Hi, I think we are live now. Good afternoon, everyone. My name is Yatin Suneja. I am one of the biotech analysts here at Guggenheim. Welcome to our inaugural Healthcare Innovation Conference. Our next presenting company is EyePoint. From the company, we have a few executives here. With me on the podium is Jay Duker, who is President and Chief Executive Officer. I also have George Elston, who is the Chief Financial Officer here with me. Jay, why don't you maybe make some opening comments, spend five minutes, and then we'll go into the Q&A. Sure, thank you, Yatin, and thanks for inviting us. Thanks, everybody, for coming. EyePoint, at its heart, is a drug delivery company to the back of the eye. Our lead asset is called DURAVYU. DURAVYU is a combination of Vorolanib, which is a small molecule tyrosine kinase inhibitor, with activity against all the VEGF receptors. It's in our patented Durasert E technology, which allows it to be sustained release with zero order kinetics in the eye for up to nine months. The E is for erodible. It's a completely erodible form of our sustained release product. We have had four FDA-approved sustained release products prior, which were in a non-erodible form. DURAVYU has just started phase III trial in wet age-related macular degeneration, and we are in phase II in diabetic macular edema. Just recently, being an open label trial, announced interim data in DME, which was quite good. Yeah. Yeah. So let's just start with the VERONA study in DME. What was the relevance of that study? How important were the readouts, some key findings, and any implication to the wet AMD side? Sure. So the VERONA trial enrolled previously treated diabetic macular edema patients. And unlike our wet AMD trials, VERONA enrolled active patients that had wet maculas. They had to have at least 325 microns of fluid, and in fact, most on average had 400 microns, at enrollment. They had to have decreased vision. So this was the first trial where we tested our drug with all active patients. DME, of course, is a very prevalent problem, and while the market is approximately 40% of the wet AMD market, it is smaller. The need for durable therapies is even greater in DME because of the nature of the population. It's a younger population who have multiple medical problems. They really don't like going to the doctor, and they really miss visits, which then hurts their final visual outcome. We enrolled patients and they were randomized to either 2.7 mg of our drug versus 1.3 mg of our drug versus an Eylea control. This is the first opportunity that we tested our new higher payload insert in humans. It passed with flying colors, by the way, with no safety concerns at all. Of course, the efficacy data, which we'll get into, was quite good. The study was designed as what I refer to as a PRN study, which means at the time of first day of enrollment, everybody got a shot of Eylea, and 30 minutes later, they either got their assigned drug or they got sham. They came in monthly with no further assigned injections, but all the eyes were open and available to get a supplement if they met certain criteria. That criteria, in fact, there were four parts to the criteria, which were exactly the same as the criteria we used in the wet AMD phase II, the DAVIO 2 trial. But we added a fifth criteria, which is if the eyes, starting at week 12, didn't have a 10% reduction or more in their CST, they got supplemented. And the reason we put that in was for patient safety and to do what's right for the patient. These patients all entered with decreased vision and a lot of fluid, and we didn't think it was right to watch an active patient for six months without therapy. Okay. Okay. How relevant was the Eylea arm there? Certainly in the short term, one would argue was highly relevant because as we get into the data, I think you may notice that, we had a clear separation from Eylea at week four. So that meant our drug alone outperformed the Eylea arm. Yeah. Even at week four, which showed, first of all, several things. Our drug is immediately bioavailable, which we've said all along. Our drug does not require a full load of Eylea to work. Correct. We've said that all along, and we improved nine letters at four weeks in our top dose, which is really a very, very good improvement. You might argue, well, Eylea after a load might improve nine letters too, but sure, it might have, but we did it after a single injection, not a full load. Correct. Of course, if you extrapolate and say, what about pivotal? Yeah. If we run a non-inferiority trial, remember, we don't have to be better than Eylea. We only have to tie them. Got it. To get a label. Yeah. And if we do tie them and get a non-inferiority label, but we show some degree of visual acuity superiority, I think our market share will be very, very big. Got it. Got it. So this was an interim read, so we're gonna get the six-month read most likely in Q1, right? So early next year. What we should expect from that, how much additional information we need to learn or we'll learn, and is that needed before you sort of communicate to us your development plan for DME? I think that last point is the most important one. What we're looking for internally, as a company with the six-month data, is how does this help us plan our pivotal trials? That's really it. We've shown at month four how effective our drug is. Directionally, we announced with the PR that the finishers, 2/3 of them had finished by that time. Directionally, the same things we're holding with visual acuity, OCT. Yeah. Rescue rate and safety. So that I think, externally, there's no real, we've shown it already. I don't think the six-month data is gonna be that important necessarily. On the other hand, internally, to help us plan what we're gonna do, for the pivotals and then, of course, write the protocols, get alignment with the FDA, and then execute. That's really the plan for next year. Got it. The size and scope of the phase III would be similar to wet AMD or it's gonna be smaller studies? It could be smaller. Again, you know, if we ran a superiority trial, it's potentially smaller. I see. And one of the questions we're gonna ask the agency, of course, is, can we do one pivotal instead of two? And so, I certainly would not anticipate that even if we did a non-inferiority trial, it would be much larger than what we're doing in wet AMD right now. Yeah. Yeah. You mentioned 40% of the market. I think our research suggests it's about 35%, so it's a pretty big market. Yeah. Yeah. Yeah. I was being a little more liberal. I guess I shouldn't say that word. I was being a little more conservative. Conservative. What is the read-through to wet AMD from this study? I mean, I remember when you announced the NPDR data, people thought there were read-throughs, so now these are positive data. So what are the read-throughs? I'm gonna be consistent. When I said NPDR is a different disease, there's no read-through to