EyePoint Pharmaceuticals, Inc. Aktie

Great. First, welcome to Jay Duker and George Elston from EyePoint Pharmaceuticals here at the 47th Annual Goldman Sachs Healthcare Conference. Welcome, gentlemen.

Thank you very much.

For those in the audience and listening who may be newer to the story, can you start at a high-level overview of EyePoint say, core clinical programs that are advancing and key milestones that you have investors.

Sure. Happy to answer that question. And again, we really appreciate the invitation. So EyePoint is a drug delivery company for the back of the eye. We hope to improve patients' lives who have serious retinal diseases. Our lead product is called DURAVYU or EYP-1901. It's a combination of a small molecule tyrosine kinase inhibitor called vorolanib and our proprietary bioerodible delivery system. Vorolanib is a bit unique because it has activity against all the VEGF receptors. Again, it is a receptor-based treatment as well as PDGF.

And we also block the JAK1 receptor, which means we have an anti-inflammatory effect, which does appear to be important in retinal diseases. We are currently in Phase III in the 2 largest retinal indications, wet age-related macular degeneration and diabetic macular edema. The wet AMD trials are called LUGANO and LUCIA. They are traditional non-inferiority trial endpoints. And the first trial LUGANO is on target to read out sometime in August of this year.

The LUCIA trial is about 2 months behind and therefore, will read out approximately 2 months after that. The diabetic macular edema trials are still currently enrolling. And as of last week, they were 2/3 enrolled. They are simultaneous identical non-inferiority trials called COMO and CAPRI, and they should be fully enrolled in the third quarter of this year. Given that their endpoint is 56 weeks, the top line data should be out in the fourth quarter of 2027. So we have some really exciting milestones coming up in the next 1.5 years.

Great. Maybe dig in a little bit deeper in terms of kind of your view of the differentiation. So at a high level, where do you see the key differentiation versus standard of care from both standard of care as well as other emerging clinical agents?

Sure. So at a high level, what we can provide is sustained release anti-VEGF effect for 6 months or longer with a single injection. We have some excellent biologics that are direct ligand blockers that are approved. We have multiple biologics. And while some of them have extended duration, they really don't have sustained release.

My opinion, the only true sustained release that's approved is the port delivery system, but the differentiator there is port delivery requires surgery for placement. And our medications are injected in the office with a standard intravitreal injection procedure. And I might add, we do come in a prefilled sterile syringe injector shipped and stored at room temperature, which is not a major differentiator, but we believe commercially, the fact that we don't need to be refrigerated or frozen will prove to be an advantage should we be approved.

So I think the durability, obviously, is the big high-level differentiator. Now the next issue around durability, of course, people talk about reduction in treatment burden, how many fewer injections or visits will that provide? And while that's important, what we believe, and I think the retina community is coming to believe that durability with sustained release means in the long term, patients will get better vision. And that's really what we're trying to accomplish.

The reduction in treatment burden, let's call it a beneficial side effect of that, but that's not our true value. We believe the true potential value here is better vision in the long term. So that's the high level. I think also I mentioned that we do appear to have activity against the JAK1 receptor, which means we should reduce the downstream effects of IL-6 which is an inflammatory pathway that's been implicated in both DME and in wet AMD. That, again, can prove to be a differentiator for us. If we're approved with an every 6-month label, and we provide both anti-VEGF activity and anti-inflammation activity, I think that has the potential to set us apart from the current therapies and frankly, from the other therapies that are currently in study.

Yes. Let's dig a little bit deeper there. When you talk about especially some of your recent ARVO work around IL-6, JAK1, et cetera. Can you talk a little bit more detail on why you see the anti-inflammatory potential benefit as differentiated? -- specifically, how is that going to translate to meaningful clinical benefit and eventually commercial?

Sure. Great question. And let me kind of start at the beginning and what prompted this discovery that we were not only anti-VEGF, but we were anti-inflammatory. I'd like to go back and review a little bit of our Phase II DME trial, which is called the VERONA trial. And in the VERONA trial, we recruited active DME. It meant that they had fluid and they had decreased vision -- either to receive a single Eylea injection or an Eylea injection 30 minutes later with EYP-1901.

If you look at the week 4 result, the earliest time point, the eyes that received our drug were already 4 to 5 letters better than the eyes that received a single dose of Eylea, and they're about 40 to 50 microns drier on OCT. Now we believe we have a very good anti-VEGF drug. When we looked at that data, I said to the R&D team, I don't think we're that much better than Eylea. There must be something else active here.

And that's when we went back and did a further kind of analysis and discovered that the IC50 for vorolanib in the JAK1 receptor is about 80 nM, which means that the doses we're using in humans, we should be active against the receptor. Subsequently, we did some cell-based studies, including a study where IL-6 was applied in to cells and vorolanib was able at doses that were equivalent to what we're using in humans, reduce the downstream activity of the IL-6 by about 50%.

At ARVO, just recently, we reported another trial cell-based, which essentially looked at leakage from cells. If you add VEGF and IL-6 to cells, they will leak. If you then add an anti-VEGF, they leak less. If you add an anti-IL-6, they'll leak less. If you add both, you get minimal leakage. We then added vorolanib at approximately the dose we can get into humans, and we were essentially the same in leakage reduction as the IL-6 blocker and the anti-VEGF.

So as additional data to suggest that the anti-VEGF but we have do want to mention a couple of other things from the VERONA trial. I mentioned the rapidity of onset and also the rapidity of the dryness. But if you look at the eyes in Verona, and it was over 70% in the high dose that did not get rescued. They just received our dose our drug for 6 months. Those eyes improved over 10 letters.

Now again, cross-trial comparison is difficult. But if you look at the improvement in a previously treated population in patients receiving Eylea, it was less than that. In the Phase III, we've designed the trial to show this difference at week 4. We're dosing our drug at day 1. And at week 4, we can replicate the findings that we had in the Phase II. I think that even in the end, if we're noninferior to Eylea, but we can get the patients to see better faster and get them dryer faster, that means, I think, potentially a huge commercial success.

Back to VERONA, one other data point here, leakage in eyes can be measured quantitatively by fluorescein angiography and a reading center that's independent can rate the leakage, and that's a sign of inflammation. And in a dose-dependent fashion, EYP-1901 reduced the leakage more than Eylea did, another data point that suggests that this anti-inflammatory effect is real.

Great. We're going to -- we'll get into wet AMD and DME in a little bit more detail shortly. But before doing so, can you talk about the delivery platform and kind of how that is part of the story in addition to active.

Sure. Again, a great question. Just to remind people, EyePoint has been in the sustained drug delivery to the back of the eye space for almost 30 years. We've had 4 FDA-approved products with sustained delivery. All of them, however, prior were not bioerodible. The way they were designed is you had the drug had mixed with the matrix -- and then the drug disc or cylinder was then surrounded by an impermeable plastic that was inert. And the plastic was open. There was essentially pores at either end, and that allowed the drug to diffuse out.

And the reason you needed that is if you had a very soluble drug like a corticosteroid or ganciclovir, for example, without that reduction in the surface area, the inserts wouldn't last very long. So that matrix, though, is very similar to the matrix that we're using in the current version of EYP-1901, and it's been in tens of thousands of patients safely. The difference here is we removed that impermeable plastic. We want the whole surface area of the inserts to be able to release the drug because we wanted to get higher levels, number one.

And number two, we didn't want any residual long-term plastic to be remaining in the eye, given that on average, wet AMD patients can live over a decade requiring treatment. And so we really didn't think there was any reason to keep that design. So in effect, the current inserts are -- have less excipients than the 4 that were FDA approved.

In addition, what our scientists were able to do with the latest version is increase the payload of the drug. Our inserts are now 94% vorolanib. -- only about 6% matrix. That gives each insert payload of about 1.34 milligrams of drug, which means we're able to achieve high tissue levels with 2 inserts in a single injection. And our injector actually can hold up to 3 inserts, which, again, down the road, one could then potentially see the possibility of using multiple drugs in a single injection, which is something that we look forward to studying in the future.

Great. Very helpful. Moving on to, I guess, digging in a little bit deeper on wet AMD. Talk a little bit about VERONA and some of the prior data there. Can you talk about DAVIO 2 and how that underpins and plans within wet AMD?

Sure. So DAVIO 2 is our Phase II study in wet AMD. It enrolled approximately 160 patients, and they were randomized to either receive 3 milligrams of our drug versus 2 milligrams versus on-label Eylea control 2-milligram Eylea. The patients all were previously treated. And in order to enter the study, we only wanted to enroll patients that had responsive to an anti-VEGF. So they had to receive an anti-VEGF 2 weeks to 5 weeks prior to screening, and they had to show a response and then they were enrolled.

The primary endpoint was at month 8 in eyes were not reinjected with our drug. So they only received a single injection. And at month 8, we were statistically noninferior to Eylea and the actual numerical difference in the vision was only 0.3 in the 2-milligram arm and 0.4 in the 3-milligram arm. So that's 0.3 letters. And those of you who've been to the eye doctor, you read a line, that's 5 letters on a line. So it's less than half a letter difference, which is, again, statistically equivalent.

Equally important is we found that the safety was quite good. And we really had no safety signals that were identified in that trial. There were no ocular or systemic SAEs that are attributed to our drug or inserts. So we're quite pleased with the safety, and we've reported safety on over 190 patients from the Phase II and Phase I trials. And again, the safety has been quite good. From the perspective of, for example, the anatomic results, we measure anatomy using the device called the OCT, normal anatomy on OCT is up to 325 microns of thickness.

And anatomic control is important because in wet AMD, what's been shown is if you allow patients to gain fluid and have more leakage, even if you get it back under control, if that cycle continues, you can lose vision and get fibrosis as a result. So our maintenance of the anatomy was quite good in DAVIO 2. In the higher dose, the 3-milligram dose, there was about a 5-micron difference in the end between us and Eylea, which is really, really small. More importantly, to the doctors, having the fluid go up and down in a sawtooth pattern is something that they really don't like to see. And our fluid control is quite good through the whole study. And that's again important.

If you look at the eyes in DAVIO 2 that were unrescued, meaning they only got our drug, there was straight anatomic control all the way through. What that tells you is that the drug was working till the end because you would expect if the drug started to run out at month 7 or 8 or 9, you would start to see an increase in fluid, and we didn't see that.

So it gives us confidence that we truly have a 6-month or longer drug. Reduction in treatment burden was about 80% and about 2/3 of the eyes were free of a rescue up to month 6. And even though we didn't reinject the drug at 1 year, about 50% of the eyes in the DURAVYU arms were unrescued. So we had quite a good durability even with a single injection. So that gives us quite a lot of confidence going into the Phase III about the results. And we've obviously used what we learned in the Phase II to model the Phase III.

Great. So good transition to Phase III. Can you remind investors of study design and in particular, why you chose non-inferiority versus there's certainly other approaches out there? And then additionally, kind of the current status, you mentioned it earlier, but...

Sure. Sure. So noninferiority, the way the last 5 approvals have been in wet AMD have been using a noninferior approach. So it's a derisked approach. There's a lot of risk in this business. And our belief is that any time you can reduce the risk without harm to patients or harm to your label, you should. And so obviously, we're taking a derisked approach. Non-inferiority, again, the doctors understand it. They've seen it before. And our control arm 2-milligram Eylea is that's still the treatment of choice of a lot of doctors out there. And so when the data comes in, if we're noninferior to that 2-milligram on label, I think the doctors are going to understand very well where we fit into their paradigm. So noninferiority, again, to us is a derisking and it's the way to get to FDA approval, we believe, the fastest. So the study design is very similar to DAVIO 2, except in a few ways.

First of all, we enrolled the majority of patients who were actually treatment naive, about 75% treatment naive, about 25% previously treated. And we believe the addition of the treatment-naive patients, if approved, will not only help us on the label, but also derisk the trial. And what I mean by that is in DAVIO 2, we had a very tough-to-treat population. On average, in the United States, patients get about 6 injections a year. In DAVIO 2, if you looked at the prior year and normalized the number of injections, it was about 10.

And that makes sense because those are the patients we call frequent flyers who need a lot of treatment. We got very few easy-to-treat patients in DAVIO 2. And our hypothesis is if you have a patient who can go 3 or 4 months on any of the anti-VEGFs between injections, they should do really well with our drug. And we think the addition of the naive patients allows us to get a proportion of those easy-to-treat patients. So we think that's going to actually improve the end result.

The second difference, I mentioned already is we're reinjecting every 6 months over 2 years because we like an every 6-month label. We didn't reinject in DAVIO 2 at all. The third difference is we altered the supplement criteria -- we studied the supplement criteria in DAVIO 2 and found out that 3 of the criteria that we used did not result in an improvement in vision after supplementation. And therefore, you could call it a waste and supplement. And so we didn't include those in the pivotal trial. So ultimately, we think with positive data, doctors will know exactly how to use this and our label should be very straightforward.

When you think about what does good look like, how should investors frame BCVA in the context of non-inferiority?

Sure. That's a really good question and one that's very pertinent given that our data is coming soon. So I think the way to look at our data from the top line from the Phase III is really quite simple. The first is we need to hit noninferiority. We need to be statistically noninferiority. That's obvious. That's the primary endpoint.

But I'd also argue that the exact numerical difference probably doesn't matter. This is, again, a piece of data to share. But if you look at the wet AMD study of high-dose Eylea that got it approved, the high-dose Eylea arm was 1.4 letters worse than the 2-milligram arm. It doesn't stop us retina specialists from using it at all. It's a great drug because that amount of vision, we believe, is inconsequential to the patient. And frankly, the agency believes that, too. That's why the non-inferior margin letter or 2 or even 3 is in -- most of the physicians don't really care.

So I would argue that the exact numerical difference probably doesn't matter. We need to hit the primary endpoint. I'm going to reverse myself though and say, there's a chance we could be superior. And we're able to test for that without penalty if we hit the non-inferiority margin. Obviously, not guiding to this, but we could be statistically superior, even numerically superior. And I think, obviously, either of those, if we hit it, would be very beneficial to us commercially.

Now the second piece of data you should look for at the top line is safety. And those of you who follow retina companies, you know safety is of paramount importance. The good news for us is I've already mentioned the safety in the prior studies. And we've talked about this publicly. A few weeks ago, we had the DSMC meet, and they see not only the masked safety from the trials, they see the unmasked safety, and they didn't recommend any changes in the protocol of the trials, which is of a relief. We see a masked safety. And as we've reported publicly, the masked safety looks very similar to what we have seen in the prior 190-plus patients that we've already reported on.

So while the studies are not over, anything can happen, but I also like to remind everybody that most of the safety events occur at or just after the time of injection. And this last look at the safety, all the patients in LUGANO and LUCIA had received their second dose of our drug and about 1/3 of them had received the third dose. The third thing to look for at the top line is reduction in treatment burden. And we believe this may be the easiest bar for us to hit. And the reason is that it's a statistical superiority test for the FDA. And we only need to be 8% less than the control arm to be statistically superior.

Now the way treatment burden is going to be measured in this trial was a little different than prior. And I do want to go into a little detail about it so investors and analysts can understand because both arms of the trial get the 3-injection Eylea load at the beginning, those injections don't count for treatment burden.

In the DURAVYU arms, all eyes will receive 2 DURAVYUs mandated. In the Eylea arms, all patients will receive 5 Eyleas. So if there were no supplements and everybody follows protocol, the most reduction in treatment burden you could possibly see would be 60% -- we know there's going to be some supplements probably in both arms. But if you then look at DAVIO 2 and you say, what if you had the same supplement rate in DAVIO 2 as you do in the Phase IIIs, it'd be about a 35% reduction in treatment burden, which we believe would be excellent.

If you talk to the KOLs, and we talked to a lot of them and you ask them, what's your floor for using a TKI, they'd like to see at least a 20% reduction, which, again, remember, in a real-world situation, using a supplement is not a failure for physicians, that the idea of using 2 MOAs may be beneficial to patients. And therefore, just the idea of using a ligand blocker with a TKI may be an acceptable way to go.

So that's really the 3 things that I think are most important. I think we will likely talk about the anatomy and also talk about the percentage of patients that are rescue-free through the entire first year. While I'd argue also, given that the agency's interest is -- seems to be more in reduction in treatment burden, that figure is probably not as important. But I would hope that we could do at least as well as we did in DAVIO 2, where we were 50% rescue-free through the first year.

Switching gears a little bit to the commercial side. Obviously, a little premature, still need to get to the data. But to the extent data plays out as you expect, where do you see it fitting into the current treatment paradigm, especially vis-a-vis VEGFs?

So I'm going to, first of all, say it's never too early to think about that. I think that companies need to start to think about it even when they're designing their Phase I trial because this is a large continuum. We're focused on the clinical outcome because that's coming up, and it's easy to get focused on it. But we haven't just been laser-focused on that. We're focused on CMC because we know that, that's where most of the CROs come from.

And we're focused on commercial success because ultimately, what we're trying to do is improve patients' lives, which means we need to be able to get the drug to them. So it's not just how it fits into the paradigm is we need to be able to make enough inserts to satisfy what we hope to be a demand. But how it fits in, I think our data will help dictate that. But if you just look at us as a reduction in treatment burden, I think that we will be used in the majority of eyes.

If we provide an additional benefit, a visual acuity benefit or let's say, we can show we're antifibrotic at the end of the trial. I think doctors will accept then that in the long term, if we can reduce fibrosis, we will reduce vision loss. And they may choose to use us in the vast majority of their patients. And this is backed up by what we've heard on the podium by KOLs recently, where they have said, if approved, effective, tolerable, we use a TKI in 80% of our patients.

So I think at the beginning, it will be most likely used in the patients who require very frequent treatment. But I think once doctors get comfortable with it, if our clinical profile is what we hope, I think it's going to be used in the majority of patients.

Switching gears to DME. Let's focus on COMO and [ CAPRI ]. Can you talk a little bit more detail or give a little bit more detail on study design, specifically learnings from VERONA, -- you already mentioned a few, but anything more specific there as well as what investors should be looking for on the balance of the year as you march towards full enrollment?

Sure. So I would say that the study design in the DME trials is very similar to the wet AMD trials, 75% naive, 25% previously treated. The end of the trials are less, only 240 patients in each trial. And the reason we were able to use a lower end is that we will have the results of the wet AMD trials when we submit DME. And the agency has allowed us to use the safety data provided it's good, obviously, to inform the safety of the DME trial.

So we don't need to hit the safety numbers in DME that we would have otherwise. So the 2 big differences in the DME trials versus the wet AMD trial is we are dosing our drug of day 1. And there is a secondary endpoint of vision anatomy at week 4. So we hope to replicate in the Phase III what we showed in the Phase II because if we do and we can show as early as week 4 that we're better than a single dose of Eylea, even in the end, if we're noninferior and we're the same as Eylea or even a half a letter, let's say, or letter worse, but we're noninferior.

But we achieve the vision faster and we achieve dryness faster, I think the majority of retina specialists will choose to use us in almost all their DME patients because what patient wouldn't want to see better faster, I think they would. So that's the first difference. The second difference is a little bit more subtle, which is the label for Eylea 2 milligrams in DME is a 5-injection load, which is what we're doing.

The agency really insists in a non-inferiority trial that you use on-label Lucentis or on-label 2-milligram Eylea as your control. That's mandated. So we're sticking to that. But we don't believe the 5-injection load is necessary with DURAVYU, and therefore, we're only doing a 3-injection load. So very similar studies to wet AMD, but those small differences that I mentioned.

In terms of mechanistic rationale in DME, anything additional that you think the profile fits DME specifically?

I think I mentioned this already that we do have preclinical data with some supporting clinical data from VERONA that we have an anti-inflammatory effect. And so we expect to see that in the Phase III trials. And if we can show it, the combination of an anti-VEGF that's anti-inflammatory that's given every 6 months, delivered in the office, shipped and stored at ambient temperature, I think that has the potential to have a stand heads of everybody else.

From a -- I guess, mentioned earlier, commercial and I guess, never too early to start thinking there. Can you talk a little bit about the commercial and medical affairs readiness as well as manufacturing readiness that you're doing in advance of hopefully, good data?

I'm going to let George answer that.

Sure. So let's start with manufacturing. We have our own state-of-the-art facility. So we do drug development at EyePoint. So this facility was started 4 years ago. We have registration batches already on stability, and we are scaling up and preparing not just for building commercial supply, but also being prepared for pre-approval inspection.

The team has really done a remarkable job there. And we are just as prepared for that section of the NDA as we are for clinical data. So that is well underway, and we will continue to push that, especially through 2027. Interestingly, on our medical affairs team, we have a robust MSL group that we actually retained. We had commercial products several years ago, which we transacted. But we kept the MSL team, and they were really instrumental in helping us get our trials enrolled quickly, building relationships with the KOL community, and we've continued to add to that.

So that group is already on the ground as part of a more robust medical affairs team, which we think is very important, not just for wet AMD and DME, but also for commercial readiness. And then on the commercial side, we have a new Chief Commercial Officer, Michael Campbell, who joined us probably 2 months ago now -- in place about patient access, and that's really going to be key and part of our launch. And so while we have a small footprint right now on a commercial team, they're doing a lot of the leg work to be prepared on the other side of our data release starting this summer.

And obviously, with positive data, we'll be looking to scale that team up. We are planning to launch this product in the United States ourselves, and we will be ready for that. From a payer perspective, we've had initial discussions and have gotten very good feedback from payers as we think about where does DURAVYU position versus the current standard of care. And I think importantly, we're not another anti-VEGF. We're actually bringing a new MOA. And so we're really looking to position this program commercially in that same effect.

And I think the other interesting thing, and Jay touched on this a little bit, our product shipped and stored at room temperatures and some of our interactions with the larger practice groups and the private equity groups, the messages don't slow us down. And I think what's really unique about this program is we're this shipped and stored at room temperature. We're not taking up refrigerator space. And because it's a prefilled syringe, there's really no change in practice. So there's a lot of work between now and a potential commercial launch, but we've got the right team and right infrastructure in place, and there'll be more to follow.

Great. Briefly on balance sheet, can you remind investors current cash runway? What does it fund? And what does that include?

Sure. So our cash guidance has been unchanged for quite some time, and it's into Q4 of 2027. That includes all 4 ongoing Phase III trials and their readouts along with commercial scale-up for our facility and NDA filing. Obviously, the commercial -- I touched on this earlier, the commercial launch and scale up would obviously come on the other side of data.

But as we look out over the horizon, we've got the 2 Phase IIIs reading out this year in wet AMD. We'll have the DME trials reading out next year, NDA filing. So we have a catalyst-rich upcoming 12 months that we're going to be in a position to transact and fund the company. And we suspect it's going to be some combination of equity structure, and there's been a lot of interest from all of those groups on the other side of our data.

In our final little bit of time, maybe just in closing, what do you think is the most underappreciated part of EyePoint that investors don't -- they don't appreciate as much as you think they should.

I don't think there's a single thing other than the whole story. We are a derisked asset with, we believe, very good Phase II data going into the 2 largest anti-VEGF markets, total of almost $13 billion in the United States alone with data readout coming very soon. We remain quite confident and quite optimistic in the results, and we think we can make a difference for patients. And so I think as people dig in and turn their attention to us, they're going to realize how underappreciated we are right now.

Fair enough. Good place to leave it. Well, thank you so much for your time, and best of luck.

Thanks so much for inviting us.

Good morning. My name is Brittany, and I'll be your conference operator today. At this time, I would like to welcome everyone to the EyePoint First Quarter 2026 Financial Results and Recent Corporate Development Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request.

I would now like to turn the call over to George Elston, Executive Vice President and Chief Financial Officer of EyePoint.

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's first quarter 2026 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer of EyePoint. Jay will begin with a review of recent corporate updates and discuss our ongoing clinical programs for DURAVYU in wet AMD and DME. I will close with commentary on the first quarter 2026 financial results. We will then open the call for your questions, where we will be joined by Dr. Ramiro Ribeiro, our Chief Medical Officer; and Mike Campbell, our Chief Commercial Officer.

Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of the release can be found in the Investor Relations tab on the company website, www.yepoint.bio.

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, financial projections and our plans and prospects.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we have made or may make with the SEC in the future.

Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today.

I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of EyePoint.

Thank you, George. Good morning, everyone, and thank you for joining us. The start of 2026 for EyePoint was marked by a strong quarter of consistent execution as we approach a pivotal inflection point for our lead program, DURAVYU. We have strong conviction that the upcoming LUGANO and LUCIA readouts will catalyze our future transition into a fully integrated biopharmaceutical company, furthering our mission of improving the lives of patients with serious retinal disease.

