Okay, good morning, everyone. Welcome to Guggenheim Emerging Biotech Emerging Outlook Biotech Summit 2026. Our next presenting company is EyePoint. From the company, we have their Chief Financial Officer, George Elston. My name is Yatin Suneja. I will be moderating the discussion here with George. George, why don't you make some opening comments? Obviously, a pivotal year for the company, right? Two studies fully enrolled, and they're going to start reading out relatively soon, and you have another phase III program that you are taking on on the DME side. So why don't you orient our investor when the data are coming, and then I have prepared a few questions for you that I'm going to ask. Sure, great. Yatin, thank you for having us here. EyePoint's very happy to attend this conference. I think as you say, 2026 is setting up as a really remarkable year for EyePoint. On the heels of 2025, which was another remarkable year for EyePoint, and maybe to bring everyone to today, we enrolled 2 wet AMD trials last year, phase trials, over 450 patients each. So in each trial, we enrolled in about seven months, which was really record time in wet AMD. Over 900 patients in those trials. Really great enthusiasm, you know, taking that into this year. We've given safety updates from the DSMC over time, and, you know, so far, so good on those trials. We're not surprised. We did a real phase II, which informed phase III. It allowed doctors to speak to their patients and get those trials enrolled. You know, right now, it's all about trial integrity, and so our clinical team is really spending time there. You know, things couldn't be going better at EyePoint. You know, part two of the equation, which is DME, which is the second largest multi-billion-dollar opportunity in retina. We had really robust data in VERONA trial last year in DME, where we had immediate separation between our drug and EYLEA at week four, and we essentially maintained vision and kept fluid down for 24 weeks. So that trial, we have initiated that at the end of last year. We will be announcing first patients dosing this quarter. That guidance still remains, and we're very excited about that. Those are 240 patient trials each. We expect those to enroll pretty quickly. There's a lot of enthusiasm out there for that. Got it. Then part two is our manufacturing. As we think about, you know, our wet AMD trial, the first trial, LUGANO, will read out mid-year. Mm-hmm. - and LUCIA a few months behind, which really sets in motion, obviously, upon success, that we'll be aggressively moving to file our NDA. The clinical data is certainly important, but so is CMC, and we've got our Northbridge, Massachusetts manufacturing facility up and running. That team is working essentially around the clock, so that way, we are in a great position to meet that expectation from FDA as well. Got it. Thank you for that. So let's just start with high level. What is DURAVYU? What is the concept here? What are you trying? What have you actually generated, and what are you trying to achieve? Yeah, so DURAVYU, which is our lead asset, it's the small molecule tyrosine kinase inhibitor, vorolanib, in our Durasert E technology. And what Durasert E does is it allows us to essentially manufacture a solid insert, which is injected into the vitreous of the eye. It's an intravitreal injection, and the beauty of this technology is it allows us to control drug release over time. And so for DURAVYU, in both wet AMD and DME, we expect it to be at least a six-month drug, right? And so we are going with every six-month dosing. We want that on the label. And, the beauty of the Durasert technology, it's a fully bio-erodible insert. It's each insert is about 94% drug, 6% matrix, and it's for at least six-month dosing in humans. And, the redosing in both trials will be every six months. Mm-hmm. What's nice about vorolanib and the TKIs as a class in wet AMD, if you look at the wet AMD space over the last 15+ years, it's been treated by a single MOA, which are these large molecule biologics. There's really been no second mechanism of action, no new treatment modality for that disease. What we see as an exciting opportunity for DURAVYU and wet AMD, if you think about the space historically, every new drug says: "Use us, we last longer than the other guys. Stop using them." Our story is going to be very different. Our narrative is: Use DURAVYU. You're going to have a new MOA. If you need to supplement with an anti-VEGF, VEGF biologic, go right ahead. Go right ahead. Use both. Yeah. Yeah, Yeah, yeah. It's because the current standard of care is, you know, still is every two months or every three months at best, right? Yeah. Maybe four, but so you're really trying to move it to six or maybe longer. Okay, now, these two studies, the LUGANO study, could you, because obviously, that has been