiasm is there and I think that in general the secondary endpoints, we did better than expected in the retina community, and that's what's really going to make us commercially successful. We have a hurdle we need to get over, which is we need to hit the primary endpoint in the next trial and obviously get approved.

Of course, yeah. Maybe just on the commercial opportunity and sort of the competitive backdrop, you know, the competitive bar has certainly been raised by increasingly durable agents like ILEA, HD, and of a bismal that are on market, what would Duraview need to offer just in practice to drive actual switching from those agents?

Well, I think the obvious thing is, again, further length of time between injections. If you really look at the real-world data, whatever agent we use, about 20% of what AMD patients still have to be treated monthly. And about half have to be treated every two months or more frequently. And so there's a huge need out there, even with these newer agents, to try to extend those patients out further. And so again, I alluded to this earlier. If you have a patient that you're treating 12 times a year, and let's hypothesize that the review is safe, effective, tolerable, and approved every six months, and you use it in that patient, and you still need to or choose to use a ligand-blocking biologic in between and say, you know, your total four times a year injections, those two, you know, what we called in the trial supplements, those wouldn't be considered supplements in the real world, because in the real world, you've gone from 12 injections a year to four injections a year which is terrific for everybody and if you go back and look at the data from Lugano almost 90 percent of the eyes were controlled with four injections or less per year and again going back to the real world if you ask the question well how many high-dose ilea patients or Vibaismo patients are treated at a three-month interval or longer, it's not 88%. It's probably a third of that. So that ability to get many patients out to that three-month or longer mark, I think, is something that's going to be very attractive to everybody, patients, physicians, payers.

If I can add to that, I think because the topic switching comes up frequently, and that's been the history of how wet AMD is treated. The most recent drugs say, we last longer, use us, stop using the other programs. And our message is quite different. Our message is it's no longer either or it's both because we're bringing a new MOA. We're going to be that background foundational medicine. And if the anti-VEGF biologics are needed in between, doctors will use them. And so it's really a different commercial mind shift in that space.

To your point, George, that means that flexibility to actually give supplemental anti-VEGF injections on top of DuraVie when necessary. That kind of lowers the bar to entry when it comes to practice.

Yeah, I think it totally does. And I think even though we showed over half the patients could go six months on our drug alone, it doesn't mean that that's what the majority of doctors will do. Certainly at the beginning, they're going to want to see how the drug performs. And remember, many of these patients do not have wet MD in the fellow eye yet, and they're susceptible. So I think the idea of going six months or longer between visits is not something most physicians are going to be comfortable with. They're going to bring the patients back to see how they're doing and check the fellow eye. And I think that some patients would be very happy to come back for a check to hear they don't need an injection. Or, as I think I've already mentioned, some doctors, even if the eye's under control, may choose to use the assumption that the two MOAs are going to be synergistic. choose to do that. That's the flexibility that our drug may offer.

Okay, makes a lot of sense. I'm going to just switch gears for a moment to your diabetic macular edema program. Maybe you could, Jay, remind us why you believe DME could be an attractive setting for DuraVue.

Well, I think first of all that the diabetics, it's a different population from what MD patients, They're younger. They're often working because they're diabetics. They have multiple doctor visits, and it's really hard for them to have the number of injections that they need. The study suggests in the first year of DME treatment, patients should receive about 11 injections, and in the real world, they receive about three. and some of that is that because DME is a multifactorial disease, it's not just VEGF-mediated, there's clearly an inflammatory component as well, that it can take multiple injections before the patients realize that they're actually getting better. So if you're a diabetic and the physician says, look, I've got to give you these monthly injections, you have three, four, five of them, and you don't perceive the benefit, it's very easy to stop coming back and we think that's a real problem in this population. So the thing that really gives us really enthusiasm about our drug and DME was the results of the Phase II trial, the Verona trial. We looked at patients who were previously treated, but all of them had active DME, which means they had decreased vision and they had fluid on OCT. And if you look at the initial data point after treatment, All patients received treatment on day one. And at week four, the eyes in the Duravu arm were already seeing about four letters better than the eyes in the ileal arm. And there were also 40 to 50 microns drier on OCT. So if we can show that in the phase three, even if the end of the trial were non-inferior, were the same vision, but we can show we can get patients drier and seeing better faster. who wouldn't want to have better vision with fewer injections. I think everybody would. And I think that that ability to capture market share in the DME market, which is currently about a $3 billion market, I think it's wide open for a drug like ours.

So you mentioned the Phase III that are ongoing, Phase III COMO and CAPRI trials. They're now both fully enrolled, more than 480 patients in the trial. and I know you're expecting top-line data from those trials. I think it's Q4-2027, if I'm not mistaken. So can you walk us through the design of those trials and sort of what you learned from Verona that may have informed some of that planning?