We remain on track to deliver these Phase III top line data in wet age-related macular degeneration or wet AMD, beginning mid-year, positioning us to potentially be the first to market among all current investigational sustained release programs. In Diabetic Macular Edema, or DME, we are seeing strong momentum in our Phase III program with enrollment rapidly progressing to support our ambitious goal of full enrollment in both pivotal trials in the third quarter of 2026.

As we advance towards these significant milestones, we are confident that our clinically-rigorous, derisked and patient-centric approach will continue to reinforce DURAVYU's best-in-class potential in the 2 largest retinal disease markets. The fundamental strength of the DURAVYU program lies in its robust and differentiated clinical data. In Phase II trials, a single dose of DURAVYU demonstrated durable efficacy with improved vision and tight anatomic control.

In over 190 patients across 4 completed clinical trials, DURAVYU has demonstrated a consistently favorable safety profile with no safety signals. That profile continues to hold in our ongoing Phase III LUGANO and LUCIA trials for wet AMD as observed on a mass basis, where our low discontinuation rate of about 5% remains well below the 10% yearly average typical for wet AMD trials.

Importantly, none of these discontinuations were related to treatment. At this stage, all patients across the LUGANO and LUCIA trials have reached the week-32 visit, during which patients in the DURAVYU arms received their second DURAVU dose. Over 35% of those patients have since received their third planned dose of DURAVU at week 56. As a reminder, we received 2 consecutive positive recommendations from the independent Data Safety Monitoring Committee with a third review scheduled for later this month. We are optimistic that the interim masked safety data will continue to remain consistent, further strengthening DURAVYU's clinical profile.

In addition, we believe the multi-mechanism of action or MOA of DURAVYU's active ingredient, vorolanib, will prove to be a key clinical differentiator. Along with blocking all VEGF isoforms and PDGF at the receptor level, preclinical data supports vorolanib's ability to inhibit IL-6 signaling via the JAK1 receptor. With this unique ability to not only address both the vascular leakage and inflammation that contributes to retinal disease pathogenesis, but also potentially provide sustained release efficacy, DURAVYU is uniquely designed to deliver wide-reaching therapeutic potential.

Earlier this week, we presented peer-reviewed data at the Association for Research in Vision and Ophthalmology, or ARVO meeting that reinforces these findings and further substantiate DURAVYU's potential to improve long-term outcomes for patients. A primary kinase screen and subsequent measure of IC50 levels identified vorolanib as a potent inhibitor of JAK1, which plays a critical role in IL-6 mediated inflammation. In addition, vorolanib proved to be a potent inhibitor of IL-6 leakage in an in vitro cellular model. This data further highlights the multi-MOA potential of DURAVYU with the opportunity to bring a synergistic anti-inflammatory effect in addition to established VEGF and PDGF inhibition to the treatment of wet AMD and DME.

As we near top line data for our Phase III wet AMD program, it's worth remembering the key elements underpinning its thoughtful design. Our approach is derisked, following an established non-inferiority regulatory pathway. Both pivotal trials are identical and compared DURAVYU to on-label 2-milligram aflibercept, which is intended to reflect real-world practice and generate clinically-relevant data to inform the retina community.

Additionally, both trials are evaluating 6-month redosing and statistical superiority in treatment burden reduction to support the potential for a compelling label that addresses the need for effective, durable disease control. Taken together, we believe our Phase III program is well positioned to deliver data that will build upon our positive clinical development track record and contribute to strong commercial positioning for DURAVYU, if approved. We look forward to reporting top line data from our Phase III wet AMD trial, LUGANO, this summer with our second trial, LUCIA to follow shortly thereafter.

We are applying the same derisked approach to our Phase III DME program, which leverages a non-inferiority design, an on-label 2-milligram aflibercept control, and redosing every 6 months. Similar to our wet AMD program, we designed our pivotal trials for DME based on impressive data from the Phase II VERONA study in which DURAVYU demonstrated rapid efficacy with 4 to 5 letters of vision improvement and approximately 50-micron improvement in anatomic control compared to aflibercept at week 4.

Both of our DME trials, COMO and CAPRI are now underway with over 1/3 of patients enrolled across both trials following first patient dosing at the end of February of this year. Our strong pace of enrollment is driven by our ability to leverage our pre-existing clinical trial infrastructure and investigator network as well as the significantly smaller trial size compared to our wet AMD program. We expect top line data in the second half of 2027.

Stepping back, both wet AMD and DME together represent the vast majority of the global branded retinal disease treatment market with a combined branded opportunity totaling nearly $15 billion in the U.S. and growing. Through exceptional clinical leadership and commitment to serving the retinal community, we are positioning DURAVYU to become a durable franchise with blockbuster potential.

With a unique multi-MOA, robust clinical data package, proven delivery technology, the ability to be shipped and stored at ambient temperatures and administration via standard in-office intravitreal injection, DURAVYU represents a compelling and truly innovative product profile that has the potential to reshape the treatment paradigm for serious retinal diseases. We continue to make significant strides in our commercial readiness while remaining disciplined in our investments as we prepare for regulatory submission.

We have thoughtfully grown our organization with the addition of Michael Campbell as Chief Commercial Officer last quarter. In addition to expansion across key areas such as marketing and market access, regulatory, compliance and medical affairs to build on our organizational capabilities as we advance our launch planning and strategy for DURAVYU in wet AMD.

In addition to progress on our commercial readiness activities, we continue to prioritize CMC readiness. Our cGMP facility in Northbridge, Massachusetts has been online for over a year, supporting our plans for an anticipated CMC submission for our potential new drug application or NDA as well as for commercial supply, if approved. We continue to prepare for pre-approval inspection, underscoring our growing independent commercial readiness that we believe will ensure our preparedness to deliver DURAVYU to patients upon potential approval.

Before passing it over to George to review the financials, I'd like to thank the entire EyePoint team for your unwavering commitment to improving the quality of retinal care. We are proud to support the retina community and grateful to the patients, study coordinators and clinical investigators who enable our research. We look forward to our upcoming Phase III wet AMD readouts together with continued progress in our DME program, which we believe sets the stage for meaningful value creation at EyePoint.

I will now turn the call over to George.

Thank you, Jay. As the financial results for the 3 months ended March 31, 2026, were included in the press release issued this morning, my comments today will be focused on a high-level review for the quarter. Importantly, we continued our disciplined financial management and good stewardship of our resources, ending the first quarter with $223 million in cash and investments.

For the quarter ended March 31, 2026, total net revenue was $0.7 million compared to $24.5 million for the quarter ended March 31, 2025. The decrease was primarily driven by the recognition of remaining deferred revenue related to the company's agreement in the second quarter of 2023 for the license of YUTIQ product rights.

Operating expenses for the quarter ended March 31, 2026, totaled $88 million compared to $73 million in the prior year period. This increase was primarily driven by the ongoing Phase III trials for DURAVYU in both wet AMD and DME and the scaleup of our Northbridge commercial manufacturing facility.

Net non-operating income totaled $2 million and net loss was $85 million or $0.99 per share compared to a net loss of $45 million or $0.65 per share for the prior year period. As I noted earlier, cash, cash equivalents and investments in marketable securities on March 31, 2026, totaled $223 million compared to $306 million as of December 31, 2025.

We continue to expect that our current cash position will enable us to fund operations into the fourth quarter of 2027 beyond key milestones for the Phase III wet AMD program expected later this year.

In conclusion, we're pleased with EyePoint's progress so far in 2026 and remain well capitalized to deliver DURAVYU through key value-driving milestones in the 2 largest retinal disease markets.

I will now turn the call back over to Jay for closing remarks.

Thank you, George. As we continue to deliver on our key priorities for 2026, our team is focused on advancing preparations for the pivotal Phase III top line data readout in wet AMD expected mid-year and completing enrollment of our Phase III DME program in the third quarter of this year.

We believe TKIs represent the next frontier in retinal disease innovation, and we are proud to be advancing DURAVYU as a potential first and best-in-class option in the 2 largest retinal disease markets.

Thank you all for your attention this morning. I will now turn the call back over to the operator for questions.

[Operator Instructions] Our first question comes from the line of Tess Romero with JPMorgan.

So just one from us, on the DME side, actually. So for your COMO and CAPRI trials, you talked a bit about your swift pace of enrollment here. Can you speak to what you're hearing from the investigators in terms of the level of interest from both patients and physicians around a TKI sustained delivery treatment option like DURAVYU? What are the key differences and similarities that you hear in the DME space versus maybe what you heard in the wet AMD space?

Thanks for the question, Tess. Given that our CMO, Ramiro Ribeiro, is really at the forefront of this, I'll ask him to answer your question.

Tess, thanks for the question. So first, as you mentioned, we are seeing a great excitement around our DME program, COMO and CAPRI with a quite quick enrollment so far. We are now leveraging all the infrastructure that we use for our wet AMD with our clinical sites and our CRO and vendor as well.

The feedback that we're getting from the investigators, very similar to our wet AMD, is that our study is a very patient-centric study, trying to address a very important unmet need, which is the treatment burden. So patients that are participating in this study are very excited for a therapy that can last for about 6 months.

In particular, for the DME indication, we know that the need for this patient population might be even greater than wet AMD. This is a patient population that is relatively younger, and they are still in the workplace. So a therapy that can reduce the number of visits like DURAVYU is, of course, of very interest for this patient population. Again, I think the excitement both from the investigators, the patient in clinical sites is being reflected in the pace of our enrollment.

And I'd like to add just one more thought to this. We invited 90 of our wet AMD investigators to be investigators in the DME trials and all 90 accepted. So we believe that continues to show investigators' enthusiasm for the potential of DURAVYU.

Our next question comes from the line of Yigal Nochomovitz with Citigroup.

I'm just wondering if you could comment on how the supplement trigger criteria are functioning in the Phase III trial relative to the Phase II trial, the DAVIO 2 trial? And if you could also comment on what you would expect to be a meaningful supplement rate in the Phase III trial that would be consistent with a strong commercial uptake.

Yigal, nice to hear from you. Thanks for the question. With respect to supplements, I'm going to have Ramiro comment in a moment about how that is working in the trial. But I think there's really 2 issues around the supplementation that people should understand. The first is that in the clinical trials, supplements will be handled statistically with sensitivity analyses that we will be doing when we submit the NDA.

So there is a rate of supplements, at least conceivably, above which the drug would not be considered to be working independently because of the high rate of supplements. In saying that, the FDA has never put a line in the sand as to what that level would be, because they want to see the totality of the data. They want to see the safety and the efficacy otherwise.

So, from a supplementation perspective, there is an important hurdle, which, of course, we need to get over, which is the non-inferior margin, which is the primary endpoint. If we are approved, then I think the commercial acceptance shifts to a very different place.

In the real world, a supplement is not a failure. Doctors, I believe, if we are approved, will enjoy taking advantage of using 2 MOAs to help a [indiscernible] across a lot of chronic diseases, where if 2 MOAs in treatment are available, using them synergistically is a potential advantage to patients. Now obviously, we haven't shown that yet in our trials, but we hope that, that would be the case for the benefit of patients.

But my point about supplements in the real world, I'll give you again an example. If I've got a patient that I have to inject every 2 months with a biologic anti-VEGF and let's hypothesize that DURAVYU is FDA approved, it's safe, it's tolerable. It has a label for every 6 months and the patient gets shifted to DURAVYU, for the next year with 2 injections. But in addition, they received 2 injections of a biologic.

Well, it's a great win for everyone. The patient can go from every 2 months to every 3 months from 6 injections to 4 injections and that presumably the advantages of DURAVYU will be aligned with the patient and the doctor's interest. So there is the regulatory hurdle that needs to be reached over supplements. And if that's reached, I believe that supplementation in the real world will have great latitude for acceptance.

Okay. And then if I could just ask one other follow-up on DME. Of course, you mentioned IL-6 as a potentially interesting biomarker. Are any of those IL-6 biomarker endpoints formally embedded in the Phase III DME program as sort of secondary endpoints that could help differentiate the product?

I would say yes, but indirectly. Given that there is no way to measure in a patient in a clinical trial, the direct effects on IL-6 or JAK1, we would be measuring the indirect effects. The indirect effects, of course, number one is visual acuity. What we hope to be doing in the long term is provide better visual acuity for patients. But in DME, we may be able to provide it in the short term.

Again, looking at the VERONA data at week 4, the patients who received DURAVYU had better vision and drier retinas as early as week 4 compared to a single dose of aflibercept. We have set up the COMO and CAPRI trials to try to show that. And there is a secondary endpoint of visual acuity and OCT at week 4, given our drug is given at day 1 in the DME trials so that -- we hope to show that even if we're non-inferior and equivalent to Eylea, but we can provide the benefit earlier with fewer injections, then we will be able to have a great advantage to patients and therefore, a commercial success.

There are other secondary endpoints that we can look at that are not direct measurements of IL-6 or JAK inhibition. For example, leakage on fluorescein angiography. And you may recall that in the VERONA trial, we had a significant reduction in leakage as measured by an independent reading center, and it was dose-dependent, with the higher dose of 2.7 milligrams showing much greater leakage reduction compared to the lower dose and compared to the aflibercept control. And that is the kind of secondary endpoint that if we can show reduction in leakage greater than aflibercept, I think the evidence would lead to that is due to IL-6 inhibition.

Our next question comes from the line of Faisal Khurshid with Jefferies.

I just wanted to ask on the ongoing wet AMD studies, are you guys able to see blinded rescue rates? And are those tracking in line with your expectations?

Thanks for the question, Faisal. Again, I'll let Ramiro talk about the supplementations and what we're seeing and what we're not seeing.

Faisal, thanks for the question. We -- there's a very small team at EyePoint that reviews the supplementation injections essentially to make sure that the clinical sites are following the protocol. But we don't review aggregated supplemental injection rate, and that's something that we don't disclose publicly.

And if I may add, we -- again, as Ramiro indicated, have no insight into the number of supplements, supplementation rate, et cetera, at this point. It's all masked. But we do anticipate that the supplementation rates in the Phase III trials will be less than what we saw in the Phase II for several reasons, again, due to the tightening of the supplement criteria, getting rid of the physician discretion in supplements, the reinjection at month 6 and the inclusion of the majority of naive patients, all of those together should result in fewer supplements in Phase III.

Our next question comes from the line of Yatin Suneja with Guggenheim.

I'm sorry. This is Eddie on for Yatin. Thinking about the fixed-dose regimen that you guys are going after, are patients who are already dry with stable vision still receiving that third dose at week 56? And if so, is there any incremental safety signal from redosing well-controlled patients? And further, has the FDA weighed in on how this complicates the retreatment redosing schedule?

Thanks, Eddie. Very good question. And yes, this is a fixed dose regimen. It has nothing to do with whether the patient at the time of their repeat dose of DURAVYU is dry or wet or what the visual acuities are. So just like any drug, for example, take 2-milligram Eylea, when it was first studied every 2 months, that was fixed dose where they received that injection, whether they were active or not. So that's going to be true in our trial.

From the perspective of safety, we've done extensive preclinical safety in animals. And in rabbits, we never found a maximally tolerated dose of vorolanib, and we've injected scale dose of about 10x higher than anything we could achieve in humans. We've also not found the maximally tolerated number of inserts in rabbits. And so from a safety perspective, we were not concerned about reinjection. Again, we are reviewing the masked safety. And I will once again turn to Ramiro if he wants to comment on the upcoming DMC meeting that is going to be occurring shortly.

Yes. No, thanks, and thanks, Eddie, for the question. We -- as Jay mentioned, safety is something that is, of course, paramount for EyePoint, and we conduct ongoing safety review of the data. If you do the math, we have now have patients that reached that week 56 visit that you mentioned, which is the third dose of EYP-1901, and we haven't seen anything different than what we saw before. We do have an upcoming DMC meeting in the month of May, where the members will review our masked data, and we look forward to provide updates after that meeting.

Our next question comes from the line of Debanjana Chatterjee with Jones.

So what have you seen in the masked safety data set so far? And has anything shifted your expectations going into the DSMB review that is scheduled for late May?

Thanks for the question, Debanjana. And we're not commenting on any individual SAEs or AEs. But in total, I would say and repeat what Ramiro has said, what we've seen so far is consistent with what we have seen in the prior 4 trials. No new safety concerns and no incidents that we haven't seen or expected from before. Again, Ramiro, I don't know if you want to add any more color to what I said.

Yes. No, I think just again, to reiterate, safety at EyePoint is paramount. We -- internally, we review the data on an ongoing basis on a masked fashion. And as Jay mentioned, we have no safety signal. We haven't attacked anything that is new. The safety profile continues to be very similar to what we saw in our previous completed studies.

Just a very quick follow-up. Can we expect any formal public update following the DSMB meeting?

Yes. I think it's likely that we will give an update, yes.

Our next question comes from the line of Lisa Walter with RBC Capital Markets.

Congrats on the progress. We have seen a long-acting TKI competitor had a successful readout of their pivotal study earlier this year. And we've heard their plan is to file with the FDA and seek approval on this trial alone. In a scenario where essentially both, yours and the other long-acting TKI, are being launched within similar time frames, does perhaps having 2 products with the same mechanism of action actually help break into a market which already has an established therapeutic base with the anti-VEGF? How should we think about this?

Yes, Lisa, thanks for the question. It's a great question. And I think you've really hit on a very important point. This is not a zero-sum game. The TKIs are going into a multibillion-dollar market. And there is certainly room for 2 competitors to both be very successful in this very large market. There is evidence from -- as I think you're alluding to, from other launches with new mechanism of action into an established space that having more than one entry really helps both because doctors are hearing it and learning about it from multiple places. So we welcome another competitor. And part of that is we believe we've got a better drug and a better delivery system. And hopefully, if both are FDA approved, well we will have the opportunity from a commercial basis to really show that.

Our next question comes from the line of Nick for Colleen Kusy with Baird.

It's Nick on for Colleen. So just at ARVO and other recent scientific conferences, just wanted to ask what -- just what the takeaways were on DURAVYU, sentiment among physicians and if you got any learnings about how physicians intend on using DURAVYU upon a potential approval?

So one point I'd like to make, and thanks for the question, Nick. One point I'd like to make about ARVO is we had a poster there, which showed another preclinical model of leakage induced by VEGF and IL-6. And in that model, vorolanib, the active ingredient in EYP-1901 was able to suppress the inflammation induced by IL-6 and VEGF equal to an anti-VEGF and an anti-IL-6.

So again, one more model that suggests that vorolanib does have potent anti-IL-6 activity through the JAK1 receptor. There was a lot of interest in that poster. A lot of KOLs saw it, and there were quite a number of comments. Ramiro met with multiple KOLs at ARVO, and I will let him weigh in on what the sentiment seems to be around EYP-1901.

Yes. No, thanks, Nick, for the question. And we had a very productive ARVO this year with several posters being presented, including the one that Jay just mentioned. We also had a few advisory boards and some interactions with our Phase III wet AMD and DME investigators. I think first on the sentiment of the clinical trials, I think everybody, of course, is very excited for the upcoming data for LUGANO and LUCIA. Mentions are, this is going to be the highlight of the retina space for the year of 2026.

For DME, the investigators, again, reflect that this is a really well-studied plan, very patient-centric, and they were all excited about bringing the therapy for patients with DME. In terms of future use of DURAVYU, as Jay mentioned previously in the call, they expressed the important unmet need that we're trying to address with DURAVYU. And they see this if we can replicate the results that we saw in the Phase II study as something that is going to be very meaningful for patients, especially for those patients that require frequent treatment.

Our next question will be coming from the line of Yale Jen with Laidlaw.

And I just follow up a little bit on the commercial question earlier, which is that besides the TKIs, in terms of the long-acting biologics, VABYSMO and the high-dose Eylea, which one you think you [ scale really ], if approved, will be competing more or less? And any comment on that?

Thanks for the question, Yale. It's an important question because these are excellent medications that are multibillion-dollar drugs that are really helping many, many patients. I think the first point to be clear on is we're not another anti-VEGF biologic. We work at the receptor level. We have multi-MOA block VEGF, PDGF, and we do believe the inflammation related to IL-6 elevation, which is not something that they do.

In addition, it looks like from our Phase II data that at least 2/3 of the wet AMD population could be treated with our drug alone every 6 months should physicians choose to do that. That's not something that we're seeing in the real world with those new medications. While there are extended durations, what the real-world data is suggesting that most patients are getting about a week or 2 extension from either of those drugs compared to what they were on before.

Now that's great, but we still believe that it leaves a lot of room in the market for a 6-month or longer medication. I -- it's hard to predict which of those drugs will be -- I don't want to say the winner because I think both drugs are doing well when we launch potentially. But we -- again, our belief is that we can provide benefits greater than what either of those drugs can do for patients. And we believe in the long term, we will achieve better visual acuity.

Mike Campbell, our Chief Commercial Officer, I believe, is on the line. And I don't know if he's going to maybe have any other comments now. I think it's a little early to talk about commercial strategy. But maybe, Mike, you can talk a little bit about how you view the competition.

Yes. Thank you for the question. The one point I would add is that while we have these very good anti-VEGFs, longer-acting anti-VEGFs in the market, not only is the real-world data showing the extension that Jay mentioned around 8 days. We also look at what the retina specialists are saying in the community and where the needs are.

And so if you look at the American Society of Retina Specialists, ASRS, every year, they put out a PAT survey. And very consistently, the #1 need in wet AMD treatments that is reported from ASRS is still durability even with VABYSMO and Eylea HD in the market. So to Jay's point, there is a very clear opportunity should DURAVYU be successful and be approved, there's a very clear opportunity or room in this market for more durable agents.

Our next question comes from the line of Samuel Rollenhagen with TD Cowen.

This is Sam on for Tara. Can you hear me?

Yes.

Congrats on another great enrollment update. So I just wanted to ask on safety for the LUGANO data. And if you could help us set some expectations there for what you're hoping to see. I guess, besides avoiding some of the more serious back of the eye events, are there any other AEs where you think DURAVYU could be differentiated versus competitors? And then also, it'd just be great if you could clarify how you're anticipating to disclose those safety data in the top line release? Will you be reporting all events or just those above a specific threshold?

Thanks for the question, Sam. And so again, the -- one of the hallmarks of the current anti-VEGF approved drugs with perhaps one exception, is they're quite safe. And while patients and physicians will probably be willing to accept perhaps a few more AEs from a long-acting drug, there can't be a big difference. There's really a high bar that's out there for safety. And the good news is that all our safety from our 4 reported trials shows no real increase in any SAE or AE that would preclude our drug from being widely accepted, in our opinion.

So from a safety perspective, again, a lot of the safety issues that can occur are injection related. And if you're reducing the number of injections that a patient gets, then you're likely in the long term to have fewer adverse events. We hope to be able to show that in our pivotal trials. And from a reporting perspective, I don't know how granular the safety reporting will be initially, but we do expect to have complete AE tables when we present the data from LUGANO and LUCIA.

I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program, and you may now disconnect. Everyone, have a great day.

Morning. My name is Michelle, and I'll be your conference operator and recent corporate development conference call. There will be a question-and-answer session to flow at the completion of the prepared remarks. Please be advised that today's conference is being recorded at the company's request.

I would now like to turn the call over to Greg Elston, Executive Vice President and Chief Financial Officer of EyePoint. Sir. Please go ahead.

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's Fourth Quarter and Full Year 2025 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer of EyePoint. Jay will begin with a review of recent corporate updates and discuss our clinical programs for DuraView and wet AMD and DME. I will close with commentary on the fourth quarter and full year 2025 financial results. .

We will then open the call for your questions where we will be joined by Dr. Ramiro Robero, our Chief Medical Officer; and Mike Campbell, our new Chief Commercial Officer. Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of the release can be found in the Investor Relations tab on the company website, www.eyepoint.bio.

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, financial projections and our plans and prospects.

Actual results made materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we have made or may make with the SEC in the future. Any forward-looking statements represent our views as of today only.

While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of EyePoint.

Thank you, George. Good morning, everyone, and thank you for joining us. 2025 was defined by significant progress and achievement for EyePoint as we made important advances that set the stage for success and potential value creation for the year ahead. As a result of our exceptional clinical execution, driven by our derisked and patient-centric programs, our lead asset, DURAVYU, is on track to deliver top line data in wet age-related macular degeneration, or wet AMD, beginning in mid-2026. We -- in parallel, we advanced DURAVYU as the only tyrosine kinase inhibitor or TKI program in diabetic macular edema, or DME.

We are pleased to report that as of last week, the first patients were dosed in both pivotal Phase III in trials with a strong cash position that is expected to fund operations into the fourth quarter of 2027 and multiple inflection points on the near-term horizon, we are entering a transformative period for EyePoint with significant momentum.

Our conviction in DURAVYU blockbuster potential is underpinned, first and foremost, by its compelling clinical profile, and our Phase II trials in the largest retinal disease markets. A single dose of DURAVYU demonstrated durable efficacy with improved vision and tight anatomical control. Importantly, DURAVYU has a favorable safety profile with no safety signals in over 190 patients across 4 completed clinical trials.

