Good morning, everyone, and thank you for joining us for the EyePoint Pharmaceuticals chat. We're pleased to have George Elston, CFO of EyePoint, here today, and Ramiro Ribeiro, Chief Medical Officer. You all have reached a pretty good milestone today, so congratulations on that. I guess before we get into that, maybe you want to give us a quick overview and lay of the land to level set everyone, and then we can launch into some Q&A.
Great. Yeah, thanks, Annabel, and thanks to Staples for inviting us to the Ophthalmology Conference. Yeah, we're very excited about our news, and I'm going to let Ramiro talk about that in depth as we go through the Q&A. We announced this morning that we've completed enrollment in the first of two phase III pivotal trials for DURAVYU in wet AMD. We enrolled over 400 patients in seven months. Great investigator and patient enthusiasm. The second trial, which is labeled Luchia, is now 60% enrolled, and we've guided that that will complete enrollment sometime in Q3. The nice thing about that news is we're looking now at data mid-next year for the Lugano trial. I think coming back to kind of our overview is, you know, EyePoint has been a story about execution, and this is just another example.
You know, we were talking last week that we actually dosed our first patient for DURAVYU in January of 2021, and here we are in mid-2025, completed the first of two trials. You know, it's been a really great time to be here at EyePoint. I think we're just to come back to the opening, you know, we're really focused on delivery of drug to the back of the eye. We're excited about DURAVYU, which is vorolanib, a very potent and selective TKI that blocks not just all isoforms of VEGF, but also PDGF. We have shown in an animal model that it's potentially neuroprotective. You know, we've been laser-focused on developing that program, moving it into now phase IIIs in wet AMD.
Earlier this year, we reported really positive 24-week data in DME, and we now have an end of phase II meeting with FDA in early July, and we'll update the street later this probably early fall on plans for that. DME is a 2026 event. We've previously discussed that this year and into next year is all about execution and getting the phase III trials enrolled. Beyond that, we continue to look not just at data next year, but, you know, getting our NDA filed and working through the CMC section. We have a brand new 41,000 sq ft facility in Northbridge, Massachusetts, that is scaling to potentially make millions of doses to support the global launch. That team has really been excellent in their execution.
We're in the middle of starting registration batches to prepare for the NDA filing, but also thinking about pre-approval inspection and, you know, ultimately commercial launch. Things are going really well here. We issued earnings several weeks ago. We have cash into 2027, which is well beyond our data readout next year, and we're excited about the future.
Fantastic. Maybe we can just talk a little bit big picture. Wet AMD and DME markets are obviously very well served by anti-VEGF, even some longer duration. How do you envision, and I know this has been tossed around many different times, how do you envision TKIs fitting into the treatment landscape? Do you see it as a complement, or do you see it as a potential replacement? You know, outside of duration, are you trying to provide some other type of solution? Maybe you can just go big picture from that point.
Yeah, maybe I'll answer that initially and ask Ramiro to comment. At EyePoint, we've always maintained that DURAVYU is not another anti-VEGF. In fact, you know, as we think about our program, and if you think about our program from the beginning, we've always positioned DURAVYU as a maintenance therapy in wet AMD. Get your patient stable, put in DURAVYU. If our phase II data holds, you know, we should be able to take two-thirds or more patients six months or longer with nothing else. That's just on the duration story itself. You know, we believe that DURAVYU brings a new mechanism of action to this disease. If you think about wet AMD historically, it's essentially been the same mechanism of action. It's a ligand-blocking biologic. We believe we bring something new. We're not saying use us now, not them. We're saying use both.
If our, again, based on our phase II data, there's great evidence to support that. Ramiro, do you want to add to that?
Yeah, good morning, everybody. Thanks for the question about, I think the way that retina physicians see wet AMD with the treatment of anti-VEGF is that those drugs, they work really well for those patients, but they do require a lot of frequent injections. We see that there is a big unmet need with longer duration therapies. I think we see this highlighted by the enrollment in our phase III study that shows that there is a big need from patients and physicians looking at therapies that have longer duration. The way that physicians and patients think about wet AMD today is mainly as a monotherapy. There is just one therapy class of drug, anti-VEGFs. As George mentioned, we're bringing a new mechanism of action. It is not going to be either anti-VEGF or TKI. It is going to be a combination of both, providing greater outcome for patients.