Yeah, so similar to our wet MD, Coleman-Capri are two identical studies. The main difference first on the control arm, we're using on-label Aflibrocept, which means five monthly injections in the beginning and then after that is a fliborcept every eight weeks. On DuraVue, based on what we saw in our phase two study with the benefit of DuraVue starting from day one, we are dosing DuraVue day one together with a fliborcept and then after that we have two additional monthly fliborcept and then DuraVue is every six months. So day one, 24 and then 48. The primary endpoint is change from baseline to average week 52 and 56. So this is similar to our phase three program. And then the secondary endpoints, we also have treatment burden, anatomy control, and safety. We also have supplement injections for patients that meet a certain criteria. And then we have both naive patients as well as previously treated. Most of the sites that are part of Coleman-Copier were also part of our wet MD study. So those sites, they have experience with phase 3 studies and they have experience with 2Review, which, of course, from an operation perspective, help us a lot.

Ramiro, maybe you can just give some context. I know it's a year away, but what do you think would constitute a compelling clinical profile in DME beyond just non-inferiority, what we want to see in those phase 3 trials?

I think the key components are, of course, the non-inferiority, which we have agreement with the FDA to use a non-inferiority margin of 4.5 letters, followed by a reduction in treatment burden, which also is important for DME. Safety, we have a good understanding of safety. We should see the same type of safety profile in DME patients. And then in addition to that, as Jay mentioned, it's going to be very interesting to assess the effect of the JAK1-IO6 inhibition that we have with a Rololib in DME patient. This can translate to first either a gain in visual acuity earlier than just a fliborcept, and then second, which is very important for physicians, is a reduction in the leakage on the fluorescein angiography. We know that long-term patients that have leakage either on the OCT or on the FA if I have worse outcomes than patients have dry retina.

Okay, that's helpful context. George, I'm going to turn to you. Just thinking about the balance sheet, you ended the second quarter with about $180 million in cash, and you've got runway into Q4-27, so you're well-funded here. But how do you think about cash utilization following Lugano? And, you know, I know you've been investing ahead of the launch, but how do you think about cash spend going forward?

Yeah, no, great question. And, you know, I think we've got a pretty good track record at my point of managing and controlling our burn. Our cash guidance has been unchanged for over a year. Obviously, with Lugano missing, a number of things have pushed out. And so we're still very confident in that cash runway is probably a little bit better. But, you know, clearly between now and then we'll need to add to the balance sheet. We've got a number of catalysts, including Lucia, including the potential NDA filing and acceptance. And as you mentioned, Como Capri next year. And so I think with success in Lucia, we'll have a number of levers we can pull, including potential synthetic structures on top of equity and other mechanisms like that.

And just on the point of the sort of investment ahead of launch, I know you've been bringing in commercial leadership and kind of building out your manufacturing capacity. Can you talk about sort of the prep work that's going into that?

Yeah, so I think what gets lost out there, obviously, there's a lot of focus on the clinical outcomes, and that's clearly important. But when you file an NDA, CMC is just as important, if not more important, in the sense that most CRLs happen on the CMC level. And so we've been in front of manufacturing for several years. We had a state-of-the-art facility built for us by our landlord in Massachusetts. And so that has been under scale-up, and we now have batches under stability. We have for registration batches, and we're in the process of scale-up to support that CMC, and the team's just done a remarkable job out there. And then on the commercial side, it's never too early to get in front of your customers, start talking to payers, and we've built a very small but important team in preparation for launch. And I think the bigger spend on the commercial side will obviously come after NDA acceptance and approval where we'll start to build that organization out.

One more comment, if I may, about the manufacturing. So these inserts, there's a lot of technical know-how that goes into making them. And the other big effort we needed to do at our facility in Northbridge, Massachusetts, was automate the process. In order to really meet the demands of a successful launch, the inserts really need to be made not by hand but by machines. And, again, George said it, and I'll reemphasize, our team has done a remarkable job to automate and semi-automate the process from the beginning right straight through to the inspection of the inserts. Formally, the inserts were inspected individually by hand. a person picked them up with tweezers and weighed them and measured them and looked at them under magnification for impurities. That's obviously not something that you can scale successfully commercially, and we knew that. That's one of the reasons we built this facility and brought in the type of automation that's necessary. We've been able to do that successfully. Just to give you the last word, Jay, Lucia is around the corner. you know a lot to be excited for what do you think investors will understand with a positive lucia data that they may not appreciate today so i again i i'd like to emphasize the secondary endpoints because that's what's going to make this drug commercially successful what we're trying to do here is really improve patients lives by giving them better long-term vision And the pathway to do that is through those secondary endpoints. So that, I mean, it's obvious we need to hit a primary to get approval, but we are quite optimistic that with the primary endpoint being hit in Lucia in the strong secondaries and the clinical explanation for the MIS, I think the agency is going to look quite favorably at the application.

Terrific. Well, thank you. We're wishing you success in Lucia, both for the iPoint team and for patients. So we'll stay tuned, and thanks for joining us today. Appreciate your time.