The safety trial so far remains consistent in the ongoing Phase III Lugano and Lucia trials for wet AMD based on continued masked internal safety review and two interim reviews conducted by the independent Data Safety Monitoring Committee. In addition to its robust clinical profile, we continue to believe that the potential for every 6-month dosing the standard in-office intravitreal injection, a best-in-class delivery technology and a novel multi MOA that inhibits VEGF, PDGF and IL-6 via the JAK1 receptor with no tie 2 inhibition are the key drivers of its differentiated profile.

This unique profile positions DURAVYU to address both VEGF-mediated vascular leakage and IL-6 mediated inflammation that contribute to disease pathogenesis in wet AMD and DME, thereby potentially enabling improved long-term outcomes for patients with fewer injections. Our confidence is also grounded in our established and clinically rigorous approach through outdoor reviews development. Our Phase III wet MD program was intentionally designed to inform real-world practice and generate meaningful data for the retinal community by comparing DURAVYU to on-label aflibercept as the control.

Additionally, we will be evaluating statistical or in treatment burden reduction and 6-month redosing to support a compelling and relevant label. Based on the success of our large Phase II DBO 2 trial and with our proven regulatory pathway and strong execution to date, we believe our wet AMD program is uniquely derisked and optimized to support success. We look forward to reporting top line data beginning in mid-2026.

The clinical and regulatory rigor that defines our approach also extends beyond Wet MD as we work to position DURAVYU for multiple indications. We are pleased that randomization is now underway for both COMO and CAPRI, our two pivotal Phase III trials in DME where we expect to drive rapid enrollment by leveraging our pre-existing clinical trial infrastructure and investigator network.

In line with our wet AMD program, our DME program follows an established non-inferiority design with an on-label standard of care control and redosing every 6 months. It was similarly informed by impressive Phase II data from the VERONA trial where eye treated with DURAVYU demonstrated meaningful visual and anatomic improvements as early as 4 weeks. We anticipate top line data in the second half of 2027 and look forward to building upon our strong track record of clinical execution as we advance DURAVYU through our Phase III DME program.

We believe that DURAVYU is well positioned to be the first to market among all current investigational sustained release programs in both wet AMD and DME, with a potential best-in-class profile, and we remain focused on building DURAVYU into a durable franchise, targeting the largest retinal disease markets. With the combined current global market of $10 billion and growing, wet AMD and DME make up the vast majority of the global branded retinal disease market.

DURAVYU's unique MOA, robust clinical data package, proven release technology and attractive storage and administration benefits offer a compelling value proposition that we believe will address the long-standing need for innovation and support strong commercial positioning. As part of our ongoing commercial readiness efforts, we are thrilled to welcome Michael Campbell as our new Chief Commercial Officer. Mike is a seasoned commercial leader with a proven track record of successful product launches and oversight of prominent ophthalmology franchises, including Lucentis and Xiidra. As we prepare to deliver on EyePoint's next milestones, including potential approval and transformation into a fully integrated commercial organization, Michael's deep commercial expertise will be instrumental as we position to review for a successful U.S. launch.

In addition to strengthening our commercial leadership we continue to expand operations at our 41,000 square foot CGMP manufacturing facility in Northbridge, Massachusetts. The facility has been online for over a year, supported by about 60 full-time employees and continues to not only support the CMC submission for a planned new drug application, or NDA, but also commercial supply.

As we near regulatory submission, we are preparing for preapproval inspection, underscoring our growing independent commercial readiness and commitment to ensuring that we are well equipped to deliver DURAVYU to patients if approved. Before passing it over to George to review our financials, I'd like to thank the entire EyePoint team for your continued dedication to improving vision and patient outcomes.

We are proud to advance our therapeutics for the benefit of the entire retina community and grateful to the patients, study coordinators and clinical investigators who make our research possible. As we look ahead, we are excited about the upcoming milestones and the opportunities in store for us to extend our leadership and sustained ocular drug delivery. I will now turn the call over to George.

Thank you, Jay. We ended 2025 with a strong balance sheet of $306 million in cash and investments, driven by continued stewardship of our resources and $173 million follow-on financing in October. As the financial results for the 3 months and full year ended December 31, 2025, were included in the press release this morning, my comments today will be focused on a high-level review of the quarter.

For the quarter ended December 31, 2025, total net revenue was $0.6 million compared to $11.6 million for the quarter ended December 31, 2024. The decrease was primarily driven by recognition of remaining deferred revenue related to the company's agreement for the license of YUTIQ product rights in the second quarter of 2023. Operating expenses for the quarter ended December 31, 2025, totaled $71 million compared to $57 million in the prior year period. This increase was primarily driven by the ongoing Phase III trials for DuRaVie and wet AMD and DME.

Net nonoperating income totaled $3 million and net loss of approximately $68 million or $0.81 per share compared to a net loss of $41 million or $0.64 per share for the prior year period. Turning to the full year ended December 31, 2025. Total net revenue was $31 million compared to $43 million for the year ended December 31, 2024. The decrease was primarily driven by the recognition of remaining deferred revenue related to the company's agreement for the license of YUTIQ product rights in the second quarter of 2023. We Operating expenses for the full year ended December 31, 2025, totaled $275 million versus $189 million in the prior year period. This increase was primarily driven by the ongoing Phase III trials for DRIVE and wet AMD and DME.

Net nonoperating income totaled $12 million and net loss was $232 million or $3.17 per share compared to a net loss of $131 million or $2.32 per share for the prior year period. Cash and investments on December 31, 2025, and totaled $306 million compared to $371 million as of December 31, 2024. We expect the cash and investments on December 31, 2025, and will enable us to fund operations into the fourth quarter of 2027, well beyond key milestones and NDA preparation for the Phase III wet AMD program in 2026 and fully funding the Phase III pivotal DME program. In conclusion, we are incredibly pleased with EyePoint's progress in 2025 and are well capitalized to continue advancing Du Review through both of our late-stage development programs. I will now turn the call back over to Jay for closing remarks.

Thank you, George. EyePoint's progress in 2025 reflects the strength of our programs and our consistent execution. As we prepare to drive value through transformative catalysts in 2026, we will continue to be guided by our derisked clinically rigorous and patient-centric approach. We are well positioned to deliver on our near-term priorities, including reporting top line data for the Phase III LUGANO trial anticipated in mid-2026, with LUCIA data to closely follow, Completing enrollment in our pivotal Phase III DME program in the second half of 2026 and preparing for regulatory filing in wet AMD, assuming positive Phase III data. Thank you all for your attention this morning. I'll now turn the call over to the operator for questions. .

[Operator Instructions] Our first question is going to come from the line of Talmer with JPMorgan.

Jay, George, can you clarify the rate of ocular AEs that you have seen across your cumulative safety database with DURAVYU, in particular, around the incidence of victorious floaters and cataracts -- and then relatedly, what specifically has the physician feedback been around your safety profile?

Sure, Jess. Happy to address that. As you probably recall, we've treated over 190 patients in completed trials, that's 1 Phase I and 3 Phase II trials. And the number of cataracts that were measured by the investigators in those 191 patients is 5.8%. In contrast, -- if you just look at the AVO 2 data, the cataracts in the DAVIO-2 study in the study arms was approximately 8% and -- in the EYLEA control arm, it was numerically higher. It was -- so this is an elderly population you do expect cataracts.

But of course, in the controlled AVIO II trial, there was no mismatch between the cataracts at all. With respect to try floaters, once again in the entire population, 5.2% of the Drive patients reported floaters which is, again, consistent with what you might see in any type of study that has injections into the eye. So I think to answer the second part of the question, which is how do the clinicians perceive it. I think 1 of the main reasons that we were able to enroll the Wet MD trial so rapidly is the doctors had a really good Phase II data to evaluate both the efficacy and the safety of our drug.

And I think that gave them a great confidence in enrolling patients. I think, again, I'd like to make one more note on safety and efficacy. We think of visual acuity as the primary efficacy endpoint, which it is for all of these studies, but visual acuity also is a safety outcome. And again, just to remind the listeners in the DAVIO 2 trial, are treated patients in wet AMD gained vision. And in fact, in the unsupplemented isen DAVIO 2 trial, the treatment arms gained 2.1 letters over the course of the trial, which is actually numerically greater than the EYLEA arm gained learn at that point was getting 3 injections over that time frame because it was on label EYLEA. So that to summarize, we're very comfortable with our safety. We've had no ocular or systemic SAEs attributed to our drug. And in those 4 prior trials, no safety signals.

Our next question comes from the line of Yatin Suneja with Guggenheim.

Just a quick one on the regulatory front. Just love to hear from you how are you thinking about recent sort of FDA chatter around single study driven regulatory approvals. Does that change your strategy just as curious what is possible? And then Jay, I appreciate your comment on the safety clearly has been pretty good across Phase II studies and also Phase III blinded review that you have provided. Anything on opacity that you can comment like how are those numbers relative to what we see with other TKIs in development? .

Thanks for the question, Yatin. So for the first question, the regulatory yes, I think in general, we would all welcome a more rapid and less expensive pathway to drug approvals. But as you heard this morning, and as most listeners know, we have 2 identical Phase III wet MD trials underway that are reading out this year. If in fact, the FDA would allow us to file with a single trial. Our second trial is only 2 months behind. And so overall, I don't know that, that would give us any particular advantage in a single trial.

In DME, we have 2 simultaneous trials that we expect to read out in the fourth quarter of 2027. And given that other regulatory agencies around the world are probably still not aligned with a single trial. We don't believe we have any reason to alter our approach for these 2 indications. Future indications, of course, we will discuss with the agency.

With respect to single trial in retina studies, I think that it's certainly something the agency may be considering in the future. Of course, the rules around single trial filing that the FDA updated in 2023. Those rules are already out there. And in order to do that, you not only need to have a large trial, but you need confirmatory evidence that your drug is active if it's single trial. Of course, in the case of rare diseases, there are exceptions that are made. But wet AMD, DME, unfortunately, are not rare diseases.

So with regard to the regulatory pathway, we think our pathway is derisked. We have taken the non-inferior approach, which is the approach essentially the 5 of the last approvals have taken, and we've got 2 trials in each of those large indications already in motion. With respect back to safety for a second. Opacity is a sign that the mass investigator can see when they look into an eye. They see if there's a blockage in their ability to look into the eye, either in the back of the eye in the vitreous or the front of the inter chamber. In our DAVIO 2 trial, we had about a 1% rate of vitreous capacity.

We had no rates of antechamber opacity. That has not been seen at all with DURAVYU in any of the treated eyes. And we wouldn't have expected it. DURAVYU is designed to hold the drug until the drug is fully eluted. So we have no free floating drug particles. We've had not seen any migration of the inserts, so far at least have not been reported in humans to break up into pieces. They just slowly buy or road and release their payload, which again, I'd like to mind everybody, our scientists have been able to upgrade the insert so that they're 94% payload, they're only 6% matrix. So we haven't seen any antigen capacity, and we wouldn't expect to in the vitreous capacity percentage is low.

Our next question comes from the line of Yigal Nochomovitz with Citigroup.

I'm just curious with regard to the conduct of the wet AMD trials before they read out this summer and into the early fall. Will there be additional looks at mass safety what will the cadence of those be? And will you be reporting that to us as you proceed.

Thanks, Yigal. We've got Romero on the line, our CMO. So Romero feel free to answer that question about continued safety looks in the WMD trials.

Good to hear from you. So we have, as a safety monitoring body for the studies, both internal mass review that we do as an ongoing basis as well as the independent data monitoring committee that reviews the unmasked data. The last DMC meeting was in November. At that point, they reviewed the data from patients. And I remind you that at that point, we had over 25% of patients getting the second dose. The safety profile of DURAVYU so far has been consistent with our previous experience in the Phase I, Phase II studies with nothing near to be aware. Our next DMC meeting is scheduled in May. So that's going to be the next opportunity for that group of physicians to review the MS data and provide updates to us. .

And just 1 question on biomark because I know you identified IL-6 recently. I'm just wondering what additional biomarker work may you be doing to further explore the the activity profile overall? .

Yigal, thanks for that question. Additional biomarker work around the JAK1 receptor and its ability to block downstream effects of IL-6. We will have additional data on that that we're presenting at ARVO in May, we have additional ongoing diet really try to assess the impact of that in humans. With respect to the rest of the potential receptors, we did a very extensive evaluation of the kinome last summer at the time that we discovered that vorolanib was a potent inhibitor of JAK1 with an IC50 of about 80nm and we didn't discover at the time any or significant receptors involved in retinal disease, either positively or negatively that Verolme was active against. .

Our next question will come from the line of Clara Dong with Jefferies.

So just in terms of the durable multi-genic profile beyond the VDFinhivision. So how prominently do you expect this mechanistic differentiation to really be featured in your regulatory discussions and maybe eventual commercial messaging as well? And is there any plan for you to report more preclinical evidence of the IL-6 inhibition In the future? .

Yes, Clara, great question. Thanks for it. And a bit complicated because the story, I think, is still unfolding. Ultimately, what we all want is better visual acuity. -- our patients certainly and the physicians who treat them. And so the great thing about what we do is eventually, it's all about the data. And what we hope to show -- and really, if we can show it, I think, primarily in our DME trials is that, that additional IL-6 blockage does give a more rapid onset of visual acuity improvement. That's what we showed in the Verona data. If you recall, as early as week 4, the treatment arms with Derive had already separated from EYLEA. .

We were already 4 to 5 letters better in about 40 microns drier than EYLEA. And we believe most likely that's the effect of the IL-6.

IL-6 has also been implicated in wet AMD. I think it may be perhaps a little more difficult to winnow out the effects of in the wet AMD population, but I certainly wouldn't rule out that we might end up with better visual acuity in the wet AMD population overall. Again, I mentioned earlier with respect to subgroup analyses, the subgroup in W-2 that was not rescued ended up with slightly better vision than on-label EYLEA. With respect to regulatory, I'm going to let Ramiro take a stab at that. And with respect to commercial, Mike Campbell's here, and maybe Mike can try to take a stab at how that might affect us commercially. Ramiro, why don't you go ahead first?

Yes, sure. Thanks, Clara, for that question. So the regulatory path that we're following with both the wet and the DME studies, is a noninferiority approach. So if we show that BCVA are similar to the control arm that, of course, might be sufficient for regulatory agencies. With that, for both DME study as part of our analysis plan and hire testing, we are going to be testing for CDA. And as Jay mentioned, there are a body of evidence suggesting that IL-6 has a role in both DME as well as warm. So we're going to be investigating that in our Phase III clinical studies.

And Mike, if we're able to show this additional benefit of IL-6, can you perhaps comment on the commercial aspects of that? .

Yes. Thank you, Jay. And the commercial approach, specifically with visual acuity and safety and as Jay mentioned, our unique MLA, gives us a real opportunity here with IL-6 as part of that. complete package. I mean the messaging around this and the opportunity to commercialize gives patients and providers a real opportunity potentially to have a best-in-class durable approach to treating wet AMD and DME. .

As mentioned, if there's an opportunity to be able to show the benefit of IL-6 in the DME population that has a real meaningful commercial opportunity to really separate yourself in the marketplace.

Our next question will come from the line of Greg Suvanovich with Mizuho.

Congrats on the first dosing in your DME Phase III studies. Maybe a question for Mike as the new Chief Commercial Officer, as you come into the company, how are you thinking about commercial prep for the potential launch of DURAVYU, what are the key steps that are needed at EyePoint over like the next 6, 12, 18 months to ensure an optimal U.S. commercial launch, especially when you might be going head-to-head in the competitive landscape versus another competitor.

Go ahead, Mike.

Yes. Thank you, Greg. There is a complete go-to-market strategy and approach for sure. And as we think about the opportunity here, and, to your point, potentially even having a competitor in the marketplace, there's a lot of precision that goes into a market approach, especially in the specialty retina marketplace. So it's areas, for example, around not only positioning and messaging the market search, the pricing research. All of that is priority along with patient access services.

I mean we can have a fantastic and we believe we will have a fantastic opportunity here. But if you can't really get good at allowing patient access through coverage and reimbursement then it can really hinder you. And so there's a lot of effort that we're putting behind making sure we have the right rigor to come to market and make it easy for doctors to be able to DURAVYU, but also easy for patients to access DURAVYU.

And just lastly, I would also add that there's a lot of really good work that is going on and will continue to go on around coverage with payers and good payer research that we've done.

And Jay, if I could just quickly follow up your Phase III trial designs in DME are just slightly tweaked or different from the Phase III trial designs in wet AMD. Just wondering if you could point us to reasons why they're slightly different in terms of kind of loading doses, maybe maintenance doses, just things like that.

Sure. Go ahead, Ramiro.

Yes, Greg. Thanks for the question. So when we look at our DME study in comparison to our WebMD program, there are 2 main differences. The first 1 is on the control arm. For nonfert studies, the FDA mandate that we use own label medication and the own-label regimen for fibercept in DME is 5 loading dose, followed by every 8 weeks. So that's how we're going to be dosing patients in the control arm. The other difference is that for the DME study, we are now dosing review at day 1. If you recall from the wet AMD study, we actually dosed to a view after the reloading dose at week 8.

The reason for doing what we're doing in the DME study, which is to dose at a 1 is to try to replicate the findings that we had in our Phase III study. If you recall from Phase III study, we dose patients on day 1 with a fibroses review compared to fibers alone. And then in that study, we show a greater improvement in the CBA in CSD early on in the study at week 4. So -- and we believe one of the reasons it could be because of the role of IL-6 JAK1 in the DME disease. So we believe that if we can replicate those findings in the Phase III study, providing patients an earlier improvement in the CB and CST is going to be something that is going to be advantageous for our patients.

Our next question comes from the line of Debanjana Chatterjee with Jones.

One more on safety. So we saw a handful of cases of uveitis and its in competitor trials. Could you just tell us tell me again about your broader clinical experience in terms of this kind of inflammatory signals even if miles are moderating on your view? And also, is there anything intrinsic to your design injector or the overall product profile that you believe mitigates these kind of events?

Sure, David, John, thank you very much for the question. With respect to intraocular inflammation, the studies usually divided into iritis, which is inflammation in the front of the eye and while somewhat troublesome or not typically site threatening, vitreous inflammation in the back of the eye, a little more serious in uveitis, which usually refers to inflammation in both those cavities. .

We do know historically, biologics can cause inflammation and there are various rates to the biologics. When they were first out their papers that were written that up to 10% or more of patients at certain times, we're getting at least mild inflammation. Obviously, inflammation is not ideal. And 1 of the real issues even in mild inflammation is the concern that it might actually be an infection, which can be much more serious.

So with respect to the 191 patients that we have treated in those 4 studies, we had 2 cases of its in both cases were mild, treated with topical drops and resolved quickly without any sequelae. We had no reported cases of uveitis, no reported cases of vitreitis. So the overall intraocular inflammation rate is just those 2 patients about 1%. We're optimistic and confident that drug shouldn't cause inflammation to a large degree because Varoli, of course, is a small molecule, it's not a biologic, we're not gene therapy. And the matrix that we're using, that 6% matrix in the inserts, that matrix has been used in our prior FTP products, and there was virtually no very low rates of inflammation recorded in those previous products.

So given that and given the safety profile, we've obviously seen in humans, which I just reported, the safety we've seen in animals, intraop inflammation is not something we're very concerned about.

Our next question comes from the line of Colleen Kusy with Baird.

Number of months still before the top line readouts of the wet AMD studies. But just a clarifying question on the reduction in treatment burden. The secondary endpoint. How do you plan on measuring that? Would that include the loading doses or is that measured after the loading doses. Just curious on the math there? And just what our expectations should be for reduction treatment burden. And then just an addendum to that, what would be clinically meaningful? .

Colleen, thanks for the question. First of all, the reduction in treatment burden is to be measured after load since all the patients in the WMB trials get loaded with 3 monthly injections. The treatment burden clock, so to speak, starts after that. So in the first year of the trial, the DURAVYU patients mandated should receive 2 DURAVYU injections. The EYLEA arm, the control arm has a mandated 5 injections. So if there's no supplementation in the entire study, we would expect a 60% reduction in treatment burden in the DURAVYU arm.

I can tell you that our expectations there will be some supplementation probably in both arms, just like there was in the DAVIO-2 trial, although we do believe it's likely that there will be less supplementation in the Phase III for various reasons. But if you apply the supplementation rates that we saw in Db2 to the Phase III we would have an approximate 40% reduction in treatment burden, which is excellent. So I think from the perspective of what the doctors want to see I think any kind of significant reduction in treatment burden will be welcome because a supplementation with a TKI in the real world is not a failure.

Doctors don't mind doing injections. They just want to do fewer number one. And obviously, the more important thing is they want to get better visual acuity for their patients in the long term. So the concept of sustained release is not about reduction in treatment burden. That's a positive side effect. But what we really want to see is better vision control in the long term, and we believe we can provide that.

I think some doctors may be excited about the possibility of using 2 MOAs having a ligand blocker biologic and having a receptor block at TKI at the same time. And that may prove to be better for long-term visual acuity results. So this whole idea of supplementation, it has a strict definition within the trials. But in the real world, I think the doctors will approach it a little bit differently. Now as part of the trial, I think, Ramiro, maybe can you comment on the superiority testing that we'll be doing about treatment burden?

Sure, Jay. So our our higher testing, none is going to be, as I mentioned before, the nonfronBCVA. The next 1 is going to be superiority on treatment burden. This study, of course, is well powered for the primary endpoint on CRTP CPA. For this key secondary endpoint in treatment burden, this study is also well powered and we should be able to detect the difference, even if the difference is 10% or 7%.

Our next question will come from the line of Lisa Walter with RBC.

Congrats on the progress. Maybe just 1 on safety. Wondering how we should think about the safety profile in Lugano Lucia as it relates to Davio-2. I believe in Dave to the 2-milligram arm performed better on things like iPay, cataract and floaters versus the 3-milligram arm. But my question is -- so how much of the safety or differences in DAVIO 2 are due to the 2 arms using a different number of inserts versus a different amount of drug? And how might this impact safety in Lugano, Lucia, where 2 inserts are being used like the 2-milligram arm in Daviot but the amount of drug is closer to the 3 milligrams that was used. Any color here would be helpful.

Sure, Lisa. First of all, with respect to dosage, we have animal data that shows no maximally tolerated dose of vorolanib so far. We dosed animals with approximately 10x higher dosing than we have ever done in a human. So we don't believe there will be any sign of vorolanib toxicity at the current doses that we're using even with reinjection. So no, I don't believe any of the AEs reported have been due to vorolanib. And I'd extend that to say so far, all the TKIs that have been used for wet AMD, as far as I know, there's no AEs that have been suggested to be due to the drug itself.

So these drugs at the doses we're using appear to be very safe in the back of the eye. With respect to insert number, the numbers are too low to really know, and that's not something we've really essentially considering. There was a higher incidence of floaters in VO2 with a 3-milligram 3 insert versus the 2-gram 2 insert. And maybe it had to do with a number of inserts but given that we're using 2 inserts in the Phase IIIs and ongoing, it's not much of a concern and especially because the rates were low, and we had nobody report decreased vision due to the inserts -- we had nobody leave the trials due to the inserts. Nobody has to have the inserts removed.

So from a clinical outcomes perspective we're really not concerned either about the number of inserts we're using or the doses of vorolanib that we're achieving. I think that the safety and the entire cohorts really speaks for itself.

And 1 moment for our next question. Our next question will come from the line of Yan with Laban.

And I recall in the press release, you have mentioned that there's a floater and the mechanism of actions of the drug could potentially reduce that. So could you elaborate a little bit more on that?

I'm sorry, you asked about the mechanism of action, reduce...

The drug, the drug that potentially could reduce floater or in of the .

No, I'm not sure I followed that. The mechanism of action of rolling it again includes its anti-VEGF effect. -- potentially the anti PDG effect to give a benefit to fibrosis and potentially the anti-IL-6 effect to give a better and quicker results in visual acuity. I don't think the MOA would have any effect on patients' perception of floater. And again, given that the rate of floaters for the whole 191 patients was 5.2%, and I just don't think it's a concern.

Okay. Yes, I just it says to prevent the free-floating drug particles...

That's the design of the inserts. And once again, the design of the insert, as we already stated, we designed these inserts so they control drug release until the drug is gone. That's the whole purpose of a sustained release insert is to control the drug release at therapeutic levels for an extended period of time. And so we would not expect for floating drug particles. We haven't seen free-floating drug particles in any of the animal studies -- and so far, there have been no reports of free-floating drug particles in the eye. So that is more of an effect of the delivery system, not the MOA of rolling it.