the key focus for our investors. What specifically are you looking for, or what specifically are the expectation for both the primary endpoint and the secondary endpoints? Yeah, so we at EyePoint do drug development, right? And if you look at every drug since Lucentis, they've been approved on the non-inferiority pathway with FDA. Yeah. We are pursuing that with our clinical program, with our pivotal trials. We are looking for non-inferiority versus aflibercept on-label, and that's critical to do a non-inferiority trial. That non-inferiority margin is - 4.5 L. But your control group has to behave like the groups that were the non-inferiority margin was established, and that's why we are doing on-label aflibercept. If you look at our phase II, we were actually statistically non-inferior in a very tough-to-treat population, and in the supplement-free eyes, DURAVYU actually did better. We do not need to beat EYLEA in the phase III, we simply need to be non-inferior, and we were well informed by a phase II for that. Secondary endpoints are obviously safety. Yeah. In ophthalmology, safety is critical. We've seen drugs in the past really stumble because of safety issues, and we are very proud of our safety profile through phase II. We've had 190 patients through four different trials going into our phase III with no safety signals, no DURAVYU-related ocular or systemic SAEs. So safety is obviously a key secondary endpoint, and then we'll be looking at reduction in treatment burden and time to first supplement. Got it. So maybe just first on the non-inferiority. I understand the margins are minus or the number is - 4.5 L sort of margin, but in the DAVIO study, you were actually close to being superior or similar, right? So, like, what are you hearing from physician? Like, what do they want? Is there a one-letter, two-letter, or are they okay with four letters? So I think most physicians want to know who do I use it in and how do I get paid, right? Yeah. So if actually, if you use high-dose EYLEA as a reference, high-dose EYLEA was 1.4 L worse than regularly- Yes ... in their phase III. Yes. But it got approved. Yeah, going back to our phase II in a very tough-to-treat population, you know, we were equivalent. Yeah. Our trial is not powered for superiority. Sure. It's powered for non-inferiority, and, you know, that's how we're gonna be looking at it. We will certainly be allowed to. So if we hit non-inferiority, we will be allowed to test for superiority, and that's something that's, it's in the plans to do as well. The goal is to come as close as possible to EYLEA, basically. The goal is- Basically ... to be statistically non-inferior. Non-inferior, yeah. That's the hurdle for FDA approval. Yeah. I think that's an important point because how... You know, we get the question often: How will this be used in practice? Well, you know, you do trials based on regulatory requirements, and that's the way we built this study. Got it. I think beyond that, we'll do additional trials- Yeah ... to support the marketplace. Yeah. When we look at either the treatment burden or reduction in treatment burden or rescue-free rate, what are we looking at? What are some ballpark numbers that you sort of tell investor that, "Hello, this would be meaningful," or you hear from KOL, this is meaningful? Well, if you go back to DAVIO 2, you know, we were, we had a 80%+ reduction in treatment burden in those trials. It's gonna be a little bit different in the phase III because there is redosing. Yeah. So the stats are gonna be... The number is gonna be lower, but we need to show a reduction in treatment burden. You know, one thing we're looking at is we will test for superiority and reduction in treatment burden as well. You know, I think doctors, you know, there's a whole range, but I think what's unique about our program is, you know, a supplement's not necessarily a bad thing. Yeah. If you take a patient from six injections a year to four- Mm ... that's a win. Mm-hmm. We'll certainly be looking at that closely. Again, going back to the phase II, we took two-thirds of patients six months on just our drug with a pretty generous retreatment criteria. Got it. What about rescue-free rate? Because that's also another area where we all focus on. Sure. So that, you know, similar to the Phase II, it was a, We had two-thirds Mm. Two-thirds of patients went six months with just our drug. Actually, 50% went a full year. So that, that's something that we're looking at, and obviously, that's gonna be critical to the ultimate results of the trial. But remember, you know, we built the trial on the phase III. Yeah. So, and an important point of that is if you look at the supplementation criteria, and we learned a lot from phase II. Phase II, I think we had five different supplement criteria, including investigator discretion. Mm. When