We saw in our robust phase II data that patients were able to go up to six months. That was 66% of patients without receiving any anti-VEGF. And 50% of the patients with one single DURAVYU went all the way to one year without any anti-VEGF. We also have some preclinical data that shows that TKI inhibition with vorolanib from our DURAVYU compound has a potential effect on fibrosis, neuroprotection. So those additional benefits we're going to be exploring in our phase III study.
Just mechanistically, can you talk a little bit about this antifibrotic and neuroprotective quality about the TKIs that you don't get with just straight VEGF?
Ramiro, you want to take that?
Yeah, I'll take that one. One of the benefits of vorolanib is that we are blocking the receptors intracellular. Number one, we block the VEGF receptors, but also we block other receptors. One of them is PDGF. By blocking the receptors on a constant therapeutic delivery, because we're using the drug delivery system, there is less fluctuation of the disease. We saw that in our phase III study where we showed that the CST had less fluctuation. One of the hypotheses is that if you have less fluctuation of the disease activity, you might end up with less fibrosis, which also has a neuroprotective effect.
Yeah, and just one point to that, Annabel, is I'm not sure all the TKIs have demonstrated that. I know in our case, we've published our neuroprotective data. I don't believe the competing molecule has done that yet.
Okay, I see. Is it that they haven't shown it, or is it that they don't have that capability?
I don't know. Do you know that answer, Ramiro? I don't think that they've done that work.
Yeah, I do not know.
Okay. Maybe you can talk a little bit about physician reception to the adoption of a new mechanism and incorporating this into anti-VEGF treatment. You're effectively changing their treatment paradigm, extending the duration of response, changes their practice a little bit. Maybe you can talk about not just the reception to a completely new mechanism, something that they may not be as comfortable with, and also how it might change their practice.
Yeah, so Ramiro is actually a retinal specialist, so I'm going to let him answer that question.
Yeah, no, great. I think the retina community as a whole is always looking for innovation. Annabel, if you look at the pipeline in retina, it is very robust. We have seen the new generation of anti-VEGF for the past few years being highly adopted by the physicians. The intent of those medications is essentially to increase the treatment interval, essentially decreasing the treatment burden. Those medications were highly adopted by the retina community. I think what we are bringing, a new mechanism of action with the intent of providing vision outcomes for patients while reducing the treatment burden, is something that is seen as something that needs to be addressed by the retina community and patients. I think this was highlighted in our phase III study and how rapid enrollment happened there.
Yeah, I think just maybe to add to that, the beauty of DURAVYU, it's actually administered through a syringe injector. It doesn't disrupt practice. It's shipped and stored at room temperature. As we think about the commercial execution, it fits very nicely into current practice standards. The trials themselves were actually designed with that in mind as well. I think our label, if successful, will be very straightforward and easy for physicians to read and use.
Okay. Maybe you can talk just really quickly, review the phase II findings and talk about the safety profile today. These are clearly implants. You've got different doses that might require a different number of implants. Just help us understand that a little bit.
Yeah, sure. Ramiro, you want to review phase II?
Yeah. First, DURAVYU is an insert. It does not require any.
Insert.
Search for innovation. It's an insert. What we're testing in our phase III study is a 2.7 milligrams dose. For the phase II program, the DAVIO study, this was the largest wet AMD study evaluating a TKI technology to date. In that study, patients had previously been treated with anti-VEGF. They came into the study. They received three loading doses of aflibercept. Then we had three treatment arms. One was DURAVYU high dose, DURAVYU low dose, and we used aflibercept as a control. Aflibercept was given on label every two months after the three loading doses. What the DAVIO phase II results show is that it matched the primary endpoint at week 28, 32, that was the average BCVA. Visual outcomes were similar between the DURAVYU arms and the aflibercept, showing a noninferiority.
What is very important is that there was a big reduction in treatment burden for about 80%. When we look over time, six months after dosing with DURAVYU, 66% of the patients did not require any anti-VEGF. Up to one year, that number was 50%. So 50% of patients up to one year did not require any anti-VEGF. Even more important than that, in terms of safety profile, we did not see any SAE, ocular or systemic, related to DURAVYU. The safety profile of DURAVYU has been excellent, not just in wet AMD, but also in our other clinical programs. We have those more than 190 patients across our phase I, phase II studies, and our excellent safety profile continued in those programs.
I think, again, I think the safety profile DURAVYU is one of the things that we hear from investigators and their excitement on the phase III study that has been a study that it was easy for them to offer to patients because they were confident on the safety profile.
Okay. There have been some questions about the insert technology and whether it accumulates. That's happened to others in the past. Can you just give us a little background on that?