That's very helpful to clarify that. And then maybe a quick one. How many sites for the COO and the APRA study in total and the -- some of those are viewers U.S. versus in the U.S.

Ramiro, why don't you take that question, please? .

Yes. So we have -- both studies are global studies. So we have sites in the U.S. as well as outside of the U.S. We are planning to have approximately 140 sites across both studies. And we are leveraging a lot of the infrastructure that we use for our WebMD program. So a lot of the sites that are part of DME, most of them were also part of our wet AMD program, and which was very interesting and very encouraging for us is that all sites from the wet MD program that we invited to participate in the DME studies, they agreed to be part again of the DM program, which, again, I think highlights the confidence of the investigators in our clinical program.

Next question comes from the line of Daniil Gataulin with Chardan .

In your conversations with KOLs, what are you seeing in terms of which patients they would initially be willing to focus on when considering vorolanib, -- for example, the thinking more of stable patients versus newly diagnosed patients or patients with hybrid? And second part is, how do you expect the step through requirements to affect the adoption of vorolanib .

Thanks, Daniel. First of all, with respect to patient selection, I think we're all speculating a little here because we don't have the Phase III data in the label. But if 1 extrapolates from the Phase II data, I think that at the beginning, where most doctors will try it is there are patients who are being treated more frequently than they would like. every 4 weeks, every 6 weeks, every 8 weeks.

I think that will be the initial adoption of it. And as doctors get comfortable with its therapeutic profile and its safety, I think it will get expanded. Now I'll modify that a bit, which is if we can show in the clinical trials that we can deliver better vision than EYLEA on label or that we're antifibrotic or we have neuroprotection, other benefits that are potentially going to -- - that we might see, then I think the adoption will be much broader than that. I mean if we can show that we're antifibrotic, I think retinal physicians will acknowledge the fact that fibrosis in the long term is an important cause of visual loss, and if you can prevent it from happening, you will result in improved vision over the years.

So I think it will start off with the eyes that likely need a lot of treatment, but it may expand well beyond that. With respect to step therapy, we wouldn't anticipate it would be an issue. First of all, again, we don't know what our label will look like, of course, but our study in wet AMD is being done with a 3 injection load. So if the label contains use of review after 3 injections of an anti-VEGF, for example, then that automatically puts us beyond the initial injections into a branded drug.

I will say we are looking into the possibility of our different MOA and our 6-month efficacy, if it's there in the IL-6 blockage, if we can show a benefit there to be considered different than the ligand blockers, which may also be advantageous to us in the long term. But of course, that's all dependent on the data we show in the pivotal trials.

I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may now disconnect. Everyone, have a great day.

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Tessa Romero, and I'm one of the senior biotech analysts here at JPMorgan. Our next presenting company is EyePoint. And presenting on behalf of the company, we have President and CEO, Jay Duker. Jay, over to you.

Well, thanks, Tess, and good morning, everybody. I hope you've had your jolt of coffee this morning, but I expect this presentation and subsequent discussion will really wake you up. So as Tess said, I am President and CEO of EyePoint. These are our legal disclaimers, which if you'd like to read more, feel free to go to our website.

EyePoint is the leader in sustained-release drug delivery for retinal disease. And the #1 reason for that is our lead product DURAVYU. DURAVYU is currently in Phase III trials for wet age-related macular degeneration. Both trials are fully enrolled, and we anticipate the top line data from both trials this year, starting midyear. In addition, DURAVYU is also in Phase III DME and the program is underway, and we are on target to dose the first patients in both trials this quarter. Durasert is our proprietary delivery system, and it has been in 4 FDA-approved products with a strong safety and efficacy record. We have a veteran leadership team, some of whom are next to me up here in the podium. And we have over 3 decades of experience, not just with clinical drug development, but equally importantly, with the successful commercialization and manufacture of drug.

Speaking of commercial manufacturing, we built our own commercial manufacturing facility in Northbridge, Massachusetts. If you're looking for it on a map, it's right next to Uxbridge, Massachusetts, about 45 minutes west of our headquarters in Watertown, but obviously, that is still in the United States. That facility has been up and running for over a year. We now have about 60 employees there, and we are gearing up for pre-approval inspection as well as commercial success with manufacturer. Our financial situation is terrific. As of the end of the year, we had approximately $300 million in cash, which gives us a runway well past data into the end of 2027.

This is our pipeline. Again, we are in the 2 largest markets for retinal disease, wet AMD and DME in Phase III in both. In addition, we have a pipeline drug that is moving forward, EYP-2301, which is a TIE-2 agonist, also sustained release. Following the history of anti-VEGFs in both wet AMD and DME, it's an interesting story of how relatively small gains in durability led to very successful multibillion-dollar products. And in fact, the most recent, of course, is Vabysmo, now almost a $4.5 billion product 3 years after the launch with, again, just relatively minor improvements in durability. So here we are in 2026. And if you ask the question, okay, what are the unmet needs in these VEGF-mediated disease. The first one still is longevity because in the long term, despite these excellent drugs we have, patients still lose vision. And the primary reason for that is they just can't keep up with the necessary visits and injections over years. The second unmet need is new mechanisms of action. And it's becoming increasingly clear that VEGF suppression is not the only story, but inflammation plays an important role in both these diseases, and we believe DURAVYU will be the solution for both of these problems. Vorolanib, which is the active ingredient in DURAVYU, is a small molecule tyrosine kinase inhibitor with multi-MOA. It addresses both the vascular leakage that is the result of elevated VEGF and PDGF levels. And it does it, of course, with a new MOA at the receptor level. In addition, vorolanib is able to block IL-6 signaling also at the receptor level. IL-6 is a potent pro-inflammatory protein. And by blocking it, we can reduce not only inflammation leakage, but also suppress VEGF.

Our delivery system is called Durasert E. It's the next generation in sustained-release intravitreal drug delivery, and we have 3 decades of experience developing sustained release in the retina drug for drug delivery. Our technology, again, spans 4 FDA-approved products, including Vitrasert, Retisert, ILUVIEN and YUTIQ. DURAVYU is different in that it is fully bioerodible. The first iteration of DURAVYU had a payload of approximately 1 milligram of vorolanib, and our scientists were able to improve the insert so that the inserts now contain 1.34 milligrams of vorolanib. This represents a drug payload of 94% of the weight and volume of the insert.

Most intraocular inserts are about 50% to 60% drug. So this is a really unique formulation to deliver vorolanib sustained release. There are multiple advantages of DURAVYU. I've already spoken briefly about the multi-MOA, which we uniquely provide. But Durasert allows for immediate and sustained therapeutic levels of drug. In animals, we can measure vorolanib within hours after injection, and we can sustain it in humans for at least 6 months, and we believe virtually everybody. The release is also controlled, and this is important. We designed these inserts so the matrix holds the drug until the drug is completely eluded. So we control drug release until the end. Therefore, no free floating drug particles in the eye.

One of the unique aspect of this, which I think will really help us in commercial success is the convenience. DURAVYU can be shipped and stored at room temperature. All the other approved drugs, and I believe all the others that are in investigation now are either refrigerated or frozen. From a safety perspective, our inserts contain no PEG and contain no PLGA. I think this slide summarizes very well why we are so confident that DURAVYU will be a market leader. You can see the important things that retina specialists are looking for in treating these VEGF-mediated diseases. Of course, you have to have VEGF inhibition. But DURAVYU also has IL-6 inhibition.

In addition, we block PDGF, which should be helpful as fibrosis is another reason that eyes lose vision in the long term. We have at least 6-month durability, and we can redose, and we are testing it as every 6-month redosing. Also, ours obviously can be administered in the office through a standard intravitreal procedure. And as you look at the single approved sustained release device, that's the port delivery system and all the other competitors in the space that are being developed, we are uniquely positioned here. We've performed 4 trials and completed them successfully, including a Phase I called the DAVIO trial, which was previously treated wet AMD patients. And we are almost at the 5-year anniversary of the first patient dosed in that Phase I trial. And I do like to point out what great execution we've had over those 5 years. So we've gone in 5 years performing 1 Phase I, 3 Phase IIs, and we're now in 4 Phase III trials. The other Phase II were the DAVIO 2 trial, again, a large trial enrolling previously treated wet AMD patients, the PAVIA trial, which enrolled NPDR and the VERONA trial, which is our Phase II DME trial. All of these trials showed efficacy and all showed safety.

With regard to safety, as I'm sure you know, this is a really important topic in the retinal space. And I'm delighted that these 4 trials, there have been no reported ocular systemic SAEs due to the review of vorolanib, and we've had no safety signals. In addition, in the ongoing Phase III LUGANO and LUCIA trials for wet AMD, we're monitoring the masked safety, and we have seen similar safety as we have seen in these previous trials. Nothing new, nothing unremarkable. And I would like to add in the timing of the trials that all the patients who have enrolled in these Phase III, approximately 450 likely have received our drug. All of them have received the first dose. And by now, about 50% of them have got their second dose and the safety persists. So let's talk a little bit about the wet AMD program. We believe we're in the position to be first to market among all these investigational sustained delivery, and we believe we will have the best-in-class profile.

The key elements of the Phase III design is, first of all, we did a large Phase II, and we learned a lot from the Phase II about our drug, about how it works, about who it works in and how to conduct large wet AMD trials successfully. The trial was developed in align with both FDA and EMA. And in fact, we had European sites enrolled patients in the LUCIA trial. The primary endpoint is noninferior change in visual acuity versus an on-label Eylea control. This is the same trial design that the last 5 anti-VEGFs that have been approved successfully used. And we believe and have evidence, of course, that we will be the first pivotal program that's evaluating redosing of sustained release in both trials throughout the entire trial.

Both of these trials are fully enrolled, and they enrolled in record time. Each trial enrolled over 400 patients in about 7 months. Typically, wet AMD trials take about a year to enroll. And I think this is a testament, first of all, to how accepted our drug profile is in both the retina community and for patients. I think this speaks very well for our potential commercial success. The top line dates are a week 52, week 56 combined. And again, the first trial, the Lugano trial, we expect the top line data sometime in the middle of the year with LUCIA data to follow.

This slide shows the schematic of the pivotal trial design. Again, noninferiority regulatory pathway, which is the tried and true. We are testing a single dose of our drug, 2.7 milligrams of DURAVYU against the aflibercept 2-milligram control. And again, the FDA insists that if you're doing a non-inferiority trial, you have to use on-label either Lucentis or 2-milligram EYLEA, and you have to randomize the patients on day 1, and we're doing that. All patients get loaded with 2 milligrams EYLEA over the first 3 visits. And on the third visit, they either get a sham 30 minutes after the EYLEA or they get their dose of drug. Patients are then followed monthly. A masked observer determines whether or not the patient meets what we refer to as supplement criteria. So if the patients had recurrent fluid from best on study of 75 microns or drop in vision of 5 letters from best on study, then the eye will receive a supplemental EYLEA injection. Notice that we're redosing every 6 months. Primary endpoint is 52, 56 weeks combined, which is derisking and also at the request of the FDA, this is a 2-year trial. The second year is for safety. We will be able to submit the NDA after 1 year. This slide summarizes the results from our DAVIO 2 trial. It was both doses, 2 milligram and 3 milligram that were tested in the DAVIO 2 trial were statistically non-inferior to the EYLEA control. And you can see the absolute change in vision was less than 1 letter. Now remember, when you're reading the eye chart of the doctors, that line is 5 letters. So there was less than half a letter difference. And so statistically identical to on-label EYLEA.

All the other secondary endpoints were met, including a significant reduction in treatment burden between 75% and 90%, depending how you measure it. About 2/3 of the patients were able to go up to 6 months without reinjection. And we only injected these patients once with DURAVYU in this trial. And the trial went out to 12 months. 50% of the eyes did not need supplement injection at the end of the year. So while we are going for an every 6-month label, we believe some of the patients can go longer with this injection. The only difference, and you can see it on this chart is that the higher dose of 3 milligrams had slightly better anatomic control on OCT. OCT is a measure of permeability. Normal thickness in the retina is about 300 microns. When you get above 325 microns thick, that usually means there's excess fluid. So when you're looking at differences of 5 or 10 microns, that's less than the standard deviation on the test. The other thing I want to point out, and this is important, is while these were previously treated patients, both groups had an improvement in vision in this trial. So our drug was able to improve the vision, albeit slightly.

We went back and did multiple subgroup analyses from the DAVIO 2 trial. But one of the subgroup analyses that we did is we wanted to look at the patients who were in DAVIO 2 who would have been eligible for the pivotal trials. So some of the eligibility criteria was changed. And therefore, we wanted to see how the Phase III eligibility criteria would have affected the results from the Phase II. And the answer is it didn't. The results were robust for the patients who would have met Phase III criteria. You can see the visual acuities were between approximately 1.5 letters and 2 letters, and there was no statistical difference. The bottom graph is the OCT, which is the anatomic results of these same patients and notice again at the end of the study, very good anatomic control in all 3 arms. This gives us increasing confidence for the Phase III result.

About 1/3 of the patients were supplemented in the Phase II at the primary endpoint. However, we have changed the supplement criteria for Phase III. Ramiro Ribeiro, our CMO, who's at my left, his group did some important work to look at the supplements and answer the question, which supplements made a difference? In other words, if you had a supplement criteria, the patient received a supplement, but the vision didn't improve in a sense, you wasted a supplement and you didn't help the patient. So we then went back to DAVIO 2 and said, let's apply the supplement criteria that we're now using in pivotal to the DAVIO 2 patients. And say, how many would have been supplemented. So the bars on the left were the numbers of supplements from DAVIO 2 and on the right were the ones who met criteria for Phase III.

You may remember, and if not, I'll remind you that about 20% of the supplements in DAVIO 2 were at the physician discretion and met none of the criteria for supplementation. So you can see across all 3 arms, there would have been a significant reduction in the supplement rate by anywhere between 1/3 and 50%. And you can see in the higher dose, the 3-milligram dose, only about 13% of the eyes met the criteria, again, giving us confidence in the Phase III result. These pictures show you our new commercial facility in Northbridge, Massachusetts, 41,000 square feet, built completely from the ground up to our specifications by our landlord, and our landlord gave us a terrific deal. We didn't start paying rent until it was fully occupied less than a year ago. And so this facility was built to FDA and EMA standards, and we are currently completing registration batches for stability for our NDA. And again, we are amidst in preparing for not only the pre-approval inspection, but also for commercial success and the ability to scale and makes hundreds of thousands of inserts a year at the facility.

So now I'd like to talk about DME, diabetic macular edema, and we are the only TKI development at this point for DME and Phase III program underway. We had a very positive Phase II VERONA trial for patients with previously treated DME who are active. Again, this is aligned with both FDA and EMA. And we're using the same clinical trial infrastructure that we used for wet AMD, giving us confidence that we can enroll both of these trials rapidly. We are doing 2 trials in DME for global approval, but we are able to leverage the safety data from the wet AMD trial. So each of these trials will only have to enroll approximately 240 patients. This is the schematic of the Phase III DME program. We call the trials COMO and CAPRI. They're identical. And just small difference from the wet AMD trial is we're dosing DURAVYU on day 1, not at week 8. But again, it's non-inferiority change in visual acuity against EYLEA on label. EYLEA on label has a load of 5 injections monthly before it goes to every other month. We're only doing 3 injection load in the DURAVYU arm.

Secondary endpoints, of course, similar safety, resolution of fluid, percent of the eyes that are supplement free at the 1-year endpoint. This graph is from the high dose in the control group in the VERONA trial. All of these patients had active DME, they have fluid and decreased vision. On day 1, they either got an EYLEA injection or they got EYLEA and 30 minutes later, they got 2.7 milligrams of DURAVYU. The red boxes show you what happened at week 4. Notice the DURAVYU eyes at week 4 were already 4 to 5 letters better, and they were 50, 60 microns thinner. That to us did not represent solely a VEGF response, an anti-VEGF response. EYLEA is a great anti-VEGF. This represented something additional, and this is what set us out to discover that vorolanib was also a potent JAK1 inhibitor. And therefore, through that, we block IL-6. At the end of the trial, we were identical to EYLEA in this trial. And if we, of course, do a non-inferiority trial in the Phase III, so if we end up identical to EYLEA, obviously, we're going to be non-inferior and likely approved. But if we can show the same effect at week 4, we show better vision in dry retinas versus EYLEA. I think that will lead to great commercial adoption and success of our drug because what patient wouldn't want to see better faster. Now one of the patients in this high dose missed some visits. And you can see between week 20 and week 24, there was a drop in the vision overall from 10 letters to 7 letters. If you actually remove that patient, the rest of the group had a 10-letter improvement.

So we have increasing data, both preclinically and clinically that IL-6 makes a difference. I'm going to show you a study that Genentech did called the BARDENAS trial, which was a trial of diabetic macular edema patients who received either Lucentis on label or Vamikibart, which is an IL-6 biologic monthly. This is the improvement in vision if you give them Lucentis alone. When they received Vamikibart on top of the Lucentis, notice at week 4, there is a substantial improvement in vision over anti-VEGF alone, which was sustained.

On top of that, I've now shown you what happened with our 2.7 milligram eyes that were not supplemented, that they received an EYLEA on day 1, they received 2.7 milligrams DURAVYU on day 1, and they received nothing else for 6 months. And you can see it overlaps the IL-6 plus anti-VEGF blockage. What's the difference? We accomplished this in 2 injections. They required 12 injections to get that result. Some additional evidence from Verona. This is a measurement of vascular leakage, and that's a biomarker for vascular integrity. And you can see in a dose response, our drug reduced vascular leakage significantly more than EYLEA. And finally, a case, as you're probably aware, Vabysmo is really the treatment of choice for most doctors now in DME. This is a patient on the top right, you can see before the trial was getting Vabysmo monthly, suggesting that the retina specialists didn't feel that the response was enough to allow Vabysmo to be extended.

And in the top left OCT, you can see there's fluid. And by the time the patient got enrolled in the trial, the fluid had actually increased. They received 2.7 milligrams with one shot of EYLEA and received nothing else through week 24. And notice at week 24, this eye was 8 letters better than they were with Vabysmo and [ dryer ]. Now you can imagine if we can do this with a significant group of Vabysmo patients, how commercially successful we will be.

So in summary, only DURAVYU in the sustained release field shows a novel multi-MOA with 6-month durability. We have robust data from both Phase I and Phase II efficacy, both wet AMD and DME, favorable safety so far, including the mass safety data from our ongoing Phase III trials and the top line data is coming in approximately 7 months. The DME program will have first patient in shortly. Thank you very much.

Thanks so much, Jay. So I thought I would start our conversation here just taking a little bit of a step back and before we get into some of the details of DURAVYU and the emerging product profile, can you talk a little bit more about what you are seeing in terms of what physicians are reaching for in the market to try and extend the treatment interval for wet AMD?

Yes. So I think, again, with the data around the acceptance of Vabysmo shows it's now over a $4 billion product. High-dose EYLEA is approved as well, and I believe just recently got a label for every month dosing, and that's important to retina specialists. About 20% of eyes, no matter what you give them, have to be treated monthly. And if you look at the Vabysmo study, about 50% of the eyes could not be extended beyond 8 weeks. So despite these 2 innovative drugs, we still have a great need for more durable therapies. I suspect, and again, as a very, very part-time practicing retina specialists that these 2 will compete until a better sustained release option comes out.

And how has the feedback from the physicians and institutions evolved over time about DURAVYU? What is the level of awareness that you think is around the emerging TKI class in DURAVYU specifically?

Yes. So it's interesting because our commercial team talks about an A to B shift, meaning, A, is the way you do things now and B is the way we hope you do things in the future. And physicians are used to this paradigm of the next anti-VEGF saying, don't use the old one, use us because we are better, we last longer. We're not another anti-VEGF. We do things that they can't. We last 6 months and should be in virtually all patients. We block PDGF, we block IL-6. So we have other things to offer their patients. And in addition, it's not an either/or. I notice in our patient -- in our studies, all the patients are getting loaded with EYLEA and some get supplemented with EYLEA. So the idea of using 2 mechanism of action, I mean, what chronic disease nowadays isn't treated with more than one mechanism of action, including glaucoma. Our ophthalmologists are used to that. And I think that will be likely a paradigm that's going to be used.

Okay. And just a couple of housekeeping questions before we get into some scenarios around the data. Should we expect 2 top line announcements from EyePoint or do you think they're going to be together?

So the plan right now is they're likely to be separate. One never knows, but our plan is to when we have locked the data on the first trial and are confident in the result, we will release it.

Okay. And if I did my math right, maybe I didn't, but it seems like there will be one more DSMC meeting before the top lines.

Ramiro, do you want to comment on that?

Yes.

And maybe what you've seen to date might be helpful, too.

That's right. So we, as a company, we provide oversight of the safety of the studies on an ongoing basis. So we review that data on a masked fashion, of course, on an ongoing basis. And then we have an independent DMC that reviews the masked data every 6 months. So we had so far 2 meetings, the last one in November. We're going to have another one in May. So this is before the top line results. They're going to be reviewing the data. So far, both the mask assessment tell us that the safety profile overall is very similar to what we have seen before in our Phase I, Phase II studies. So everything as we expected. And very importantly, the DMC reviewed the mask data and told us that there is no need to change the protocol or the conduct of the study.

Okay. And what -- can we talk a little bit more about what you think represents positive data here for each of these studies? And what relevant detail do you plan to provide at the time of your top line?

Sure. So I think...

Sorry. And Jay, just in that context, just I know we talked a little bit about your primary endpoint, but what are you specifically looking for around your secondary endpoints of reduction in treatment burden and percentage of eyes free of supplemental EYLEA injections?

So I do believe it's going to be pretty straightforward. We need to be statistically noninferior to 2 milligram EYLEA. The actual numerical difference will probably not matter unless we're superior. And frankly, while that's not our expectation of superiority, we have some data to suggest that we could be numerically superior, including the DME data without that outlier, we were 3 letters better.

And the wet AMD data, if you looked at our DAVIO 2 trial and you just looked at the unsupplemented eyes, the DURAVYU arms did slightly better visually than the EYLEA did. But we need to be obviously to hit the primary endpoint. And I do like to remind everybody that retina specialists, if we're a letter or so worse, probably doesn't matter. High-dose EYLEA was 1.4 letters worse than 2-milligram EYLEA, but it hasn't stopped my colleagues from using the drug. Obviously, safety that goes hand-in-hand with efficacy here. And you just heard from Ramiro that we now have given our drug to approximately 650 patients and really aren't seeing anything at this point, which would suggest an issue. Obviously, the study is not done yet there.

And the third thing we need to do is in the secondary endpoint is be statistically superior to 2-milligram EYLEA in reduction in treatment burden. And I have to say when you actually do the stats on that, that should be an easy bar to hit. The percentage of eyes that are rescue-free, I think, will help us from a commercial perspective, but not sure it's actually as relevant to the FDA. Just like the OCT data, important to retina specialists, but probably not as relevant to regulatory. So again, there's 3 things we need to hit. I like to hit them in both trials. Both trials are essentially identical. And so we have quite a bit of confidence based on the data that I've talked about already today that we will be able to achieve that.

Okay. So in that context, what keeps you guys up at night?

Did the time change? No. I have to say, I've been in this role about 2.5 years, and I've learned a lot in a very short period of time. And one of the things I've learned is we have a really, really good team of people. And for those of you who do drug development, you know every day is a new challenge. But when you see how your team fights through the challenges, some easy and some hard, you get very confident in their ability to tackle anything. And I do want to point out, again, Ramiro's clinical team, we did faster and I hope better recruitment to those Phase III trials than all of the big companies, Roche Genentech, Regeneron, we did better.

So what keeps you awake at night is we have a daunting task. I think we have a great drug that has a lot of advantages over the ligand blockers, but we're going to have two 10,000 pound gorillas out there, Roche Genentech and Regeneron that we'll be going up against. But we have enough differentiation that if approved, I think we will carve out a very, very good market share.

Okay. And assuming positive data here, how quickly do you think you can file in the U.S. and Europe?

Ramiro, do you want to take that one?

Yes. So I think the same efficient work that we have done with the enrollment, we're going to be looking to do that for the database lock as well as the submission. The beauty of our program is that the 2 studies are identical, and we're going to get Lugano first. So we're going to get that data. We're going to start to write the CSR, the modules. And then we get the LUCIA data which, again, because this says are very similar, the write-up of those documents should be quite quick. If you look at industry standard, submission is about 6 months after a database lock. We believe we can do better than that for the U.S. and then after that for EMA.

Okay. Great. And how are you thinking -- I think there were some comments in your presentation here, but just to maybe elaborate a little bit more. How are you thinking about the TAM for wet AMD? And what is the reasonable penetration of the market for an extended-release TKI like DURAVYU? And what -- are there any potential challenges that you envision from an adoption standpoint?