our clinical team went back and looked at that, 20% of the supplements met no criteria. The investigator discretion met no criteria. So there was. And a lot of the supplements, you know, that were done really had no impact on vision, and so we made meaningful changes for that in phase III to essentially one, and that is a 5 L loss with 75 microns of fluid due to wet AMD. And that allows us to protect that lower bound of the non-inferiority margin. There's no investigator discretion. There is a supplement allowed for hemorrhage, but that has to be adjudicated through a KOL review board. And we think as a result of that, as well as including newly diagnosed patients, that we should do better. We hope to do better in the phase III on supplementation. Got it. So you have better, let's say, these rescue criteria. Can you just talk a little bit about the patient population, why they are different than, DAVIO 2 study? What happens or, like, how does including naive patient and what proportion there might be, helps you with this study? Yeah, it's, you know, no, no surprise when you do a phase II trial- Yeah ... you're not getting the most behaved patients, right? If you're a doctor and you have a patient that's coming in every three months or every four months, you're not gonna enroll them in a trial where they have to come in monthly, right? And so we didn't get any of those patients in the phase II. What we got were high, high-need patients. And if you go back and look at the details, those patients, on average, were getting 10 injections a year. In the U.S., you get about six, and we did really well in that population. Mm. So as we looked at the phase III, we really wanted to solve for two things. Number one is we certainly wanted to reduce the amount of supplementation, but we wanted a wider label, so we moved to include newly diagnosed patients. Everyone still gets that EYLEA load- Yeah ... and so by the time they get our drug, they're technically not... They're, they're experienced, but that's the definition. So it's 75% newly diagnosed, 25% previously treated. We got none of those every three-month, every four-month patients in the phase II. Mm. We think we'll do really well with those patients. In fact, we looked at a subset when we went back and looked at DAVIO 2, we called them, I think pseudo-naive, and they did really well with our drug. And so we expect it will help a broader label- Mm. and it will help certainly reduce the supplementation rate over the twelve-month endpoint. Got it. So both the studies enrolled really fast, right? In about seven-month timeframe. Could you just talk about what was driving that? And given such a rapid enrollment, how did you ensure the quality of the patients, the site, and you really got the patient that you really wanted? Yes. So a lot of credit to our clinical team, and worked very closely with our CRO. We were in, you know, we were in about 200 sites worldwide. You know, it's drug development. Mm. We did a Phase II. You know, when you go into a site, and you have really robust safety and efficacy data that you can point to for enrollment, and our trial also allows everyone gets treated. Yeah. So you're at least getting standard of care. And so there's supplemental criteria, so when you're a physician talking to a patient, there's a great opportunity to say, "Listen, you're going to get standard of care at a minimum, and there's a real opportunity to actually get fewer injections." That was really well received. And you know, there's a lot of other things that we learned in the phase II that we applied in the phase III, so I will call them trade secrets because it allowed us to really help in recruitment. But you know, coming back to the population, you know, we had strict entry criteria, and we've got a really smart, robust clinical team that works closely with our CRO, and so as patients were enrolled, you know, they had to meet that entry criteria. You know, our Chief Medical Officer, he's done global phase IIIs before. He knows in, in retina, he knows where the good sites are, and so it shouldn't be any surprise- Got it. - that we recruited so quickly. Got it. Could you touch on the safety? Because, again, in ophthalmology, safety is something that everybody's really particularly focuses on. What have you... I mean, obviously, we have seen the data on the 190 patient, but at least on these, the two studies, what is DSMB looking at? What are they telling you? What about re-injection, right? Like, what risk does it introduce, and what do you see? So, a couple of things. Remember, we've done redosing in animals, and going into the phase III FDA and all that data, we've seen no dose-limiting tox, number of inserts, so our, our safety profile in humans and in animals remains really exceptional. What the DMC, DSMC sees, they see all the