Yeah, sure. DURAVYU utilizes what we call Duracert E, which stands for erodable. That's kind of the evolution of the underlying Duracert technology, which has been kind of EyePoint's core for a long time. Previous iterations of Duracert were actually non-erodable implants. It includes products like Eutique and Iluvien. They were non-erodable because they had a polyamide shell, which controlled drug release. That shell stayed forever. For Duracert E, we've essentially removed that polyamide shell. The inserts that we're now using in the phase III are 94% drug, 6% matrix, and they're fully bioerodable. We've done animal studies to support that. Our phase III will actually be redosing every six months. We're excited to move that program forward.
Yeah, maybe you can talk about the design of the phase III, how it's different from phase II. What are some of the adaptations you've made, populations, patient populations, etc.?
Ramiro?
Yeah, I'll take that one. I think going back to our phase II study, this is, you know, of course, very important that we have a very robust phase II study because that taught us a lot on how to appropriately design our phase III program. We are following something that has been used for the past four approvals in wet AMD, which is a noninferiority study. Our Lugano and Luchia studies are identical. They have the same study design. Patients receive three loading doses of aflibercept in the beginning, and then they get DURAVYU or the control arm. We have one treatment arm for DURAVYU, DURAVYU 2.7 milligrams, and as a control, the aflibercept. The primary endpoint is BCVA, which again is very standard for wet AMD study. We are assessing that at one year.
What is important in our phase III study, patients are randomized enrolled on day one. Therefore, we're going to see the primary endpoint one year after that.
Is there anything specific about the inclusion criteria or even in terms of either rescue or retreatment? I guess there's slight differences between the different trials as far as when you rescue a patient. Can you help us understand some of the differences there? We just want to make sure that people understand that generally the trials are similar, but there's various tweaks that maybe they are not comparable across trials. Maybe you can help us frame that a little bit.
Yeah. I want to make it very clear, right? Lugano and Luchia are identical studies. From an inclusion and exclusion criteria, they are identical. We should have a very similar patient population. For those two studies, we are enrolling both naive patients as well as previously treated. I think we got good learnings from our phase II study on how to design those criteria. In terms of supplemental criteria, the supplemental criteria for Lugano and Luchia are identical. There is no difference between the two studies. We have essentially two criteria. One is a combination of vision loss plus increase in CST. The second one is hemorrhage that is because of wet AMD. Those two criteria are very straightforward. They are very useful in wet AMD studies.
I think we had a good learning from our phase II study on how to select those criteria.
Yeah, and maybe if I can add to that, Annabel, because we did a phase II, you know, we learned a lot. Remember, the phase II was a very heavily pretreated group. That patient population came in with an average of 10 injections per year. We did really well in that group. We had two-thirds make it six months without a supplemental injection. Actually, when Ramiro's team went back and looked, about 20% of those supplements met no criteria. As we looked at other reasons for supplementation, it really had no effect on vision. Remember, the primary endpoint for these trials is noninferior BCVA to aflibercept. As we looked at the supplement criteria in the phase III, we wanted to narrow that to things that really mattered, like vision.
As Ramiro stated, the primary, the main supplement criteria is a loss of five letters with 75 microns of new fluid. They must supplement. There is no negotiation. We have actually taken investigator discretion away in the phase III because of a lot of the things we observed in the phase II. I think ultimately, because we have now included these previously treated, I am sorry, these newly diagnosed patients, we expect that we will do better in the phase III because we will have a less needy population.
Got it. I guess one question regarding the phase III that you just mentioned. You have both naive and previously treated patients. How might that impact the outcome if you're having two different types of patients? Is this how it's always been studied? Or, you know, I noticed you're not sticking only with treatment naive or treatment experienced. So how should we think about how those results might evolve? And do you separate those different groups when you review the results? Are you looking at different sub-analyses?
I'll let Ramiro answer that, and then I'll come in with additional color. Go ahead, Ramiro.
Yeah. I think what is important for both naive and previously treated is that the inclusion criteria and exclusion criteria are the same. They have to have a certain amount of fluid in the retina, and they have to have also some vision loss because of wet AMD. Although some patients might have been treated in the past, we still believe that in terms of how they behave over time in the study, it's going to be relatively similar. Of course, we're going to be doing subgroup analysis, splitting between naive and previously treated. Again, I think we're confident because the inclusion criteria are the same, that both populations are going to behave similarly.
Okay. Got it.
If I can add one thing to that.
Yeah, sure.
Remember, we're doing a noninferiority trial. If randomization works, remember, we only have to tie. We don't have to beat. Again, going back to the phase II, by including the naive patients, we think that we should even do better.