So let me take the last one first. From an adoption perspective, again, doctors are used to doing things in a certain way. And so one nice thing about being in retina is we're at heart surgeons. And so we don't always follow labels or directions all that well. And we're not afraid to try new things. So I think that's going to help with our adoption. And when you talk to some of the younger retina specialists, they are just overwhelmed with injections, and they really want the ability to take at least some of their patients out longer so that they can actually not be working until 8 o'clock at night seeing 100 patients in the day. I'm sorry, I took the last one first. So could you -- what were the other 2 you asked?

I don't know. Is it only Tuesday? No. Just talking through any challenges and just how you think about TAM, but you kind of covered it, I think.

Yes. The challenges, again, are really educational is to educate the physicians on quite simply who to use the drug in and how to integrate it into your practice. And the whole concept of it's not an either/or. You don't have to give up your favorite anti-VEGF. And if you want to use 2 MOAs, feel free. We can dose products that are approved once every 28 days. And so alternating a ligand blocker with a sustained-release TKI can make sense.

And I just wanted to ask kind of a quick question here. Just we know there's a competitor out there that has a study reading out shortly, the Phase III [ SOL-1 ] study. Can you maybe talk through, Jay, really what I'm interested in is what the read-throughs are for your program from those data from your perspective?

So sure. So at a high level, I think we already know this. TKIs work. There's been, to my knowledge now, 8 TKI trials with various delivery systems, intravitreal, orally suprachoroidal and wet AMD, and they've all been positive. And so I do expect the study to show a positive benefit of TKIs. Beyond that, however, the study design, again, is very, very different than what we're doing. And given that retinal physicians don't typically watch patients lose 15 letters, it's hard to know how applicable that result will be in the real world. But again, I go back to our trial design. We're going up against 2-milligram EYLEA on label. I believe physicians, if we're positive and approved, they will know exactly how to use us because they know what other products do against 2-milligram EYLEA because that's been the standard.

So maybe a couple of quick hits to round us out here. Just turning now to DME. How derisked do you think your Phase III trials are here? Like any nuances to be thinking about from like an opportunities and challenges point of view?

So I think we're very derisked in DME. Again, we had a very good result in the Phase II, and we block IL-6. And if you look at some of the data on that, for example, there's a study that was done where they were doing vitrectomy on eyes in the eyes that had diabetic macular edema had significantly higher IL-6 levels than normals or diabetics without diabetic macular edema. We know that high IL-6 levels result in poor response to anti-VEGF. And again, we showed you some of the combo data for anti-VEGF and anti-IL-6. So we believe that's going to be a significant advantage not only in the trial, but in the real world. Once again, who wouldn't like to see better faster with less injections. So I think the DME results, I'm very confident in them given the positioning and given the study design, I -- we are quite confident in the results.

Last question for me to round out the conversation here is maybe you could just remind us of your cash on hand and what milestones that allows you to complete to bring you in, George?

Go ahead, George.

Yes. So as part of the presentation, we ended 2025 with just over $300 million of cash, puts us our cash guidance remains unchanged into Q4 '27 that funds all of the ongoing Phase IIIs, including the 2 DME trials, which we expect to read out sometime in Q4 of '27. And so when we read out the wet AMD trials later this year, we'll have well over a year of cash. So we're feeling great about our balance sheet, no debt.

Okay. And any considerations just around commercial supply build-out?

Yes. So that's included in our projections as well. As Jay pointed out, our Northbridge facility is up and running. We've had remarkable activity there, and we're gearing up to meet that CMC section and registration batches, and that will also continue to support some of the initial commercial build.

Great. Thank you so much to the entire EyePoint team for being here, and appreciate all the listeners for joining as well. Thank you.

Good morning. My name is Antoine, and I will be your conference operator today. At this time, I would like to welcome everyone to the EyePoint Third Quarter 2025 Financial Results and Recent Corporate Developments Conference Call.

Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to George Elston, Executive Vice President and Chief Financial Officer of EyePoint. Please go ahead.

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's third quarter 2025 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer of EyePoint.

Jay will begin with a review of recent corporate updates and discuss our clinical programs for DURAVYU in wet AMD and DME. I will close with commentary on the third quarter 2025 financial results. We will then open the call for your questions where we will be joined by Dr. Ramiro Ribeiro, our Chief Medical Officer.

Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of this release can be found in the Investor Relations tab on the company website, www.eyepointpharma.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, financial projections and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we have made or may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.

Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of EyePoint.

Thank you, George. Good morning, everyone, and thank you for joining us. I am pleased to discuss with you today the tremendous progress we've made during the past quarter, continuing our strong track record of execution. As you will hear, our momentum underscores our confidence in the differentiated clinical profile of DURAVYU, our lead program and its potential to transform the treatment paradigm in the 2 largest retinal disease markets, wet Age-related Macular Degeneration or wet AMD and Diabetic Macular Edema, or DME.

I'd like to start with a brief overview of our recent highlights. DURAVYU is on track to be the first to file and first to market among all current investigational sustained delivery wet AMD and DME programs, positioning DURAVYU at the forefront of the treatment landscape with potential first-mover advantage. We completed enrollment of the LUCIA trial, the second Phase III trial for DURAVYU in wet AMD in July. Both trials, LUGANO and LUCIA were enrolled in 7 months and together recruited over 900 patients, making them among the fastest enrolling wet AMD pivotal programs to date.

Top line data for DURAVYU and wet AMD is expected in mid-2026. Following the positive end of Phase II meeting in July for DME, we were pleased to align with the FDA on a non-inferiority trial design that we believe is clinically rigorous, efficient and derisked. As a reminder, DURAVYU is the only tyrosine kinase inhibitor or TKI in development for DME. We are rapidly moving forward with a pivotal Phase III DME program with first patient dosing expected in Q1 2026.

The Phase III DME trials, COMO and CAPRI will leverage our existing wet AMD clinical trial infrastructure and our enthusiastic network of investigators.

We announced new preclinical data showing that vorolanib, the active drug in DURAVYU, is unique among TKIs being tested in retinal diseases as it inhibits both [ VEGF ]-mediated vascular permeability and interleukin-6 or IL-6 mediated inflammation. This multi-mechanism of action has the potential to be particularly effective in the treatment of multifactorial diseases such as wet AMD and DME. These new data underscore the impressive Phase II results of the VERONA trial in DME and strengthened our confidence in our clinical programs.

Finally, our path to potential success in Phase III is supported by our strong balance sheet. We ended September 2025 with over $200 million in cash and equivalents and closed a $172 million follow-on offering in October. Our cash is now expected to fund operations into Q4 2027, well beyond Phase III wet AMD data anticipated in 2026. With this continued exceptional track record, EyePoint will enter an eventful 2026 from a position of strength.

Now I'd like to take a closer look at the current market landscape for wet AMD and DME. With a combined current global market of $10 billion and growing, these indications make up the vast majority of the global branded retinal disease market. Despite the size and scale of these diseases, they are dominated by a single treatment modality, monotherapy anti-VEGF biologics. Due to the high burden of frequent injections, many patients remain undertreated, even with the addition of recently approved extended duration options.

Additionally, these current standard of care anti-VEGFs demonstrate subpar real-world efficacy in DME with growing literature supporting the role of not only VEGF activation, but also IL-6 signaling and inflammation driving disease severity. We believe our lead product candidate, DURAVYU, is well positioned to deliver much needed innovation in both wet AMD and DME. As a differentiated sustained-release TKI, DURAVYU is designed to improve the current standard of care by providing durable disease control while reducing the treatment burden.

Further, DURAVYU's potential multi-MOA blocking VEGF, PDGF and IL-6 signaling may be uniquely suited to effectively address multifactorial retinal diseases such as DME and wet AMD. Beyond its unique MOA, DURAVYU offers a compelling product profile that supports strong competitive positioning in both wet AMD and DME. Unlike other sustained release options in development, DURAVYU is formulated in our Durasert E technology. a biodegradable sustained release insert specifically designed to prevent free floating drug particles.

Additionally, DURAVYU is shipped and stored at ambient temperature and administered via a standard intravitreal injection. DURAVYU features the most robust clinical data package among all investigational sustained release programs. This includes Phase II wet AMD and DME data, demonstrating meaningful visual and anatomic improvements from a single DURAVYU dose and a consistent and favorable safety and tolerability profile with no safety signals observed in over 190 patients across 4 completed clinical trials.

Given its advantageous clinical profile, multi-target MOA and unique storage and administration conveniences, we are confident that DURAVYU offers a differentiated value proposition that is meaningful to physicians and patients. And if approved, would present a compelling option within the current and future landscape for retinal disease treatment. Let me now walk through recent updates for our Phase III programs, beginning with wet AMD.

Our fully enrolled Phase III pivotal program remains on track to deliver top line data starting in mid-2026. As a reminder, in July, we completed enrollment of the Phase III program with over 900 patients randomized across the 2 trials. To ensure we are positioned for commercialization, we are highly focused on our manufacturing capability and CMC submission for an [ NBA ]. We have already produced DURAVYU registration batches at our state-of-the-art GMP-compliant manufacturing facility in Northbridge, Massachusetts. The 41,000 square foot facility was built to both U.S. FDA and EMA standards and will have capacity to support the commercial launch.

Moving on to the recently initiated Phase III program in DME. Our program consists of 2 non-inferiority trials, COMO and CAPRI, evaluating DURAVYU 2.7 milligrams versus on-label aflibercept control. Each trial will enroll approximately 240 patients. Additionally, given the established non-inferiority pathway as well as our ability to leverage our existing Phase III clinical trial infrastructure, we believe the program is significantly derisked. We look forward to dosing our first patient in Q1 2026.

As I mentioned earlier, there is growing clinical evidence supporting the multifactorial nature of retinal vascular diseases with both VEGF-mediated vascular leakage and inflammation contributing to disease pathogenesis. IL-6, a pro-inflammatory cytokine is a key driver of this inflammation and is found at significantly higher levels in DME and wet AMD patients versus healthy individuals. Recent preclinical findings, which we presented at the American Academy of Ophthalmology meeting in October, demonstrate that vorolanib, the active ingredient in DURAVYU, inhibits IL-6 signaling through [ JAK1 ] receptor blockage in addition to its known inhibition of PDGF and all VEGF receptors.

In vitro data shows a meaningful reduction in IL-6 activity of more than 50% with vorolanib, suggesting a multi-MOA capability. This data may explain the rapid fluid reduction and vision improvements observed as early as week 4 in the DURAVYU arms in the Phase II VERONA trial.

In summary, we are well positioned to extend our clinical leadership in sustained release therapy for the 2 largest retinal disease markets. We remain focused on reporting top line Phase III data for both LUGANO and LUCIA starting mid next year, positioning DURAVYU to be the first to file and potentially first to market among all investigational sustained release programs in wet AMD.

Our Phase III DME program is now underway, and we expect first patient dosed during the first quarter of 2026. We are moving swiftly and confidently to bring DURAVYU to patients in need while continuing to ensure our progress follows a derisked, clinically rigorous and patient-centric approach. Before passing it over to George to review our financials, I want to thank the entire EyePoint team for your dedication to improving patients' lives through better vision as well as the patients, study coordinators and clinical investigators outside of our organization who enable our clinical research. We are grateful for your confidence, and we are proud to advance our therapeutics for the benefit of the entire retina community. We look forward to continued progress towards our upcoming milestones as we further our leadership in sustained ocular drug delivery. I will now turn the call over to George. George?

Thank you, Jay. To begin, we continue disciplined financial management and good stewardship of our resources, ending the third quarter with $204 million in cash and investments. As Jay mentioned, in October, we completed a $150 million follow-on financing plus the exercise of the underwriter's greenshoe option on October 29 for a total of approximately $172 million in gross proceeds, adding to our cash position and enabling the execution of the Phase III DME program.

We expect that cash and investments as of September 30, along with net proceeds of the financing will support our operations into the fourth quarter of 2027, well beyond key data readouts from the Phase III LUGANO and LUCIA pivotal trials anticipated in mid-2026. As the results for the 3 months ended September 30, 2025, were included in the press release issued this morning, my comments today will be focused on a high-level review for the quarter.

For the quarter ended September 30, 2025, total net revenue was $1 million compared to $10.5 million for the quarter ended September 30, 2024. This decrease was primarily driven by the recognition of deferred revenue related to the company's 2023 agreement for the license of YUTIQ product rights in the prior year period. Operating expenses for the quarter ended September 30, 2025, totaled $63 million compared to $43.3 million in the prior year period. This increase was primarily driven by clinical trial costs related to the ongoing Phase III LUGANO and LUCIA clinical trials of DURAVYU for wet AMD.

Net nonoperating income totaled $2.3 million and net loss was $59.7 million or $0.85 per share compared to a total net loss of $29.4 million or $0.54 per share in the prior year period. As I noted earlier, cash and investments on September 30, 2025, totaled $204 million compared to $371 million as of December 31, 2024, which, along with net proceeds from the October financing, we expect will enable operations into Q4 2027.

In conclusion, we are very pleased with our progress and continued execution in 2025 and are well capitalized to deliver DURAVYU Phase III wet AMD data in 2026, while advancing our Phase III DME program with the COMO and CAPRI clinical trials. I will now turn the call back over to Jay for closing remarks.

Thank you, George. As you've heard this morning, EyePoint is on the cusp of a milestone year in 2026. Our decades of drug development experience, clinical track record, next-generation technology and blockbuster potential of our DURAVYU franchise underscore our exciting growth story. With our strong balance sheet and disciplined cash management, along with our thoughtful derisked development strategy, we are prepared to execute through our key upcoming milestones, including top line data for the Phase III LUGANO trial anticipated in mid-2026 with LUCIA data to closely follow, positioning us for a potential MDA submission for DURAVYU in wet AMD and the first patient dosing in our pivotal Phase III DME program anticipated in Q1 2026, with full enrollment expected in the second half of 2026. Thank you all for your attention this morning. I will now turn the call over to the operator for your questions.

[Operator Instructions] Our first question comes from Tess Romero from JPMorgan.

I wanted to ask a market sizing question today. Can you just refresh us for the wet AMD population overall here in the U.S.? What percent of patients are treated every 4 weeks, every 6 weeks, every 8 weeks or longer? And what is your latest view on how the doctors will use DURAVYU, if available in that context?

Thanks for the question. It is insightful. And as you may surmise, the data is not strong to give exact numbers for each of those intervals. What we do know is approximately 20% of wet AMD patients have to be treated monthly regardless of the drug that they're using. If you look at the clinical trial data, even with the newer extended duration agents, 50% of the eyes can't go longer than every 8 weeks. Depending on a doctor's toleration for fluid, some patients can certainly go 3 and 4 months in between injections. But again, it's individualized to the patient and oftentimes individualized to the doctor's tolerance of fluid and adherence to the label.

So I don't, off the top of my head, have exact numbers to give you for those other percentages. And I'll pause and see if Ramiro has any other insight.

Yes. No, thanks, [ Tessa ], for the question. I think when we think about DURAVYU, in our Phase II data, we showed that after dosing DURAVYU, about 65% of patients did not require any supplemental injection with anti-VEGF. And even when we look at 0 or 1 injection over that 6-month period, then the number is about 90%. So we believe that DURAVYU is really well positioned if we see the results in the Phase III study being replicated to bring the market for wet AMD patients.

And to answer the second part of your question, Tess, I don't think you can look at it as an either/or, meaning if DURAVYU is approved, doctors will be limited to just using one agent. We're a different MOA. And clearly, the more recent data with IL-6 inhibition suggests that we may offer an MOA that the [ ligand ] blockers cannot. That would open up market tremendously to us. And as Ramiro just explained, physicians, I'm sure, would be willing to take advantage of 2 MOAs. We do that in chronic diseases all the time. And therefore, the market share for DURAVYU, when you speak to some of the KOLs on the podium even recently have said up to 80% of their patients would be eligible. So we're really optimistic that the acceptance of a multi-MOA TKI with sustained release in both wet AMD and DME is going to be high.

Our next question comes from Yigal Nochomovitz from Citi.

This is [ Jen Kim ] on for Yigal. Regarding DME, can you provide any additional color on how you're structuring your enrollment criteria to provide the broadest reach in the DME marketplace relative to competitors in the long-acting TKI space?

Sure. I'll let Ramiro answer that question. Thank you very much for it. And again, I can quickly answer the second part of the question. We're the only TKI sustained release that has a DME program. So that part is easy. But Ramiro, why don't you talk a little bit about how we've designed the trial?

Yes. So first, to give an overview on our Phase III DME program, CAPRI. So we are going to be enrolling patients with active DME, both treatment naive and previously treated. as a control arm, we're going to use aflibercept on label and then DURAVYU is going to be being dosed every 6 months. We are very fortunate to have a strong infrastructure here at EyePoint as we conducted our wet AMD study. We have also a very strong relationship with investigators. So for our DME program, we're going to be able to leverage those strengths into a hopefully rapid enrollment for the DME program. I think it's our understanding that we might be the only Phase III program enrolling patients next year for this indication. So again, I think we expect to see a rapid enrollment, similar strength that we did for the [ wet AMD ] program.

And regarding enrollment, just for clarification, I believe I heard you say second half ' 26. Is that for both COMO and CAPRI?

So I think what we're guiding now is that both studies are going to be starting Q1 of next year, 2026.

Our next question comes from Tyler Van Buren from TD Cowen.

This is Sam on for Tyler. I wanted to ask about the use of the blended endpoint, which you guys have remained consistent on with the pivotal wet AMD and DME trials. We have seen the FDA greenlight a single endpoint more recently. So curious if you thought about using a single endpoint at all for the DME studies and why you believe the blended endpoint is the best approach?

Thanks, Sam. I appreciate the question. And I'll let Ramiro go into the details. But to answer quite simply, did you think about a single endpoint, quick answer is no. Ramiro, why don't you talk a little bit about our interactions with the FDA over endpoint and why the blended endpoint is actually derisking?

Yes. Thanks, Sam, for the question. So for both our wet AMD program and our DME program, we are using blended endpoint, meaning that for the primary endpoint, we're counting 2 visits. The benefit of that is that we prevent missing data. So in this type of study, it is not uncommon to see patients missing the visit because they have medical appointments or they're in the hospital for some [ systemic ] disease. So by having 2 visits, we reduce the amount of missing data. And also very important, if a patient has, for any reason, a loss in vision in one of the visits, they have the ability to capture the recovery of that vision in the next visit.

The use of blended endpoint has been common in clinical trials for retinal disease for the past few years with the main goal of decreasing the variability and increasing the power of the study. And that's why we feel confident on using the blended endpoint for both wet AMD and DME. And of course, we have the green light from the FDA to do so.

Our next question comes from Claire Dong from Jefferies.

This is Jenna on for Clara. Could you talk about the differentiation in IL-6 inhibition? And could you help us kind of elaborate on how that could translate into clinical benefit in DME versus an anti-VEGF only approach?

Thanks for the question, Jenna. And this is really timely because you may be aware, there's some recent data from Genentech who used an IL-6 blocker in a DME trial combined with an anti-VEGF. Both were delivered monthly and the arm with the IL-6 blocker along with the anti-VEGF had better vision as early as week 4 and sustained through the trial. We were able to show a very similar vision improvement and course of improvement in our VERONA trial using just 2 injections over 6 months as opposed to 12 injections over 6 months. And when we looked into it more closely, we discovered that, in fact, vorolanib is a potent inhibitor of IL-6 pathway by blocking the JAK1 receptor.

There is substantial evidence in both wet AMD and DME that IL-6 plays a pathogenic role, especially in eyes that are not responding. And therefore, the ability to block both VEGF pathway and inflammatory IL-6 pathway could be a significant improvement over what we have now, especially coupled with sustained release. so that you're not having to give 2 biologics on a monthly basis.

Our next question comes from Yatin Suneja from Guggenheim.

Maybe 2 questions from me. One is on the mechanism regarding the IL-6. Jay, if you can comment on the relevance of it in one disease versus the other? Do you think there is more relevance in DME versus AMD? So that's one. And then the second question is now more around the expectation now that the studies -- wet AMD expectations, right. Now the studies are enrolled, I think our investors are sort of beginning to think about what we should be expecting from the data. And I think there is focus on 3 things. One is the BCV and noninferiority, what sort of injection burden you can produce? And how should we think about rescue rate? So if you can comment on that, that would be very helpful.

Thanks, Yatin. Two great questions. Let me start with the IL-6 question. IL-6 has been implicated in inflammatory macular edema for well over a decade. And additional data suggests that IL-6 levels in the vitreous are much higher in DME patients than in diabetics with no diabetic retinopathy. In addition, there's data that suggests high IL-6 levels in aqueous humor portend a worse outcome in both DME and wet AMD.

So overall, the evidence for a role of IL-6 as an inflammatory pathway in DME is very strong. And while it's there in wet AMD as well, it appears to be a prognostic factor in the percentage of eyes that aren't doing well with VEGF blockage alone. We believe that if the preclinical data we have shown and the rapid and early and sustained response in our VERONA DME trial can be shown in Phase III. This would be an exceptional result, which would put us at the forefront of both wet AMD and DME therapies.

As for the clinical trial results, which we expect, again, the first trial, LUGANO mid next year, second trial LUCIA soon to follow. Based on our strong Phase II data, we would expect non-inferiority to the on-label Eylea control with continued safety. And again, safety is of paramount importance here, as I'm sure you all know. But based on the ongoing mask safety that we've seen in these 2 Phase III trials as well as the extensive safety database we have for both DURAVYU and vorolanib.

we're confident that the safety will be quite good. As for reduction in treatment burden, again, that's important. There's no specific cutoff that says it has to be above or below a certain level. And based on our discussions with KOLs and the design of the trials, we think a 50% reduction in treatment burden will, again, put us into the forefront of therapies for wet AMD.

Our next question comes from Debanjana Chatterjee from Jones.

Congrats on all the progress. So assuming LUGANO and LUCIA meets its, the non-inferiority endpoint, does your statistical analysis plan allow for testing superiority? And if so, how do you expect clinicians to interpret those data related to on-label Eylea compared to potential competitors pursuing superiority claims based on like less frequent dosing?

So Ramiro, why don't you answer that? Thanks, Debanjana. I appreciate the question.

Yes. Thanks for the great question. So our -- as you mentioned, our analysis plan does allow for testing superiority again, aflibercept if our noninferiority is met. So it's a hierarchical testing. So we have the ability to test for that. Of course, if we see that DURAVYU produce superior visual outcomes compared to on-label aflibercept, then, of course, I think it will be an outstanding results for the retina community and wet AMD patients and would allow us to position DURAVYU as a premium medication. Of course, having a superiority claim against on-label aflibercept, I think from a retina specialty perspective is much more relevant than having a superiority versus a single dose of aflibercept.

So we are -- we continue to be optimistic with our LUGANO and LUCIA study. We were very fortunate to have the [ DABE2 ], our Phase II study to support the design of the Phase III programs, a lot of the learnings coming from there, and we're looking forward to see the results mid next year.

This concludes the question-and-answer session. I will now turn it over to Jay Duker for closing remarks.

Thanks very much. Before we close, I do want to mention a tremendous honor that EyePoint received this week. We were voted a 2026 Best Places to Work by BioSpace. In fact, we were in the top 5 best biotech companies nationally. This is a testament to the incredible team and culture we built here at EyePoint. Exceptional execution does not come in a vacuum.

I want to thank all of our amazing team for this honor, but especially our human resources group led by our Chief People Officer, Jen Leonard. Thank you all for your time and attention this morning.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

[Audio Gap]

With EyePoint. [Operator Instructions] and welcome as well to those listening on the webcast. I'm Yigal Nochomovitz, biotech analyst here at Citi. So I have the pleasure to introduce senior management from EyePoint Pharmaceuticals, Jay Duker, CEO; George Elston, CFO. Welcome, both of you. Thank you very much for making the time to chat.

So obviously, a very busy time for the company. and for the wet AMD space. So I think just to start out, why don't you -- Jay, if you could spend just a few minutes just introducing the company, the therapy you're advancing, the key trials, obviously, in Phase III trials in wet AMD, and then we can get into a lot more detail from there.

Sure. Thank you, and thanks, everybody, for coming. EyePoint does drug delivery to the back of the eye. We've had 4 FDA-approved products with our technology. The latest technology is a fully bioerodible insert that contains vorolanib, which is a small molecule tyrosine kinase inhibitor that has activity against all the VEGF receptors.

We're in Phase III in 2 trials for wet age-related macular degeneration, which is the largest market of all the retinal vascular diseases, about $10 billion a year in the United States alone. We recently announced that we are fully enrolled in both of those trials. They are identical trials, which primary endpoint is noninferiority change in visual acuity against on-label aflibercept control.