unmasked data- Yeah ... for safety. So they met in May, and I think they met in November. We gave that most recent update. They recommended no changes to the protocol and continue, you know, as you've seen. And we've made the statement that, you know, we've seen no differences in the unmasked data that's any different than what we've seen in prior trials. So just from a kind of a simple math perspective, there's roughly 900 patients in both between both trials. Around 450 of them received DURAVYU, 2.7 mg. Everyone's received their first dose. Probably 70%-80% have now received two doses. And all is great, right? I mean, if there was an issue, we would have heard about it. We're, we at EyePoint, we're not surprised. This is Durasert technology. In prior versions, it's been in thousands of eyes. We know that vorolanib got a great safety profile in the eye as well, so we're feeling really good about our safety. We have no safety signals to date with DURAVYU, and- You're saying no? We have no- You're not saying not new. We have no safety signals for DURAVYU, and we've seen no systemic or ocular SAEs with DURAVYU, so we feel really good about our safety. Very good. What about, you know, obviously, you're giving insert every two, or sorry, every six months. Maybe in real-life practice, might be nine months, we don't know. At steady state, how many insert are going to be there? How should we think about the two-year readout? Any concern around buildup? Yeah, so this question comes up frequently, and it's a hypothetical question. Yep. So if you think about these inserts, each insert is 1/5,000th of the vitreous, approximately. Each is 94% drug, and we know from our animal trials that the drug is gone in about nine months, so there is, you know, less than 6% remaining of a very, very small insert. So the math becomes very simple, and, you know, we don't... And remember, these are heavier than water. They drop to the bottom of the vitreous. They're very hard to see, and they become translucent as they shrink. And so it's all anecdotal, but we've had... You know, we published our AE tables from phase 2. Mm-hmm. We have no difference than a IVT injection, and you know, it's you know, so far so good. I think, you know, remember, this is the Durasert technology. The prior versions were non-erodible. They had a polyimide shell that remains in the eye, but it's the same matrix. Mm-hmm. And so there's, we expect, you know, based on what we've seen in animals, is that remaining matrix to erode over subsequent months, you know, at the end. Got it. Okay, that is helpful. In terms of, like, just from the readout perspective... Are Are you going to announce—So the first study will be announced obviously first, but what about the BL—oh, sorry, NDA? What is the safety requirement? How much safety you need before you can submit it? So, FDA is very clear with us and everyone else, so you need 300 evaluable patients at your go-to-market dose and your go-to-market interval, and we expect to have that from LUGANO-LUCIA. And it's 450 patients, and even with some expected patient fallout due to time, you know, we will be well above that number. So LUGANO will read out, call it, you know, sometime this summer. We announced full enrollment at the end of May last year. It's a 56-week endpoint. We will need time to block the database, so, you know, sometime this summer will be LUGANO, LUCIA will be several months later. The nice thing about this trial design is they're identical trials. Yeah. So LUGANO is, should inform LUCIA, and as we think about building our NDA, we will use LUGANO as the template and simply drop the LUCIA data in, and we think that's going to help us accelerate that filing. You just need 56-week data? You don't- Right. So we're blending 52, 56. Yeah. That's the endpoint. Yeah. Yeah, and assuming patients come back on time for their last visit. When would you need two years' data? Do you need two years' data from a filing? So these are two-year trials. However, the endpoint is- Yeah ... 56 because that's where the non-inferiority margin is. Yeah. So our plan is to submit the NDA with the one-year safety and efficacy, and then do an sNDA with the two-year safety. DURAVYU is redosed every six months for two years, and that's important because we want, you have the interval on your label, you'll, you will get unlimited dosing. We think that will be a significant competitive advantage for us. Got it. One commercial question before I go to DME. When we poll, KOLs, we get a number which is 25%-40%, and that number has been consistent, that 25%-40% of wet AMD patient would be candidate for a concept like this, right? What do you hear from like, what is your check suggesting? Is that in the ballpark, or you, you get different numbers? Yeah, I think that's very consistent, and there's some assumptions on