Just on that, I guess, strategy to include treatment naive patients, is that sort of a suggestion you're trying to get in as early as possible? Are they always going to need anti-VEGF as an initial treatment and then move into TKIs? Or do you see a moment where TKIs will supplant that in some patients?
The trial was designed for regulatory approval. I think that's the case. We've never believed that you needed a load, but that was what was required for the FDA. We've gone down that path. Actually, if you look at the DME data, we did very well without a load. The inclusion was really to have both a wider label, but we also wanted our control arm to behave like the treatment groups did that got that noninferiority margin. We wanted to de-risk that as much as possible.
Got it. Got it. You know, maybe we can talk a little bit big picture. I know there's a lot of confusion out there about FDA guidelines. Some say they like sham. Some say they don't like sham. Some say there's no need for sham. They don't like sham. Can you clarify that for us?
Yeah, happy to. In fact, you know, that question comes up a lot, but I think it's a moot point from EyePoint's perspective. Two things. Number one, we've had a type C and end of phase II. FDA has seen our protocol and our plan and signed off on our use of sham, as they have with other competitors currently and essentially every program since Lucentis. Actually, there's nowhere in the draft guidelines, which are draft, by the way. You don't have to use them. That's been said publicly by the agency. And the word sham is not mentioned there. So there's one corner that seems to be raising sham as an issue, but it must be their issue because we're well aligned with the FDA on this.
Okay. Got it. You mentioned earlier you did design retreatment into your trial, correct?
We did. Every six months. It is a two-year. The phase III is a two-year trial. We will submit with one year safety and efficacy. We are redosing every six months over two years. We will do a supplemental NDA with the two-year safety, which will include a total of four doses for DURAVYU. Why? Because we want that on our label. That is what the agency told us. If you want redosing, you have to have that two-year data with 300 patients, which is why the studies were designed the way they were.
Got it. Got it. Okay. Maybe just one more question with regard to guidelines. Everyone is essentially seeing aflibercept as a comparator. Is it moving over to Vabysmo at some point, or is that FDA is okay with?
Yeah. The FDA has been pretty clear about that. The reason is you have to use Lucentis or Eylea because that's where the noninferiority margin was calculated. I expect perhaps over time, Vabysmo will become, but where it stands now, the agency is very clear. There's just not enough data with the newer drugs. From EyePoint's perspective, though, upon success with the phase III, assuming whether it's high-dose Eylea or Vabysmo in the lead, one of the first trials we'll do is a marketing study to head-to-head against the leader and time to first supplement. Where we have a real advantage there is we're six months or longer.
Okay. Got it. One question about just Vabysmo's label. They have a pretty wide label. It could be one month. It could be up to four months. The flexibility has worked out very well for them in the marketplace. Is there any kind of flexibility that you're designing into yours? What's your ideal label look like?
No, no, that's a really great question. We've really designed this from the beginning. When we talk to doctors about sustained delivery, remember, Duracert, we're delivering drug for about nine months, zero order kinetics. We're going for a six-month label because when we did our early work, that's what physicians want. Similar to, I know there's an ongoing struggle between Vabysmo and high-dose Eylea because of the label. Where we see a real benefit in our timing is we know we're giving drug for about nine months. Six months is the sweet spot. Say a patient presents at month seven, but you have a nine-month label, you can't redose. We wanted to give doctors flexibility, which is what's been built into our design.
Okay. Got it. I know we're running out of time, but maybe you can just talk about the timing of your catalysts and commercial readiness in the last minute that we're here.
Sure. Yeah, no, thank you. We continue to execute here at EyePoint. We announced Lugano today. We're very excited about that. Luccia is our next milestone, which we've now updated to be in Q3 of this year. From a data perspective, we'll have the Lugano 56-week data mid-next year with Luccia following shortly thereafter. Both trials will read out in 2026. From a commercial readiness perspective, we've been very active in that area. I talked about our manufacturing capabilities. We've been very focused on that to make sure that we can not just provide clinical material, but also get through an FDA inspection and registration batches. We have a pre-commercial team that's already doing early work with payers and KOLs.
We will be in a good position to not just execute there, but also get our NDA filed, which is something that Ramiro's team and our regulatory folks are already working on.
Great. Okay. I think that's all we have time for, unfortunately. Thank you for the quick overview, getting into the weeds a little bit with us. We're excited to see the enrollment of the next one and the next developments.
Great. Thanks very much, again, for having us.
Appreciate it. All right. Take care.