So we are very excited generally where we are right now. As I said to many people, if we had mapped it out 4 years ago, when I first joined the company full time that this is where we would be. At this point, I would have said very low probability success. But here we are, and that's because we really had a great, great group of -- who are able to execute on all these milestones that we've achieved, including this enrollment for these 2 trials.

Each of the trials enrolled in approximately 7 months, which are the fastest enrolling wet AMD trials on record. One of the reasons, of course, is that we had really good Phase II data in wet AMD, which was helpful for the sites to convince patients that this is a trial that they might want to enroll in. And of course, it also, I think, speaks very well for our potential commercial success and that a sustained release insert that releases drug therapeutically for 6 months or longer with a single injection is something that's very attractive to both patients and practitioners.

Well, I was going to ask what you attribute to the speed of enrollment. You sort of sort of got to that already.

I did. Sorry, I should have paused [indiscernible] your question.

No problem.

There are other reasons though and our Chief Medical Officer, Ramiro Ribeiro, who's here, I need to give him and his team full credit here. Ramiro's experience, he's run Phase III retina trials internationally before his experience and his ability to lead a team, I think, has been very helpful in our success. But the fact that we did run a Phase II trial and we learned a lot of lessons from the Phase II, not just got great results, top line and safety.

But we learned about how our drug works. We learned about the statistics of the trial. And I have to say, at the beginning, especially, we made a few mistakes, and we learned from the mistakes. And towards the end of the enrollment in the Phase II, we were enrolling very rapidly. And we took those lessons and applied them to the Phase III.

Our Phase III program, again, we took a derisked view of this, meaning we did a noninferiority type trial design, which is how the last 4 approvals in wet AMD were structured. And we were able to really connect with the retina community based on our data and based on our personnel and based on what we call the patient-centric focus of the trials.

Everybody in the trial gets treated. We have rescue criteria or supplemental injection criteria, which means if a patient was losing vision in either arm, either the treatment arm or the EYLEA arm, they could get a supplement injection to help ensure that they don't lose vision in the long term. These are the type of things that doctors and patients are very appreciative of.

Speaking of the rescue criteria, just if you could go into a little bit more detail on how those rescue criteria sync up with how one would behave with a patient in a real-world setting and how closely that aligns.

So let me start by saying that the idea of a rescue criteria, supplement criteria is relatively new. The sustained release treatments, all of them, which started to be studied several years ago in the Phase I contained supplement or rescue criteria, meaning if a patient wasn't doing well by some measure, they could receive an extra injection.

The problem, as you point out, Yigal, indirectly there is, if you say, how does that correspond to the real world? It doesn't. None of us, and I am still a practicing retina specialist, none of us use strict criteria in deciding whether to either give a patient an extra injection or shorten the interval between injections. And the reason is we individualize therapy. And we have a patient sitting in front of us depending on whether their vision is good or bad, whether the other eye is involved, whether they perceive a problem or not, there are social issues around intervals. Some patients just cannot get treated every month and if they need it.

So that idea of a supplemental injection or rescue injection is not something we use in the real world. But it is something that you need to ascribe in order to get these trials done and have them given the FDA sign off. Interestingly, if you look at these trials, you'll realize that the supplement criteria is different with different trials and with different companies. That is because at this point, the FDA acknowledges that there's not a standard out there and allows sponsors to determine their rescue criteria. So a little more detail around that.

In the Phase II, we had a lot of different rescue criteria, and Ramiro and his team took a look at the Phase II data and asked the question, which of the rescues actually made a difference and improved the visual acuity? And it came down to just one, 5-letter loss from BESTON study associated with 75 microns of new fluid on OCT. That was the single important rescue criteria we came out with for the Phase III.

In addition, in the Phase II, we allow doctors discretion to do a rescue and about 20% of the rescues in the Phase II didn't meet any of the criteria. Doctors just decided they wanted to do another injection. We're not allowing that in the Phase III. We also have a rescue criteria for new hemorrhage in an eye that is site-threatening due to wet AMD. That, however, we like the sites to adjudicate with a rescue monitor, meaning if they see a new hemorrhage, we'd like them to take a picture of it, and we have rescue monitors on call to talk to them within minutes about whether or not it's an appropriate rescue. And [ we'd ] say, well, why did you do it that way? Simple.

When Ramiro's team took a look at the rescues in the Phase II due to hemorrhage, there were 9 of them in all 3 arms total, 6 of them either didn't have a hemorrhage or the hemorrhage wasn't site-threatening or the hemorrhage wasn't due to wet AMD. So again, we'd like to minimize the number of rescues in the Phase III while not sacrificing vision and hence, the changes that I just spoke about.

So there are 2 Phase III trials, and they're kind of almost concurrent essentially, one in the readout. So just remind us when the readouts are expected?

So the first trial is called LUGANO. We announced last patient in the end of May. We expect the top line data release to be sometime mid-summer 2026. The LUCIA trial was several months later. We announced last patient in, in the end of July. So we should have about approximately 2 months between the top line from the 2 trials, both in 2026 in approximately 1 year or less.

And as you pointed out, it's a non-inferiority study, both are, and there's a margin, which you've talked about before. So obviously, you have to achieve that. What else, though, besides just hitting on the primary endpoint would kind of capture success for you for these studies?

Yes. In the end, I think it is rather simple. We need to be statistically noninferior to the EYLEA control arm and the non-inferior margin that we were given is minus 4.5 letters. In the Phase II, the lower limit of the non-inferiority margin for both study arms was around 2.6 letters. So we were very far from the minus 4.5 letters. In addition, we need to show continued safety. And that's one other big advantage that we've had. We've treated over 190 patients with our drug between 1 Phase I and 3 Phase II trials, and we've had no ocular or systemic SAEs attributable to the drug or the insert, and we've had no safety signals attributable to the drug or the insert.

So we're quite pleased with the safety. We did make an announcement just recently that our Data Safety Monitoring Committee had met in the Phase IIIs and recommended no change in the protocol. And at the same time, taking a look at the masked data from both trials, there doesn't appear to be any safety issue that would not be expected in a typical wet AMD trial. So that's the second thing, continued safety, which we're optimistic. And in addition, we need to show a reduction in treatment burden. In other words, compared to the EYLEA control arm, how many injections did the study arms get, and we need to show a reduction in that.

In the Phase II, the reduction in treatment burden was measured in several ways, and it was about an 80% reduction. That's really good. And if you ask KOLs, what type of reduction they'd like to see from a sustained release insert that's bioerodible, they'll tell you around 50% is good. We certainly hope to do better than that. But we think if we're non-inferior, safe and we have at least a 50% reduction in treatment burden, then we will have a very successful commercial drug.

So that sort of gets into how this would be deployed in the real world. What are you thinking in terms of the expected interval whether it's, as you point out, the reduction in the background use of one of the anti-VEGFs or if it turns out that you could even go as long as 6 months between the DURAVYU administration? How -- another way of asking it is just how do you see this being integrated into the management of wet AMD? I mean, we've talked about this before. There's many ways that could be done and different retina physicians are going to take maybe different philosophies. But so if you could kind of talk through that would be really good.

So I think, again, to get to review the data, we had about 2/3 of eyes make it 6 months -- up to 6 months after our insert went into Phase II without supplement. And with just one injection, we didn't repeat the injection of DURAVYU in the Phase II, 50% went a full year. So we know in a tough-to-treat wet AMD population, probably 50% of the eyes or maybe greater could go a full year with our drug. But we chose a 6-month interval for several reasons.

First of all, we're pretty confident that in humans based on animal data, that we will have a therapeutic level of vorolanib for at least 6 months in virtually everybody. We also believe by 9 months, the drug should be pretty much fully alluded in just about everybody. That 6-month interval gives doctors more flexibility. For example, if I have a patient who am treating with DURAVYU, and I'm watching them and at month 7, they get fluid. If we have a 6-month label, obviously, they can retreat with their DURAVYU. If we had a 9-month label or 12-month label, they couldn't. They wouldn't get paid to do it, be off label and the payers wouldn't pay for it.

So how it's going to get integrated into practice? I think at a high level, you can think about the same way that doctors treat wet AMD now. There's basically 3 strategies. The most overwhelming strategy right now is what's called treat and extend, which means you get the patient as dry as you can get them and you then try to extend out the interval between shots until you see fluid again and then you back off and that's called the fluid-free interval, and you pretty much stick with it. And most patients, at least in the short term, will -- can be adequately treated using that method. The problem is in the long term, patients still lose vision. They miss visits. They're probably still undertreated despite our belief in this strategy.

And so if you look at the long-term visual acuity results, the #1 reason why patients lose vision in wet AMD is undertreatment. So that's one strategy. The other strategy, which is rarely used now is called PRN or as needed, which means you see that patient every month, but you only treat them when you see fluid. The problem with that is you're essentially letting the eyes recur. And in wet AMD, recurrences are bad. We believe that if you continue to let fluid come back, patients lose vision. So unless the patient requests it, most doctors don't treat that way.

And then the third way is put them on a schedule. I think the pharma companies realized at the beginning that retina specialists like to individualize therapy and they don't read labels. And so it's very few who right now automatically usually sent us every month or use EYLEA every other month automatically or VABYSMO and high-dose EYLEA have 4-month labels. I don't think there's anybody that I know of who automatically goes 4 months. They need to -- the patient needs to prove that they can get out that long.

And if you look at the trials and look at the real world, 50% of patients on even VABYSMO or high-dose EYLEA still need treatment more frequently than every 8 weeks. So it's probably a patient-specific thing, not a treatment-specific thing. So putting someone on a schedule in that sense may not make sense. I actually think that may be the way we do get used more than the other 2 methods.

So if you look at our data from the Phase II and you ask the question, what percentage of patients could be treated with just our drug or 1 or 2 EYLEA for a year. Now again, we need to extrapolate because obviously, we didn't reinject in the Phase II. But if that data holds, you could treat 90% of patients a priority by altering your treatment every 3 months with 2-milligram EYLEA and DURAVYU. Make it really simple, just put everybody on a schedule.

You know exactly when they're going to come in, you might be overtreating some patients, but I think they're using the 2 MOAs in this fashion because vorolanib does have a different MOA, I think that would be advantageous. So I think going back, it's a long answer to your question. You're going to see all 3 of those methods used to doctors get comfortable with how our drug works in the real world.

And another important real world question is a pharmacoeconomic one, obviously, which is price. So anything you want to comment on that? Or is it a bit too early to say much?

Maybe a little too early to say much, but I think the simple way if you're modeling the pharmacoeconomics is to think about if the studies hold, 1 DURAVYU is approximately equivalent to 3 EYLEA. And we would expect that, that's a model that could be used as a baseline to model the cost. If we have additional benefit and the additional benefit would be, we hope, better treatment outcomes in the long term. We may also see additional benefit. We've got some preclinical data that suggests that our drug is neuroprotective.

It may also be antifibrotic because we block PDGF. And it also may lead to less atrophy, which all of these 3 things we're going to be looking at in the pivotal trials. So if we can show any of those things, I think that we would be able to price it even more of a premium.

By the way, I should have clarified before those 2 studies, LUGANO and LUCIA, they're essentially identical trials, correct?

They are essentially identical. I think the only difference is PK sampling from the serum. That's it.

That's it. Okay. Okay. And of course, you -- I think you've made the statement in the last several quarters that you now expect to be -- you expect to be first to file amongst the other companies that are developing these long-acting inserts. Is that sort of still an accurate statement?

I think it's quite accurate. And every day that passes increases my confidence in that statement. To go back in time, we dosed the first patient with DURAVYU a little over 4.5 years ago in a Phase I. So we've subsequently done 1 Phase I, 3 Phase IIs and fully enrolled 2 Phase IIIs in about 4.5 years. So we've executed really well. But going back 4.5 years ago, we were in last place. There was a race of multiple companies trying to do sustained release in wet AMD.

We're now lapped the field, and we strongly believe we're in the first place. Why? Because we're going to have last patient out of next summer. And we should be able to file, we hope, by the end of next year. And even with a standard type of review, which we hope will be eligible for a quicker review, we're optimistic that we should be able to launch this drug, if approved, by the end of 2027. Our nearest competitor, they're all still enrolling their Phase III. And so when you do the math on when they're likely to finish their second trials, we think we're at least 6 months, if not a year ahead of the nearest competitor.

Let's talk a little bit about another sort of commercial topic, which is super important, and your manufacturing facility is just down the down the street figuratively speaking...

Not in a high-rent district here. No, we're not on Newbury street. It's a little more than down the street. It's in Massachusetts.

So tell us about the CGMP facility and what the capacity is there? And how much of the market you could supply?

So first of all, we don't believe we have any exposure to tariffs. We manufacture this here in the United States. As Yigal said, it is not right down the street. But if you drive an hour west of here, you'll see a very nice Bucolic town called Northbridge, Massachusetts, and that's where our facility for manufacture is. Our API is also, by the way, made in the United States.

Northbridge was conceived about 4 years ago when we realized that if we were going to be successful, we would need a commercial facility dedicated to making these inserts. It's 41,000 square feet CGMP for both Europe and the United States, 8 large clean rooms. And at capacity, we believe we should be able to make close to 1 million inserts a year in this facility. That should be able to supply even -- well, maybe not our wildest expectations, but let's call, above our base case expectations, should easily be able to supply the entire world with these inserts.

We are in the midst of preparing for a potential launch by upgrading the facility, getting it ready to go 5 or even 7 days a week with 2 shifts. We are in the midst of doing registration batches there now and preparing, of course, for the FDA inspection for preapproval. So all of this, again, is all mapped out and so far on target, and we're quite optimistic that not only will the facility be acceptable to the FDA, but it will be able to supply us and the world with enough of these inserts to be quite successful.

And can you describe to everyone listening and here in the room, just how does this actually work with these inserts because obviously, with the traditional anti-VEGF, it was -- you draw it up from the vial, but here you have physical drug delivery device. So how -- what is the structure of that injection? And how does the physician do it?

Sure. So I mentioned that we had 4 FDA-approved products prior to DURAVYU. And essentially, what we can do is take the API and put it into a matrix that holds the API together. All the prior approvals, the API was very soluble. So if you just injected it as is into the eye, would go really fast. So we needed to wrap it in a non-erodible shell made of polyamide and the shell had pores and that allowed the drug to diffuse out. DURAVYU does not have polyamide. There is no shell to it. It's all drug and matrix.

And in fact, we've been able to make process improvements so that the inserts now are 94% drug, only 6% matrix. So at 9 months, the drug load should be completely spent. In that matrix, we designed it so that the matrix would hold the drug together for the -- until the drug load is gone because you need to control release till the end. You don't want free floating drug particles in the eye. That matrix is fully bioerodible and should go away in several more months.

So there are [ cylindrical ]-shaped inserts that are preloaded into a sterile syringe injector. It's actually quite simple for the doctors. It's shipped and stored at room temperature. It doesn't have to be frozen or refrigerated like our competitors. It does not contain any PEG. If you had followed some of the issues around the potential of PEG causing inflammation in eyes, we don't have PEG. We also don't have PLGA. So the studies that we've done preclinically and obviously, I talked about the clinical studies have really shown no safety issues at all.

So it's quite simple, shift and sort of room temperature, open up the package, take off a cap, take out a wire, remove another cap and you're ready to go. And one of the interesting things we've learned as we've really prepared the market for potential approval is that even the large retina groups who one would think is really concerned mostly about cost and the potential for fewer injections, that's not their #1 concern. Their #1 concern is don't slow down our doctors. Don't have a product that requires mixing, defrosting or obviously get a J code as quickly as possible, which we know all about in order to be commercially successful.

So that idea of not interfering with the flow of these busy retinal clinics, we think we hit that bill really, really well.

And speaking of this practice dynamic of not slowing down the physicians in terms of the overall use of the anti-VEGFs, and we've gotten this question, and I probably asked you this question before, but some investors have asked, does it -- would it impact the overall use of the anti-VEGFs? You mentioned the 3 different approaches. It sounds like a lot of that would -- there'd be a lot of averaging out, so to speak, in terms of use of EYLEA or Lucentis and it wouldn't really change that in a sense. Is that fair or...

I think it'd be fair to say that there would be some patients whose -- if we're successful, whose usage of the other branded drugs would be less. How many doctors and patients choose to go every 6 months on our drug alone remains to be seen, even though it looks like again if the Phase II data holds, about 2/3 of the wet AMD population probably could be managed with our drug alone. But the idea of using a second MOA together, that's really been part of medicine in chronic disease treatment all over the body for years.

And in ophthalmology, you look at glaucoma therapy, they mix drops with different MOAs all the time. So ophthalmologists are used to this idea of 2 MOAs. Doctors have no lack of patients needing injections right now. They want more flexibility in their ability to control the rate of injections and especially with the rise in the anticomplement drugs, there is just so many injections that need to be done out there. There's also pressure in the retina community to continue to be the deliverers of injections in the United States.

If the volume can't be handled by retinal specialists, there's a worry that non-retina specialists would become the main deliverers of the injections. And that's something that I think the retina community is cognizant of and truly believe that it should be in the retina specialists' hands because they're the best ones to be able to judge the efficacy of the injection as well as deal with any potential complications.

So again, a long-winded answer to say it doesn't seem to be an issue around retina specialists feeling like this is going to be taking away injections from them. They're not worried.

And so you mentioned the capacity globally. What -- the study -- the 2 Phase IIIs, could they support or what is the plan to support the filing in Europe or even other territories?

So we did announce that the EMA did approve our protocol, and we did have European sites in the second study. Approximately 20% of the second study was enrolled OUS, enrolled very rapidly, again, showing how excited the doctors outside the U.S. were about the possibility of fewer injections. That also because EMA approval of a protocol, obviously, it doesn't guarantee that you get approved as a product, even if you have positive data, but it is a closer step for that and that the EMA, my understanding is that they not just look at is the protocol safe, is it likely to show good data, but is this a potentially approvable product in Europe? And we believe with good data, we will be approvable there as well as the rest of the world.

So the filing for Europe would be staggered or how well...

Strategically, we're in an interesting time right now in that we know that our value is primarily in the United States, and we are confident that we can launch this drug ourselves successfully in the United States. What our European strategy will be, I think, will also depend on some of the external things that are happening in the world. And we will be prepared from a regulatory situation to have a launch in Europe. Whether we do launch all across Europe or get a partner to do that or only selectively launch in certain countries, those are all options that we're weighing at this point. So we will be prepared for us or potentially a partner to launch OUS.

Okay. Let's shift gears a little bit because you have also done work in diabetic macular edema, DME. So can you just summarize the data that we've seen there? And I know that there's the potential to start a pivotal, but you're not quite pulling the trigger on that yet. So explain the reasons for that and when you might be willing to go in that direction.

Sure. Well, the DME trial is a Phase II, the VERONA trial, we tested -- this is the first trial that we did the higher payload insert in. So we tested 2 doses, 2.7 milligrams and 1.3 milligrams against EYLEA control. This is the first trial that we did where all the patients had active disease. In fact, they couldn't be enrolled unless they had fluid and they had decreased vision, and they couldn't have received an injection within 2 months of enrollment of screening.

So based on the excellent results we got, we're very confident in our drug's ability to treat DME because this was all an active population. The primary endpoint was time to first rescue, which both arms of DURAVYU did better than the EYLEA control. But also from a visual acuity perspective, one of the really fascinating things is both arms of the DURAVYU showed significantly better vision and significantly better drying effect at 4 weeks than EYLEA did.

So if this holds, if we can be non-inferior to EYLEA, but we can get the same result EYLEA gets, but it takes them 5 or 6 months to get the patients dry and better vision, and we can do it in 4 weeks, we are going to have a huge competitive advantage.

If you look at the subgroup analysis from the VERONA trial, just look at the patients in the high-dose 2.7 milligrams who didn't receive a supplement, it was over 70% did not. They gained well over 10 letters, and EYLEA usually gains naive about 8 letters. And they had 120 microns less fluid. So there is really a significant drying effect in this population that correspond with the improved visual acuity, giving us, again, confidence that this drug works really well in an active DME population.

With respect to the pivotal trials, we are really focused on wet AMD right now as a company. And we want to make sure that given how well things are going with the wet AMD trials and how well things went with the Phase II that we make sure that we do not put any of the wet AMD aspect of the company at risk, which means if we said -- as we said publicly, we do expect to run a pivotal program in DME, and we expect the first patient to be dosed sometime in 2026.

We've had a successful end of Phase II meeting with the FDA, and we're quite pleased with the way things came out. And we will, later on this fall, update about the type of protocol that we're going to run in DME, but first patient will be a '26 event.

Anything more specific you want to convey on the end of Phase II meeting in terms of what they suggested regarding the [indiscernible] study?

Again, I think more specifically, we have said this, the end of the trial can be significantly less than wet AMD. And the agreement around control group, once again, the FDA reiterated, if you want to do a non-inferiority trial, you must do it against on-label EYLEA, which means randomization on day 1 before the first EYLEA dose is given. And that's what we -- our expectations were, but they did reiterate that.

Okay. And in order to do that, would you need to raise additional capital? Or what's the -- George, maybe you can chime in on that part.

Yes. So our current cash guidance is into 2027. It does exclude the actual trial costs for DME. And so I think between now and sometime into Q1, we'll have sorted out, and it will be part of our design and plan and how we talk about the Phase III pivotal design.

Okay. But there are other some other retinal diseases that you have looked at as well beyond the 2 we've discussed. So can you comment on those and PDR, for example, there are others?

Yes. So we did a trial in NPDR, nonproliferative diabetic retinopathy, which is a disease that does not typically carry a decrease in vision. There's no edema. There's no vitreous hemorrhaging with NPDR. And there are 2 approved products, Lucentis and 2-milligram EYLEA are both approved for NPDR, but almost nobody uses them. The market penetration is about 2%.

And the reason is frequent injections and the fact that doctors are optimistic that should a patient show a site-threatening complication like the development of DME, then they can just treat with anti-VEGFs at that point. Our trial did show a reduction in the number of patients who got worse DME, but we didn't hit the primary endpoint. The primary endpoint was improvement in NPDR based on the fundus photograph. So given that result, it's not that we probably couldn't get a label for NPDR using another endpoint. But given the market size, the size of the study that we needed to run, we made the conclusion that from a financial perspective, it didn't make any sense to continue with an NPDR program.

Okay. And now as far as catalysts and other things, of course, everyone loves catalysts. You've already talked about the big one, which is the Phase III data that's coming next summer. But ahead of that, what are the sort of intermediate updates might we get? What's your presence going to be at some of the eye meetings, just to fill in the gap between now and the big deal?

I think we're going to have great presence at eye meetings, including Retina Society in 2 weeks where we're going to have a little bit more of the DME data to show. The EU Retina Meeting is occurring starting tomorrow. And later in the week, I'll be off there. We have some presentations at the EU Retina Meeting as well. Other catalysts include we will -- or we plan on updating the safety after the DSMB meets again, we'll give some update on safety.

And probably at the beginning of next year at some meetings, we will start to show some of the pool demographic data of the Phase III trials. At some point this fall, we do expect to talk more about the DME program and give a little more color around the actual study design and when we expect to dose the first patient.

That reminds me of something else. You mentioned pooled. So when you show the data for LUCIA and LUGANO or LUGANO and LUCIA, I guess, is the order, is it going to be all at once? Are you going to have each one separately? Or is that TBD?

We're planning on doing them separately. No reason in our mind to hold the LUGANO data once we know it. And given how soon the 2 studies are together, we think that there's advantage to really show them one at a time.

And then once you have one -- can you -- is it going to be like a rolling BLA? Or you just wait to do both? Or how does that work?

Technically, when you say rolling NDA, we may or may not have permission from FDA to do what they'd call a rolling submission. But we're rolling the preparation now. We have some of the modules written already because they're preclinical and the data is not going to change. We know what they are. So from an internal perspective, we're rolling the preparation. And this gives us another advantage because assuming LUGANO is positive, I think it's highly likely LUCIA will be as well, given that they're identical trials.

So we can start to write the clinical modules from the LUGANO data, and that is dumped the LUCIA data in, which I believe will give us another kick start to getting the NDA in quickly.

Awesome. All right. Well, thank you again. Great progress. Appreciate the time, both of you. We look forward to the meetings and then the data, of course.

Thanks, everybody, for listening.

Thanks very much.

Good morning. My name is Antoine, and I'll be your conference operator today. At this time, I would like to welcome everyone to the EyePoint Second Quarter 2025 Financial Results and Recent Corporate Developments Conference Call. [Operator Instructions] Please be advised that, this call is being recorded at the company's request.

I would now like to turn the call over to George Elston, Executive Vice President and Chief Financial Officer of EyePoint.