there on sharing the market and... But, you know, wet AMD is a $12 billion market, so 40% is a real product, right? And if you look at the success of VABYSMO in that space, in, you know, two and a half years, it's a $4 billion drug. And their promise is, if you look at the published data, they last, you know, days or weeks longer, not- Yeah ... not months. So we think that's a really interesting analog for us. But remember, that's not our competition. We expect to work with them, not instead of them. And so, you know, 20%-40% is, you know, very pretty consistent. I think we're also well aware of KOL standing on the podium saying they'll use these extended TKIs in 80% or 100% of their patients, which is, you know, very, very meaningful. The truth's probably somewhere in between, and I think it's going to come down to data and launch, and I think we've been well ahead of the curve on this as we- Yeah ... built our Northbridge facility to prepare for that U.S. commercial launch. How big of a commercial build-out would that be required to launch it? Why would you be preparing to launch it on your own? Yeah. So we've been pretty consistent about this. So, we plan on launching DURAVYU in the United States by ourselves. I think the nice thing about retina in the United States is you can address it with about 70 reps and a slightly larger commercial infrastructure. We have had commercial products before. We've established- we have a very functional pre-commercial team and our medical affairs team, and we've built a lot of relationships in that community already. And so it, it's not a heavy lift to launch a drug in retina. We are certainly aware that there are two well-funded, well-established players- Mm-hmm ... but we're coming at this from a slightly different angle. Got it. Got it. Okay, and you believe in two studies that are required? Yeah. Or is there an option for one study? So there's a lot of noise about that, obviously. We're doing two trials. They're gonna read out this year, so it's sort of a moot point from our perspective. It's gonna be a robust data set, and it's consistent with FDA requirements, going into this, you know, we've heard Dr. Macari speak about single trial. Yeah. Actually, the FDA has single trial rules already. Yeah. And if that is ultimately the case, pardon me, it's fine, and there's a pathway, but we're gonna be, you know, very... You know, we'll, we're gonna be-- we still expect to be first to file, first to market- Got it ... in this extended space. Got it. Then quickly in the next, like, two minutes that we have on the DME side, where are we on the two DME studies that you are planning to initiate, COMO and CAPRI? Are there differences? Actually, how big is the DME market in your view, or what are your estimates around that, and then what are the timelines for it? Yeah. So, I mentioned our phase 2 DME data. We think we've got a real opportunity here in DME. This is a different population than wet AMD. It's working age. They're not really able to come in monthly, which is the current standard of care. And what we saw in our phase II is we had this robust separation at week four, and so we're hoping to demonstrate that in the phase II as well. Mm-hmm. So, DME program, COMO and CAPRI trials, they're each 240 patient trials. We've initiated them along with our CRO in the fourth quarter. We'll be updating the street, and our guidance remains that first patients will be dosed this quarter. We expect it to take about six months to enroll, with data potentially by the end of 2027. Oh, wow! Very good. How big is the market? So in the U.S., it's about a $3 billion market, dominated by the anti-VEGFs. There are other products there, like steroids. What we really like about DURAVYU for this indication is compliance, right? Mm-hmm. So we know we have the separation. We know that DURAVYU, and we talked about this last fall, in addition to being an anti-VEGF, we actually block IL-6 through JAK1, which is a key inflammatory pathway in DME. We hope to show that in the phase III trial. And if you're a doctor and your patient's in the chair, and you know they may or may not come back next month, and you have the ability to give them a six-month insert, we think we've got a real opportunity, if successful, to grow that market. Got it. Got it. Final question. How is the financial health? What is the capital spend and requirement going forward? We ended 2025 with $300 million of cash, and our cash guidance is unchanged. It's into Q4 2027, that fully funds our ongoing pivotal programs in both wet AMD and DME, along with our manufacturing scale-up and NDA submission. We are in a great place. We expect to have well over a year of cash when we read out the LUGANO trial later this year. Excellent, George. Thank you so much. Thank you. Appreciate it. Thank you. Thank you very much.