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's second quarter 2025 financial results and recent corporate developments.

With me today is Dr. Jay Duker, President and Chief Executive Officer of EyePoint. Jay will begin with a review of recent corporate updates and discuss the ongoing clinical trials for DURAVYU in wet-AMD. I will close with commentary on the second quarter 2025 financial results, and we will then open the call for your questions.

Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of the release can be found on the Investor Relations tab on the company website, www.eyepointpharma.com.

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, financial projections and our plans and prospects.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we may have made or may make with the SEC in the future.

Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today.

I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of EyePoint.

Thank you, George. Good morning, everyone, and thank you for joining us. I am delighted to discuss with you today our key second quarter updates highlighted by the impressive progress of our Phase III clinical program for our lead asset, DURAVYU, in wet age-related macular degeneration or wet-AMD.

Since January 2021, when the first patient was dosed with DURAVYU in our Phase I DAVIO trial, our diligent focus and exceptional execution across all fronts has brought us in just over 4.5 years to full enrollment in both of our Phase III pivotal trials in wet-AMD, a testament to EyePoint's leadership in drug development and commitment to serving the retinal community.

Before discussing the specifics of the past quarter, I'd like to reflect on how far we've come as a company over the short period. We successfully and efficiently pivoted to a clinical stage biopharmaceutical company, prioritizing the development of DURAVYU as a new treatment paradigm in the 2 largest retinal disease markets, wet-AMD and diabetic macular edema, or DME, while exiting the specialty pharma business.

We completed 4 clinical trials for DURAVYU, including 3 Phase II trials, treating over 190 patients with DURAVYU across multiple retinal indications, establishing a robust and favorable safety profile that is cited by physicians as a key motivator for their eager participation in our pivotal program.

We've generated the most comprehensive data set among current sustained release therapies in development for wet-AMD, establishing truly compelling Phase II efficacy data, demonstrating statistically non-inferior visual acuity compared to on-label aflibercept, while reducing treatment burden by over 80%.

Bolstered by this robust efficacy profile, outstanding safety and a patient-centric pivotal trial design, we completed oversubscribed Phase III enrollment in record time for this indication, with over 800 patients enrolled across the LUGANO and LUCIA trials.

Thanks to rapid enrollment and efficient trial design, we are well positioned for top line LUGANO data in mid-2026 with LUCIA top line data anticipated shortly thereafter, a timeline that we believe positions us to be first to file, and potentially first to market among the current investigational sustained release therapies for wet-AMD.

We also expanded the database underpinning DURAVYU's differentiated clinical profile beyond wet-AMD, reporting highly positive results in the Phase II VERONA trial in DME, supporting a pivotal program in this second blockbuster indication. In anticipation of potential commercial success, we built a state-of-the-art 41,000 square foot cGMP manufacturing facility in Northbridge, Massachusetts to support commercial production of DURAVYU, with registration batches currently underway to support an anticipated NDA filing and eventual pre-approval inspection.

Finally, we transformed our balance sheet by eliminating debt and extending our cash runway into 2027, well beyond pivotal wet-AMD data in 2026. I'm incredibly proud of the pace and quality of these achievements, and we have no intention of taking our foot off the gas.

Now for a closer look at wet-AMD. This is a $10 billion market and growing in the United States, currently dominated by a single treatment modality, monotherapy with anti-VEGF biologics. While efficacious, patients with wet-AMD still tend to lose vision in the long term.

Newer options intended to provide up to 4 months of visual stabilization in some patients still have similar limitations and often require significantly more frequent injections to maintain stable vision. In light of these drawbacks, improved durability remains the most important factor for physicians when choosing a wet-AMD therapy and represents an area of much needed innovation.

Our lead product candidate, DURAVYU, presents a compelling treatment paradigm shift paired with a new mechanism of action to meet this need. Backed by durable efficacy of at least 6 months, and a consistent and favorable safety profile, coupled with unique storage and administration advantages, we believe DURAVYU offers a differentiated product profile that is meaningful to physicians and patients and if approved, would facilitate strong competitive positioning in the wet-AMD treatment landscape.

Let me now walk through the key attributes underpinning DURAVYU's differentiation. First, DURAVYU is not another anti-VEGF biologic or ligand blocking therapeutic, like the approved products on the market. It's a clinically validated sustained-release tyrosine kinase inhibitor, or TKI, that brings a new mechanism of action that may complement existing anti-VEGF biologics to offer more durable disease control and a reduced treatment burden.

DURAVYU is comprised of the potent and selective TKI vorolanib, which works intracellularly to inhibit all VEGF receptors as well as the PDGF receptor, formulated in our bioerodible Durasert E technology. Durasert E is a next-generation bioerodible sustained release insert, with a matrix designed to prevent free floating drug particles that contains no PEG and no PLGA.

Second, unlike other sustained delivery therapies in development, DURAVYU is shipped and stored at ambient temperature. Consistent with current practice, DURAVYU is administered in the physician's office, with a standard intravitreal injection and comes in a preloaded sterile syringe injector.

Most importantly, through its novel mechanism of action, DURAVYU can potentially deliver stable vision and retinal anatomy when dosed every 6 months, a cadence that should support improved compliance over the long term for wet-AMD patients. The clinical data generated to date indicates that DURAVYU has the potential to meaningfully change the wet-AMD treatment paradigm, and we've designed our Phase III program to validate this through a clinically rigorous but derisked approach.

Our Phase III LUGANO and LUCIA trials are double-masked, noninferiority trials designed in close alignment with the FDA, including written agreement from the agency to support a clear approval pathway and a compelling label. In addition, the patient-centric design of the trials allows all patients to receive treatment with the goal of maintaining or improving vision. The trials leverage an established design to measure noninferiority against on-label 2-milligram aflibercept.

The use of on-label standard of care as the control is a key component of FDA guidance and critical to the noninferior design of the trials. Importantly, retinal specialists are familiar with leveraging non-inferiority trial data to inform their prescribing decisions as the last 4 wet-AMD approvals in the United States followed this approach.

Furthermore, the inclusion of both treatment-naive and previously treated patients enhances the applicability of our data and can enable a potentially broader label that would help drive increased physician adoption. If approved, our label is expected to have a differentiated 6-month dosing interval -- this would be a significant improvement compared to current anti-VEGF treatments in the United States, which are dosed on average every 2 months.

Driven by the clear market need for more durable wet-AMD therapy, DURAVYU's patient-centric trial design, robust and compelling Phase II clinical data package, and a record of excellent safety across the full clinical development program, we enrolled and randomized over 800 patients in LUGANO and LUCIA trials.

LUCIA also marks our global expansion with sites in South America, Europe, Israel, Australia and India, demonstrating continued momentum and demand across the global wet-AMD patient community for DURAVYU. We are proud of the clinical rigor of our Phase III program, underscored by the fact that both the FDA and the EMA, the 2 largest regulatory agencies in the world have signed off on the protocol, and we have exceeded our enrollment time lines with no major changes to our trial design.

With the 56-week primary endpoint for both trials, we anticipate LUGANO top line data in mid-2026 with LUCIA to closely follow, giving us confidence in our first-to-file and first-to-market position among current investigational sustained release therapies. The consistently positive feedback from physicians and patients continues to strengthen our conviction in DURYVU's differentiated profile and eventual commercial success.

As part of the efforts to maintain first-mover advantage, we have made significant strides in our commercial readiness, while remaining disciplined in our investments. Our state-of-the-art cGMP commercial manufacturing facility in Northbridge, Massachusetts is designed to meet future commercial demand.

In support of a potential NDA filing, DURAVYU registration batches are underway. Additionally, we thoughtfully added to our organization, expanding key areas, such as late-stage clinical development, regulatory, pharmacovigilance, biometrics and medical affairs, all while maintaining fiscal discipline.

While our top priority is advancing our wet-AMD program through top line data and an NDA filing, we are also excited to report our continued progress in DME, the second largest retinal disease indication. Affecting approximately 25% of diabetic patients, DME is estimated to represent a $3 billion market opportunity by 2030 in the United States.

Like wet-AMD, the significant burden of regular anti-VEGF injections often results in missed doses and lost vision, suggesting the need for more durable therapies. Following the compelling safety and efficacy results of our Phase II VERONA trial in DME earlier this year, we had a positive end of Phase II meeting with the FDA to align on a future pivotal program. We look forward to sharing more details on our pivotal plan in the upcoming months.

In summary, with top line Phase III data for both LUGANO and LUCIA on track for readout in 2026, and urgent and growing need for safe, effective and more durable treatment options for wet-AMD and DME, EyePoint is well positioned to continue as the leader in sustained release drug delivery for retinal disease as we partner with the retinal community to improve patients' lives while creating long-term value. Our decades of clinical experience, next-generation technology and blockbuster potential of the DURAVYU franchise highlights our exciting growth story.

Before passing it over to George to review our financials, I want to thank the entire EyePoint team for their commitment to our goal of improving patients' lives through better vision, as well as the patients and the clinical investigators outside of our organization who are participating in our trials. We deeply appreciate your confidence in us, and we are proud to advance our therapeutics for the benefit of the entire retinal community. We look forward to continued progress towards our upcoming milestones as we further our leadership in sustained ocular drug delivery.

I will now turn the call back over to George. George?

Thank you, Jay. To begin, we continue disciplined financial management and good stewardship of our cash, ending the second quarter with $256 million in cash and investments.

Of note, as Jay just mentioned, the rapid enrollment of over 800 patients in the LUGANO and LUCIA trials accelerated our planned use of cash into the first half of 2025. The trial enrollment was well ahead of our expectations and the associated burn is included in our plan and cash runway guidance.

Now that we have completed full enrollment for both trials, we expect cash burn to meaningfully decline in the second half of 2025. Accordingly, we affirm previous cash runway guidance and expect cash will support our operations into 2027 well beyond key data readouts for our Phase III wet-AMD program in 2026.

As the financial results for the 3 months ended June 30, 2025, were included in the press release issued this morning, my comments today will focus on a high-level review for the quarter. For the quarter ended June 30, 2025, total net revenue was $5.3 million compared to $9.5 million for the quarter ended June 30, 2024.

Net revenue from license and royalties for the quarter ended June 30, 2025, totaled $5.3 million compared to $8.4 million in the corresponding period in 2024. The decrease was primarily driven by lower recognition of deferred revenue related to the agreement to licensed YUTIQ product rights completing our exit from Specialty Pharma.

Operating expenses for the quarter ended June 30, 2025, totaled $67.6 million, compared to $44 million in the prior year period. This increase was primarily driven by the increase in clinical trial costs related to the ongoing Phase III LUGANO and LUCIA clinical trials of DURAVYU for wet-AMD.

Net nonoperating income totaled $2.9 million and net loss was $59.4 million, or $0.85 per share compared to a net loss of $30.8 million, or $0.58 per share for the prior year period. As I noted earlier, cash and cash equivalents and investments in marketable securities on June 30, 2025, totaled $256 million compared to $371 million as of December 31, 2024. And again, we affirm cash guidance unchanged into 2027.

In conclusion, we're incredibly pleased with EyePoint's progress so far in 2025 and remain well capitalized to deliver DURAVYU Phase III data in 2026.

I'll now turn the call back over to Jay for closing remarks.

Thank you, George. As you've heard this morning, we ended the second quarter in a phenomenal position, and we remain focused on advancing DURAVYU, a best-in-class program in wet-AMD. With our strong balance sheet and clear development strategy, we are prepared to execute through our upcoming key milestones, including top line data for the Phase III LUGANO trial anticipated in mid-2026, with LUCIA to closely follow.

An NDA submission for DURAVYU in wet-AMD, assuming positive data and continued updates on the DME program, including a presentation of the Phase II VERONA end-of-study results at the Retina Society Annual Meeting in September.

Our 2025 progress to date reflects our dedication to advancing our pipeline and delivering innovative treatments for serious retinal diseases, and we are excited to continue our momentum throughout the second half of the year. Thank you all very much for your attention this morning.

I will now turn the call over to the operator for your questions.

[Operator Instructions] Our first question comes from Tess Romero from JPMorgan.

So maybe you could speak a little bit to overall trial conduct of these 2 pivotal studies in wet-AMD and what you're really focused on getting right to mitigate any key risks.

Thanks for the question, Tess. Nice to hear from you. That's really a question I think Ramiro, our Chief Medical Officer, can answer best because this is obviously what he is now focusing on and will be focusing on over the next year, given that we are now fully enrolled. So Ramiro, do you want to take that question?

Yes. Thanks for the question, Tess. And I think one advantage that EyePoint has is that, we have a strong large Phase III study that gave us a lot of experience on the conduct of studies with our 1901 DURAVYU. So as Jay mentioned, we executed really well on the enrollment, completed the enrollment for both studies ahead of time. And now the focus is on the study conduct.

So of course, we are -- have a collaboration very closely with the clinical sites, with the investigators to get and make sure that there is no deviations on this protocol. We also, of course, track safety of our patients in the study, which is very important. We have a good collaboration with our CRO that help us conduct the study. So now it's all about making sure that we have a great execution over the next 12 months, and then study preparation for our top line results with on-time database lock and other activities that are necessary for the top line results.

And maybe if I could add just a little bit more about our protocol. Once again, this noninferiority trial design is something that retinal physicians are really used to. Our control group is on label. And the study design, again, is simple for the sites and the patients to understand. So, I think all of this helps keep patients in the trial. And our dropout rate is quite low in both trials, less than 2% currently. So, from that regard, we're doing really, really well also.

Our next question comes from Jennifer Kim from Cantor Fitzgerald.

Congrats on the continued execution, the delivery and consistency of these trials has been refreshing to see. Maybe to start off, I know you said you've talked about not disclosing certain mask data in the Phase IIIs and avoiding introducing operational bias. Is there a line that would concern regulators in terms of introducing bias? And are you able to say anything on the cadence of, say, supplemental rescues as far as whether they've stayed within expectations? Maybe we can start there.

Yes. Good question, Jennifer. Thanks for that. So I think at a high level, talking about masked demographics such as age, sex, OCT visual acuity of the patients that have been enrolled is not really any risk. And we will likely do that in the future prior to top line data.

On the other hand, what we wouldn't want to do is introduce bias that would cause investigators or patients to alter their behavior. There really isn't any reason for us in my mind to put that risk into our trial results at this point. So, while we may, under circumstances in the future, rethink this, right now, things are going so well that we wouldn't want to introduce unnecessary risk into the studies. And once again, Ramiro, if you want to give a little more color on that or any more detail, please feel free.

No, I think you covered well. And of course, we have a lot of the mechanics to make sure that the safety of the patients is going well, including an independent data monitoring committee that assess the safety of our study on an independent matter. And we issued that press release included that information that the safety of whichever brand is going as we expected as well as our Phase II study. But as Jay mentioned, we want to make sure we don't introduce unnecessary bias in the study that is going so well so far.

Okay. That's helpful. And my second question is actually related to that. Should we expect a regular cadence of safety updates like on a quarterly or some periodic basis?

Well, I think we will give periodic updates. We haven't really discussed internally, will there be a cadence. We'll cover that in the future. And yes, I think it's quite likely that we will give periodic updates to the safety database as we hear from the Data Safety Monitoring Committee.

Our next question comes from Tyler Van Buren from TD Cowen.

Congratulations on the tremendous enrollment for both LUGANO and LUCIA. Can you just elaborate on the rescue criteria for the trials, especially given the recent competitive updates and how that aligns with what is seen in the real world?

Thanks for the question, Tyler. I'll actually address the second part of your question first. And again, if you talk to retina specialists and you ask them about the supplemental criteria in any one study, their first reaction is, well, that's not what I do in the real world. And the issue is that in the real world, giving an additional injection is something that is very much individualized to the patient. What's their vision? How is the other eye doing? Do they notice a change? A myriad of things that individualize treatment for patients. But for a study, you can't do that. You need to have strict guidelines, especially in a pivotal program about when a rescue or supplement injection is given.

So, as we have disclosed publicly in the past, our Phase III supplement criteria, we think, is very straightforward. If a patient loses more than 5 letters with 75 microns of new fluid over best on study due to wet-AMD, they should be rescued. And that's been consistent from the start of the trial, we haven't amended that.

In addition, we have a second criteria, which is new site-threatening hemorrhage that is caused by wet age-related macular degeneration. And we've set up a system that's working, we think, quite well with injection monitors, and we've asked the sites to call one of these monitors, and they've been excellent about getting on the line with the sites right away to discuss potential rescue over a hemorrhage. And that needs to include a fundus photograph.

And the reason we did that was when we looked at our Phase II data, in the DAVIO 2 wet-AMD trial, there were 9 patients who were rescued in all 3 groups total for hemorrhage. Well, when we looked at the fundus photographs and the clinical situation with our KOLs and our advisers, 6 out of 9 of those eyes either didn't have a hemorrhage or the hemorrhage was not due to wet-AMD, or was not site threatening. So, we really want to only rescue the patients who need it and are going to benefit from it and not rescue patients who do not.

And therefore, again, this was Dr. Ribeiro's evaluation of the rescues in the Phase II. We don't have a criteria for fluid alone. We don't have a criteria for visual acuity loss alone, because in those situations, what we saw in the Phase II is a rescue injection didn't help. And in the Phase II, 20% of the rescues were not per any of the protocol rescue requirements. They were due to the physician discretion. And we've removed physician discretion in the Phase III.

Our next question comes from Yigal Nochomovitz. Yigal? Our next question comes from Yatin Suneja from Guggenheim.

Maybe 2 quick ones for me. With regard to the baseline, could you just comment on what percentage of naive and exposed patients you are targeting and where did you end up? If you can just talk about that on a high level. And then switching to the commercial dynamic, could you just talk about your early commercialization strategy, what work you might be doing now? What type of patients can we address? And how should we think about the overall commercial team.

Thanks, Yatin. Nice to hear from you. First of all, with the baseline division between patients who were previously treated and who were naive to treatment, we sought to get about a 75%, 25% naive to previously treated ratio, and that's in fact, what we achieved. So, 75% of the enrolled eyes were naive.

With respect to commercialization, we've had an early product commercialization team on this essentially since the beginning of our Phase II DAVIO 2 wet AMD trial. And they have been working diligently, not only in, let's say, preparing the market, which I think they've done a very good job in raising physician awareness of what a TKI is and how it's differentiated from our current therapies, as well as how a sustained release delivery system like Durasert E can be advantageous for small molecule delivery. But they've also been in discussions with payers and with administrators of both large and small retinal practices in the United States and out of the United States to get a feel for how we can set the stage for us to be successful in the marketplace.

So, this has been an extensive broad and deep effort that we've done and we'll continue to do. And we are planned and budgeted to start to build our commercial team in more breadth and depth later this year in anticipation of a successful NDA and potential launch, we hope at the end of 2027.

Maybe one more, if I can follow up. Just on the naive versus exposed patient, are there special consideration for how we should think about the rescue rate or the injection fee rate, at least on the control arm for these naive versus the exposed patients? Just curious how that dynamic will be between these 2 subsets.

That's a good question, Yatin. And I don't think we can actually know that yet. we expect that the rescue rate for naive patients will be less than what we saw in the DAVIO 2 Phase II trial. The reasoning is in the DAVIO 2 trial, while they were all previously treated patients, the vast majority of them were being treated often, as we like to refer to them as frequent flyers.

On average, those patients had received 10 injections normalized of the year leading into the study. And in the United States, we specialists average about 6 injections per year. So, this is a group of patients that needed a lot of treatment. Yet we did pretty well with them. We got very few patients who had already been treated and extended out 3 months or longer. They just didn't enroll in that trial.

Now our assumption, and I think it should be clear to everybody that, if we have a patient who can be successfully treated and extended out to 3 months or longer on any of the current agents, our drug, DURAVYU should do really well with those patients. So, we wanted to get a portion of them into the trial. And depending on who you talk to, this could be 20% or 25% of the wet AMD naive population. So, we think that by enrolling a predominantly naive population, we should see fewer supplements, and we hope to see, therefore, better visual acuity results.

I will like to remind everyone that, if you looked at the patients in DAVIO 2 that did not get supplemented, they made it through month 8 with no supplement, their visual acuities were numerically better than the Eylea control group. So, the unsupplemented patients seem to do exceptionally well with our drug, and we hope and expect that will continue in the pivotal trial.

Our next question comes from Yigal Nochomovitz from Citigroup.

I had 2 questions. One on the endpoint. There's been some chatter in the marketplace with respect to the blended versus the single time point. I'm just wondering, if you could comment, Jay, on that point. And is this a detail that the retina professionals really even care about whether you happen to average 2 very close points in time versus a single point in time?

And then also just looking ahead to the potential launch, assuming everything goes well with the studies, is this a situation where once you get to the label, you can just launch immediately? Or is it a situation where you would wait until you have the label language in hand and then there'd be a period of time where you have to do the final fill and finish label printing and so forth and then launch some period of time after actually the PDUFA?

Great. Thanks, Yigal. Two good questions. So, the blended endpoint was a regulatory, let's call it, strong suggestion. In fact, in our 2022 Type C meeting on our pivotal program, they insisted on it. And that's why we did a blended endpoint in our Phase II trial. This was reiterated again at our end of Phase II meeting in 2024 with the agency. And so, we obviously put that into our trial.

We think the blended endpoint is a good thing. We think it decreases variability, and it decreases the risk of missing your primary endpoint. This blended endpoint also will help ensure that there is no missing data at the end of the trial. Obviously, if a patient makes one of those 2 blended visits but misses the other, there's a way we statistically handle that versus if they miss the single endpoint entirely.

So overall, the agency strongly suggested it, and we did it, and we're very happy that we did it. And we think this is another point of our protocol that is derisking. In addition, I have to add the blended endpoint has been used in most recent studies. This isn't new or unique.

So, your second question about timing of launch. At this point, should our trials be successful and our NDA approved, we are working diligently towards an immediate launch after approval.

Our next question comes from Debanjana Chatterjee.

So with the first readout expected in mid-2026 and the second to follow shortly after, could you give us like any more color into your regulatory plans on how you'll gather the data and how soon you can submit? And maybe could you also comment on the scope of the safety package that the FDA would like to see with the initial filing?

Sure. Thank you for that question. So now that we are fully enrolled in both studies in record time, Ramiro and his clinical group are really focused on ensuring that the data is sound, as we discussed earlier, and preparing for the NDA submission.

So again, we expect top line data from the first trial to be summer of next year with the second trial, again, to follow shortly. I'm going to let Romero talk about some of the efforts around rapid NDA filing that we are working on.

Yes. Thanks for the question. As Jay mentioned before, our expertise and our strain is on the execution. So, the same way that we were able to execute rapidly on the enrollment, our aim is also to make sure that we do an NDA ahead of schedule. We have 2 identical non-inferiority studies. And this really gives the benefit of looking at the results from the first study from LUGANO doing some learnings there. And then when we get the results from LUCIA, be able to accelerate the interpretation and the write-up of those results, again, because both studies are identical. We should assume that the result of LUGANO is going to be replicated on LUCIA.

In terms of the safety package, as any other NDA submission, this is going to include the results from our Phase I, Phase III study as well as the combination of the Phase III program. And we should have enough patients to meet the requirements for the FDA for this type of indication.

And I just want to elaborate a little bit more on what Ramiro just said about numbers. So, the FDA has been clear for years about wet-AMD safety database. You need to have 300 evaluable patients at the dose and the interval that you want on your label. And if you come in with 299, it will not be accepted. That's why if you look at the draft guidelines, the draft guidelines say you need -- they recommend 400 patients enrolled in your trials at the dose and the interval you want to go to market with. That's to allow for attrition.

So you come in with over 300. We will have well over 400 patients between both trials at the 6-month dosing at the 6-month interval at the 2.7 milligram dosing. So, we're very comfortable with the safety database that we will be coming in with. And I will also remind you, we can file after 1 year, 56 weeks, but both trials will be -- have a second year, which is a safety year only, and then we will file an sNDA for the extension after the second year. So go ahead, if you had another.

Yes. Just a very quick one on filing. So, could you please remind us what could be the advantage of like filing the traditional way versus the 505(b)(2) pathway that some competitor trials like they are talking about that while the traditional one might be slightly longer, are there distinct advantages that you get there?

My understanding is that, if you are filing with a drug that's been approved already, there is a potential 2-month savings over the traditional pathway. Now as you're aware, the FDA has talked publicly recently about accelerating the pathway in various ways, and we will obviously be looking at those for our filing.

Regardless, if you have a moiety that's already been approved, but you're putting it now into a drug device combo. There's rules around what you need to file with for drug device combo. And we all have the same necessary clinical studies and CMC package that has to be delivered.

So, there's a short potential savings there. But again, we are quite confident in -- given the rapid rate of enrollment that we've had that we will be first to file and if the filing is accepted, first to approval and first to launch among all the currently studied sustained release in the marketplace or potential marketplace rather.

Our next question comes from Lisa Walter from RBC.

Maybe just on the pivotal trial progress. Should we expect any other updates beyond safety, like patient retention perhaps between now and when the pivotal trials begin to read out in mid-2026? And also, just curious if you are planning to run an open-label extension study for DURAVYU.

Thanks for the questions. The second one is easy. Yes, we will do an extension study. We're in the midst of really planning that out, and we think that will provide tremendous value for practitioners and patients to understand the long-term benefits of DURAVYU. So that is in the planning

As for pivotal trial progress, again, I do expect that we will give an update on the basic demographics of the enrolled patients. We will likely give periodic safety updates as we receive the mass safety data. And that's what we have planned at the present time.

Ramiro anything else you'd like to add about potential other masked interval additions?

No, I think you covered well. And also, we know the -- there always the potential risk of introducing bias, if you start disclosing too much in a Phase III study. So we are assessing that one.

Our next question comes from Colleen Kusy from Baird.

Congrats on all the progress. If I can go back to the rescue criteria, can you talk about how the FDA views the rescue criteria and how they would handle the evaluation of the Phase III data for those patients that got rescued? And then separately on DME, any realized details are going to be forthcoming there, but any color you can share on the feedback from the FDA? And what are some of the factors you're still considering?

Sure. So with respect to rescue criteria, the FDA, as far as I know, which only is limited to what we have been told and what we see publicly is they allow companies to apply their own standards for rescue criteria. And that's what we've done. Again, we were able to develop our rescue criteria based on real data. We did a large Phase II study, the DAVIO 2 trial, which not only informed us about efficacy of our drug, but safety as well as statistics and really gave us good data on what really should be done with respect to rescues.

DME, we were very pleased with the discussions with the agency. We are excited to start the pivotal program. And by start, I mean first patient enrolled in 2026. Technically, we've already started in the sense of preparing and manufacturing the inserts and obviously getting the clinical protocols ready. We're waiting for the written minutes. And after the written minutes in the fall, we will update publicly on what our plans are.

One of the things going back to supplements, though I might add, is that supplements are not viewed as a treatment failure in our trial. The supplement patients have sensitivity analysis that will be applied to them, and that's according to the statistics package that we've worked out with the FDA. And that's consistent with the real world. Because in the real world, if you had a patient who required anti-VEGF injections, say, every 4 weeks, and you gave them a DURAVYU, and we're safe, tolerated, effective, FDA approved with a 6-month label, yet they required 1 or 2 supplements over a year, that would be a tremendous value to the patient and the practitioner to go from 12 shots a year to 4. So, reflecting the fact that the idea of supplement because TKIs have a different MOA, supplementation in the real world is not necessarily a treatment failure. I think that's also reflected in how they will be handled in the pivotal trials.

Our next question comes from Graig Suvannavejh from Mizuho.

This is Sam on for Greg. Congrats again on the quarter and all the progress. Maybe 2 quick ones for me. First, in terms of ASRS, just curious what the feedback has been from the physician community with their review. And then also for the upcoming presentation in September with the full end of study VERONA data, what incremental data should we be expecting compared to the top line?

Thanks, Jim. We just got back from ASRS in Long Beach, and we had multiple meetings with advisory boards of various age groups and times in practice and a lot of one-on-one meetings. And I have to say, it was incredible. I mean, I was blushing. They were saying such positive things about our company and our program. They -- multiple investigators thanked us for allowing them to be in the program.

And so it really was a kind of a nice segue from our announcement to full enrollment to the incredible positive feelings we had from all aspects of the retina community, not just about the execution of the trial and the ease of enrollment and the pleasure that they had being in it, but even the doctors who weren't in the trial, starting to understand that, first of all, we're the next ones up with pivotal data in wet-AMD in about a year.

So, we are the next ones up for both studies in about a year. So, they're excited about that. They're excited about the potential of a new mechanism of action, not just another anti-VEGF that may give another week or 2 of extension, but a true extension possible for 6 months or longer with a new MOA.

So yes, it was -- is a very, very productive, and I have to say, fun ASRS, and we really are looking forward, our entire team is looking forward to further interactions with the retina community and partnering with the retina community to really help their patients. As for what's coming in September, I'm going to defer to Ramiro for that update.

Yes, Sam, thanks for the question. I don't want to disclose so much because those presentations, retina society are important. But we're going to be building more on what we have presented before in terms of BCVA, CST and treatment burden for the VERONA trial.

Our next question comes from Daniil Gataulin from Chardan.

Congrats on the progress. Just a couple of quick ones for me. With respect to LUCIA trial, what fraction of patients were U.S. versus ex U.S.? And with that experience of enrolling ex U.S. patients, how would you describe the awareness and overall interest among patients in ex U.S. compared to here in the United States?

So I don't have the exact final numbers for, but the last I saw, it was approximately 80% U.S., 20% ex U.S. I think that reflects to a large degree, the fact that things went so fast in the United States that by the time we were able to get the ex-U.S. sites up and running, we, in some cases, were near the end of the study or at the end of the study. But the interest in a sustained release, safe, effective 6-month option ex U.S. is really, really great.

As you know, in some countries, getting long-term acute care, meaning monthly or bimonthly injections for a chronic problem is difficult. So both patients and practitioners were really excited about what DURAVYU might have to deliver should we be approved.

Our next question comes from Yi Chen from H.C. Wainwright.

Could you please let us know whether there will be another Data Safety Monitoring committee meeting before the first data readout in mid-2026? And also, how should we look at the level of top line revenue in the coming quarters?

The first question about the DSMB, Ramiro, do you want to answer that?

Yes. So as a typical Phase III program, we have a DMC meeting every 6 months. So, we expect to have at least 2 or more of those before the top line results.

And the second question was about revenue? I'm sorry, you broke up a little bit.

Yes. The level of top line revenue that you expect for the coming quarters?

George, top line revenue.

Yes. So, you'll see in the Q -- our -- recall that we exited the commercial business 2 years ago, we had some follow-on revenue recognition really associated with that. It wasn't cash driven, and that was completed in Q2. And so moving forward, our revenue line will be de minimis. We still supply commercial product to our partner in China. But that -- we don't expect that to be a material number. We've really transitioned, as Jay said at the opening, to being a clinical stage company.

Our next question comes from Greg Harrison from Scotiabank.

This is Joe Thomas on for Greg. Just digging a little bit more maybe into the competitive landscape going forward and particularly the timing to market now that the competitor has announced that they won't read out their second trial until 2027. What advantage do you think that first-mover advantage in being first to market will give to DURAVYU wet AMD?

Joe, thanks for the question. Taking a step back, this is a huge market already. It's $10 billion in growing. And that if you look at drugs with a new MOA being launched into a new market, having 2 competitors actually is additive.

So, we think having other companies interested in TKIs and sustained delivery is a good thing. In saying that, the first-mover advantage is really important. And I think there's quite a bit of research around what the first mover advantage can be. But it's not just first mover. It's also ease of use and the label. We're confident that if we are approved, we will be approved with a label of every 6 months. And that flexibility to treat patients who may have recurred at 7 months or 8 months with fluid, again, at that point with your drug, I think, is going to be something that's going to be quite helpful to us.

Our safety database from the Phase II, very strong. Our safety continues in a mass fashion to match that. So, we also believe that we will come out compared to other potential competitors in the space with a probable safety advantage. So, it's not just the first mover. I think there's a whole package of reasons why we are confident that we will be the leader in drug delivery sustained release in the retina should we be approved for many years.

I am showing no further questions at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program. You may now disconnect. Everyone, have a great day.

Good afternoon. Thanks for listening. My name is Jay Duker. I'm the President and CEO of EyePoint. I'd like to thank Goldman Sachs for inviting us to present today. And we are a publicly traded company, and I will be giving some forward-looking statements. If you'd like our full legal disclaimers, I invite you to go to our website.

EyePoint is the leader in sustained-release drug delivery for retinal diseases. Our lead asset is called DURAVYU, which consists of vorolanib, a small molecule tyrosine kinase receptor inhibitor, which is best-in-class. It's patent protected. It's in our patented Durasert E sustained delivery technology, which makes the inserts fully bioerodible.

We are currently in 2 pivotal Phase III trials in wet age-related macular degeneration. The first trial is called the LUGANO trial, and we announced several weeks ago that the trial is now fully enrolled with over 400 patients randomized. The second trial is called the LUCIA trial. We announced it's 60% enrolled as of several weeks ago, and we've updated our guidance to have full enrollment in the LUCIA trial in the third quarter of this year.

In addition, we're the only TKI program to be in diabetic macular edema or DME. We had highly positive efficacy and safety data from our Phase II VERONA trial in DME. And in fact, we've had favorable safety profile across multiple indications with over 190 patients treated with DURAVU to date.

Our cash looks great. We currently have $318 million at the end of the first quarter, which gives us a runway into 2027, approximately a year post data from the Phase III trials.

This is our pipeline. Again, we are in Phase III and 2 wet AMD trials, LUGANO fully enrolled, LUCIA by 3Q. We have positive Phase II DME data, and we will be updating our DME plan later in the year for pivotal trial. And in addition, we have EYP-2301, which is the small molecule called razuprotafib that we've been able to put into sustained release. This is a TIE-2 agonist, and we will be advancing it for serious retinal diseases.

We have some pretty good treatments for wet age-related macular degeneration. They're safe and effective, but they all lack one thing, which is durability. And there's significant evidence that we need more durability in wet AMD. Many patients are chronically undertreated. And in the long term, many patients lose vision because they are undertreated.

The short-acting current anti-VEGFs put a great burden on patients, on practitioners, on families and on society, and missed visits can result in permanent visual loss. There is evidence that even one missed visit in scheduled therapy could result in significant visual loss. The fact that we have an aging population with increased lifespan only means there's going to be more and more patients who get wet age-related macular degeneration and require long-term therapy.

Diabetic macular edema is another area for which we have good treatments, anti-VEGFs that are safe and effective. Durability is needed. Diabetic macular edema typically affects working age people who have multiple concurrent clinical problems, have to go to multiple doctor visits and the significant burden of intravitreal injections, especially in the first year means that patients can be very noncompliant in this disease.

DME is prevalent. About 1/4 of the patients will develop it. Currently, the market is about $3 billion. And again, up to 51% have delayed or missed visits, resulting in significant visual loss. So our solution is DURAVU. DURAVU, again, is a small molecule tyrosine kinase inhibitor that is in our patented delivery system that we call Durasert E, E for erodible.

The Durasert delivery system has already been in 4 FDA-approved products and a non-erodible form. Durasert E is -- each insert is tiny. It's about 15,000 to the vitreous cavity, and it's delivered in the retina specialist office with a standard intravitreal injection. Durasert E provides continuous dosing, what we refer to as zero-order kinetics. Zero-order kinetics means after initial burst of the drug, you get a steady-state release for the lifetime of the insert.

In humans, we believe the inserts will last a minimum of 6 months in all patients, and the majority of patients should have the drug depleted by month 9. These are solid injectable inserts. They're in a bioerodible matrix, and they are designed to erode drug fully before the matrix goes away.

What you don't want is your matrix to go away before the drug is fully eluded because you will then have free drug particles in the eye, which can be a problem. We have favorable safety profile across multiple indications. And again, this is a fully erodable matrix.

Vorolanib is a small molecule tyrosine kinase inhibitor, selectively inhibits all VEGF signaling because it inhibits all VEGF receptors. In addition, it inhibits PDGF, which should lead to an inhibition of fibrosis.

In the long term, there are 3 reasons why wet AMD patients lose vision. The first is noncompliance. The second is fibrosis. And our drug should tackle both of those problems. Durasert E, again, 15,000 of the vitreous cavity for each insert, but our scientists have been able to manufacture this in a way that it is now 94% drug, only 6% matrix.

We have shown in animals and now in humans looking at our diabetic macular edema data that we have no delay in the onset of our drug release. In animals, we've shown the drug reaches the choroid within hours and within a day is at therapeutic levels. The zero-order kinetics results in no fluctuations, which should mean no fluctuations in control of the fluid, which is important for long-term visual acuity. We have no free floating drug particles in the eye.

And interestingly, we don't need cold storage. We can be shipped and stored at room temperature, which is a real advantage when you think about how big the freezers that retina specialists have to have with all the current FDA-approved products. Also, very important, we have no PEG. PEG has been implicated as the cause of potential vasculitis in sensitive patients. And we know -- we don't have any PLGA. PLGA releases into an acidic environment and has the potential to cause corneal toxicity.

We've completed 4 studies so far, the DAVIO Phase I wet AMD trial, the DAVIO 2 Phase II wet AMD trial, PAVIA NPDR trial and VERONA Phase II DME trial, a total of 191 patients treated with our drug with no safety concerns. We've had no DURAVYU-related ocular or systemic SAEs reported to date. There has been good to excellent efficacy shown through these 4 trials.

I'm now going to talk a little bit about our exciting wet AMD program, the LUGANO and LUCIA trials. These trials are designed as a noninferiority primary endpoint. This is an established approval FDA pathway. The last 4 wet AMD approvals have been with a noninferiority design. We had a non-inferiority robust Phase II trial, which showed excellent results and our Phase III program was modeled after that.

We've had proactive FDA interaction, both at a Type C meeting in 2022 about our pivotal program and again, at an end of Phase II meeting in April 2024 with agreement with the FDA on the trial design and written alignment on our masking and our non-inferiority margin of minus 4.5 letters.

This is also what we refer to as a [ clinical ] trial design. Doctors are used to the on-label 2-milligram EYLEA control arm. They know how it's going to behave in a drug against it. They will know how to use this in the real world.

To review the DAVIO 2 Phase II wet AMD results, we had 2 doses of our drug, 2 milligrams and 3 milligrams versus an on-label EYLEA 2-milligram control, and there was essentially no change in visual acuity at the primary endpoint. The 2-milligram arm was minus 0.3 letters worse than EYLEA. The 3-milligram arm was minus 0.4 letters worse. When you did this as a p-value, the p-value for these being identical to control was 0.0009.

So we had essentially the same control of vision that on-label EYLEA had. I've emphasized safety already, but the reduction in treatment burden was about 80%, depending on how you measured it. Reduction in treatment burden can refer to a retrospective look back on how many injections did these patients receive leading into the trial. And we had about a 90% reduction in treatment burden looking at this way versus how many shots withing the trial did the patients get after the load. And we had about an 80% reduction looking at it that way.

And this was a tough to treat group in our Phase II. They were previously treated patients who on average had about 10 injections a year normalized leading into the trial. In the United States, on average, patients receive about 6 injections a year, so this truly was a needy VEGF-mediated disease patient population. 2/3 of the eyes made it about 6 months after our drug was inserted without any supplement and about 50%, they did a full year.

We had excellent anatomic control. Anatomy is measured on optical coherence tomography or OCT with a normal foveal thickness of about 300 microns. Anything above 325 is considered to be abnormally thick. You can see from this slide that the anatomic control was less than one standard deviation of the test.

So this went on to inform our Phase III trial design, which you can see on this slide. The Phase III trial design consists of 2 arms: DURAVYU 2.7 milligrams, which is our higher payload insert with 94% drug payload against on-label aflibercept control. All patients get randomized on day 1. They receive aflibercept at day 1, week 4, week 8. 30 minutes later, then they either receive their first dose of DURAVYU or they receive a sham. Patients come in monthly and are evaluated monthly.

Every other month, the DURAVYU arm gets a sham, the aflibercept arm gets another aflibercept. And then at week 32, a second injection of DURAVYU is given. We are hoping for a label of every 6 months. This is a 2-year trial, but we expect to submit the NDA at the end of 1 year. Again, the primary endpoint is noninferiority change in visual acuity between the DURAVYU arm and the control arm with a blend of week 52 at week 56.

LUGANO is fully enrolled. LUCIA should be fully enrolled in 3Q of this year. A couple of announcements to make about this as well. We're really proud to announce that the EMA has approved our protocol. So we now have approval of the 2 largest regulatory agencies in the world. Some of you may be aware that the EMA barrier to approval for clinical trials is somewhat higher than the FDA. And that also leads us to be optimistic that should our trials prove to be positive that we could get approval in Europe.

We have now the first European site in the Czech Republic up and running and have now enrolled the first OUS patients in the LUCIA trial. This is a time line for the trials. And again, starting in January of this year, and you can see how rapidly we were able to enroll LUGANO. Again, we enrolled over 400 patients in about 7 months. It is, we believe, the fastest enrolling wet AMD trial recorded to date.

LUCIA is started several months behind, but is enrolling at approximately the same rate. We then expect top line LUGANO data in mid-2026 top line, LUCIA data several months later, but they are identical trials. And if we are -- had a positive top line in safety at LUGANO, we have every reason to believe LUCIA will have a similar result.

I'd now like to talk a little bit about diabetic macular edema. DME is also a prevalent problem worldwide. We did a Phase II VERONA trial in DME. The attempt here, of course, is to reduce the treatment and visit burden in diabetics without harming the visual acuity outcome.

And you can see from this slide with the 4 approved products, how often the patients would need to come in for injections and at the bottom, what we hope to accomplish with DURAVYU with every 6-month dosing.

The VERONA trial enrolled only active DME patients. They had to have decreased vision and they had to have significant fluid to be enrolled in the trial. So this is the first trial, which we enrolled patients that 100% had wet maculus.

On day 1, the patients received aflibercept and then 30 minutes later, they either received 1.3 milligrams of DURAVYU or 2.7 milligrams of DURAVYU or they received just sham. The primary outcome of this study was not visual acuity. The primary outcome was time to first rescue. And so there were no other mandated injections in this trial after day 1, but the patients came in monthly and they could be subjected to supplemental injections if they met supplemental criteria.

This is the top line result of the VERONA trial. The high dose, the 2.7 milligram dose, which is the dose we're using in the Phase III and our presumed go-to-market dose showed that the primary endpoint was achieved, extended time to first supplement versus the aflibercept control. We had early improvement in both best corrected visual acuity and anatomy measured by central subfield thickness on OCT with the improvement of 7 letters at the end of the trial and minus 76 microns dryer in CST. And again, safety looked very good, no SAEs reported due to the drug.

This is the curve of visual acuity. And I'm only showing the first part of the curve here because no patients received a supplement before week 12. So this is directly head-to-head EYLEA versus DURAVYU. And you can see at week 12, the blue line, which is the high-dose DURAVYU 2.7 milligrams was significantly better than EYLEA.

But I'd also like to point out week 4. Week 4 is directly head-to-head DURAVYU against a single EYLEA in a wet population. And look at the improvement in visual acuity and drying that occurred as early as week 4. And this was sustained for most patients throughout the study.

So if you're a patient and you have a decreased vision in a wet macular due to DME, would you rather get better at 4 weeks? Would you rather get better in 6 months? I think most of us would pick 4 weeks. So this is an early and sustained effect in visual acuity through the length of the study. At the end of the study, all 3 arms ended up with the same visual acuity, which is fine because in the pivotal trial, we're going to likely do a non-inferiority. We don't have to be better than EYLEA. We just can't be significantly worse.

Within this trial, however, there was a single outlier. And if you go back and look at the blue line again and look between week 20 and week 24, notice how the visual acuity drops. That drop was a single patient who lost 20 letters, and they were late coming in. That week 24 visit should have been a week 20 visit. And by the way, they did get supplemented at week 24 and their vision came back.

But if you take that patient out of the equation and just look at the rest of the patients in the high dose, the high dose gained 10 letters, significantly better than EYLEA. And this is the anatomy. And once again, what's powerful about this is the anatomy and the acuity, the structure and the function match perfectly. The visual acuity improved in 4 weeks and the anatomy improved in 4 weeks. That tells you it's real.

And this is again what retina specialists look for. They look for the improvement in anatomy because we know that the visual acuity can lag sometimes in this disease, especially when treated with anti-VEGFs, it can take many months for the vision to improve. But with a high dose, we had early and sustained improvement in both the vision and the anatomy. And that continued in the high dose and the low dose as well throughout the study with 75-micron improvement versus only a 43-micron improvement in the EYLEA arm.

We then went on to do a subgroup analysis and said, let's just look at the eyes that were unsupplemented. They purely got our drug or they purely got a shot of EYLEA. Let's see how they did. The top is the visual acuity. And again, the blue line is 2.7 milligrams DURAVYU only after that single shot with EYLEA at day 1. Notice that the improvement in vision is 7 letters at week 4 and about 10 letters at week 8. It's very fast vision improvement, and it's sustained.

The line is flat through the rest of the trial. What this tells you is when this drug works in DME alone, it works really well. These patients weren't gaining fluid or losing vision at the end of the trial. And again, look, the second graph at the bottom is the CST, early improvement of 120 microns. Now these eyes started at 420 microns. 420 minus 120 is 300 microns on average, they were normal within a month after injection.

And it was sustained throughout the study. So again, these are about 70% of the patients were rescue-free in the high dose and the results were really, really fabulous.

Now I want to show a couple of cases. This first case is from the 2.7 milligram arm, and they did not get supplemented. This is purely with our drug. On the top left is the screening, and you can see this eye has swelling. If you've never seen an OCT before. These black areas in here, that's the fluid within the retina. Best corrected visual acuity is 50 letters. That's not great. 20/20 is 85 letters.

And you can see between screening and day 1, the eye got worse, dropped 4 more letters and got more fluid. What did they ever receive before? They had 2 EYLEA injections 12 months and 10 months before enrollment. They had Vabysmo 7 months before enrollment. So Vabysmo probably were off by them, but you can see this active disease.

And how did they do? Well, take a look. At month 1, that is a normal foveal contour, normal macula and improved about 20 letters at month 1 and stayed improved through month 6. Now you could argue, well, maybe that EYLEA did the job for that month 1. Well, maybe except that the EYLEA would have worn off by month 6. So that shows that immediate improvement in good longevity of our drug in this DME patient.

The next case, I think, is even more impressive. If you look at the top right here, you can see this patient got Avastin 9 months before enrollment and then basically got monthly Vabysmo. So if you think the retina specialist has given monthly Vabysmo, why are they given a monthly because they feel like they need to. Otherwise, they would have extended the interval here.

So how did they look 2 months out of the last Vabysmo? They had a cyst of fluid, they had 72 letters. And then several weeks later after screening when they actually got enrolled, they have even more fluid. Now at month 1, they had less fluid, not a lot less, still had some activity. You might say, okay, that was the EYLEA effect. Maybe. But at month 4, there are almost no normal foveal contour and look at the improvement of about 15 letters. That's 3 lines on the eye chart. And look at month 6, no fluid, no normal foveal contour, 80 letters.

So here is 6 months after our drug went in, take a look at what they were 2 to 3 months after Vabysmo. I think you argue in this eye, our drug was better than Vabysmo for DME.

So the summary of VERONA is we met the primary endpoint for both doses, immediately clinically meaningful results without a full load of aflibercept, just one. We got that significant improvement, and it lasted in the high dose through the length of the study. The subgroup analysis showed that the supplement free eyes were what was really driving the excellent result and continued favorable safety and tolerability.

We have an end of Phase II meeting scheduled with the FDA for next month. We will update investors and analysts at the -- likely the end of the summer, early fall and what the plan is for DME. But at present, we intend to start the DME pivotal trial or trials in 2026.

We're very proud of our new manufacturing facility. Our planning all along has been to grow EyePoint as a successful pharmaceutical company, not just thinking about the next clinical trial success, but long-term success and long-term drug development. We realized several years ago that our Watertown facility was not going to be adequate for commercial. And we sought out a new facility. We looked all over the United States, ended up with a site about 45 minutes west of Watertown in Central Massachusetts in a small town called Northbridge.

We built a 41,000 square foot facility with 8 state-of-the-art clean rooms that opened in October. This is built to U.S. FDA and EMA standards. We actually had the FDA involved in some of the planning. So we had their sign-off on the plans. And we are in the midst of doing DURAVYU registration batches to support the future NDA filing. We would expect that this facility could fully support, if successful, the commercial activity for DURAVYU, both in the United States and ex U.S. We believe that we can make over 1 million inserts a year potentially in this center.

So this has been a really, I think, terrific story of execution by EyePoint. I do like to brag that the first patient ever treated with DURAVYU was treated in January of 2021. And here we are about 4.5 years later, fully enrolled in one pivotal trial with another one about to fully enroll a brand-new manufacturing facility and really terrific efficacy and safety data for our drug.

The green check marks show you some of the things we've done in the last year with upcoming events, the end of Phase II meeting for DME, full enrollment for the LUCIA trial we expect in 3Q and top line data for LUGANO mid-2026.

Thank you again for the invitation. I appreciate you all listening. And if there are any questions, happy to answer them.