wet AMD, I'm gonna be consistent. DME is a different disease. One could argue there's no read-through. Our wet AMD data is terrific. It stands on its own. Got it. But what this does is gets rid of the myths that had come up out of the NPDR data. Your drug may not work in diabetes. In fact, it may work better in DME than it does in wet AMD. Yeah. Your drug needs a load. No, it doesn't. Your drug isn't biologically active right away. Yes, it is. Your drug can't dry wet eyes. We dried wet eyes at four weeks better than a shot of Eylea did. Yeah. Yeah. Indeed. Okay. Moving on to wet AMD, what are the key differences between the DAVIO 2 and then the phase III LUGANO and LUCIA program? Sure. So, to remind everybody, we had designed the phase II trial after a Type C meeting with the FDA in 2022 because we had been at the time considering potentially going directly to pivotal from the phase one. We obviously elected not to do that. But the learnings from that Type C meeting and what we had agreed on with the agency really guided what we did in DAVIO 2. So talk about the difference. The first obvious difference is that this will be a one-year efficacy trial. The efficacy readout in DAVIO 2 was eight months. It is a combined 52 to 56-week endpoint. That combined endpoint is something that the FDA insisted on, and we did that in DAVIO 2 as well. Second big change, we are reinjecting our drug every six months and that we will go for it every six-month label. We are running a two-year trial. The second year is safety only, not efficacy, and we are able to submit our NDA after the one-year data. We are also now enrolling a naive population along with previously treated in the pivotals, and the reason we're doing that is we believe it will increase our rate of success and increase our label, that we should be, we hope, if approved, and, tolerated, that our label will read something like, for, previously treated or naive wet AMD patients maintenance therapy after three injections of an anti-VEGF. I think it'll be quite simple and simple for the doctors and the patients to understand. The other thing that became clear to us as we analyzed the phase II data is that we enrolled a very tough-to-treat population in the phase II, and we did pretty well with it. But for most of those patients, the average number of injections over the year leading into the trial was 10. There was a high rate of supplemental injections in the Eylea arm despite every other month Eylea. And so it was a tough-to-treat population, and we did well. But the best way to enroll a population that was more indicative of the actual wet AMD market was to enroll naive patients. But I'll remind everybody, they won't be naive when they get our drug. Everybody gets loaded. Randomization occurs on day one. Everybody gets loaded with Eylea, and then at month two, after three Eylea shots, they get our drug. When is your drug given? 30 minutes? 30 minutes after the third Eylea at week eight, so month two. Okay. So in this study, you are re-dosing at a fixed interval of six months. So I think we do get questions from investors, what happened to the inserts that are there. So can you just talk about the risk that it introduces, when, how quickly these inserts get eroded or dissolved? So we don't believe there is any risk involved here. And the reason is repeat injections in and of themselves obviously are done all the time in retina. And so repeat injections at month six is not per se a risk. Our inserts are reliably out of drug in about nine months in humans and maybe in some eyes a little bit quicker, hence the six-month redosing. Okay. The inserts that we're using in the pivotal trial, I mentioned it for the DME trial, they're now, higher payload, 1.3 mg, 1.34 mg to be exact, and they're 94% drug. So at nine months, only about 5% of the volume of the insert remains in the matrix. That matrix should go away in several more months. There will be individual variability. But, as I think I've explained, we've had three inserts in the eye of close to a hundred patients with no safety issues, no concerns. And if you run the math on two inserts, which is our high dose, every six months, and even accounting for many, many months for the matrix to go away, you reach a steady state of less than 2.8 inserts by weight and volume at steady state every six months. I see. So it's just, it's just not a concern. Yes. It really isn't. Okay. Very good. Now talk about the enrollment. How we should think about the enrollment timeframe for both the studies. I think the second study is also gonna start relatively soon, so. Yes. We did announce, at the time we announced enrollment of the first trial, that the second trial should enroll its first patient before the end of the year. We have guided to full enrollment sometime middle of 2025 with top line sometime in the middle of 2026. That guidance continues. I can say that out of the gate, we expected rapid enrollment, and we're actually ahead of what we anticipated with just a few weeks of enrollment occurring. Got it. Are these global studies? They both will be global studies. That's correct. Have you gone outside the U.S. yet or just U.S.? We haven't opened up any outside U.S. sites yet, but that will be occurring in the next few months, and it's a bit of a rolling basis as you may be aware, depending on the country, there's various stability studies and other things that you need to do to get a study up and going. So it will be. It's competitive. Yeah. But on a rolling basis. What I mean by that competitive, when we're fully enrolled, we're fully enrolled. And so if a site is slow to get going, that just means they may not be a part of the trial. So these two studies are needed. So, would that be the only requirement from a regulatory standpoint or more work needs to be done before you could file once the data are, if the data are positive? I don't believe there's any more work we're gonna need to do. That's all. No. Yeah. Anything specific? I mean, I think if you just look at the competitive, what I'm trying to get to is speed to market matter. If you look at the TKI competitive space, who will be first to market, you know, that's what I'm trying to sort of understand. We're confident that we're in the position to be first to market. Again, we're running two approximately 400-patient trials. Mm-hmm. But we're running them near simultaneously with different sites, globally, with planned up to a, up to perhaps 150 sites in each trial, and because we randomize on day one, there's no second hoop for the patient to jump through to get into the trial. In other words, they, they don't have to show any improvement after two shots or something like that, so I think that our rate of screen failure will be consistent with other trials and, and not higher than that. Got it. With regard to Europe, have you had discussions with the Europeans? Are there inputs in it? So not only just on the execution front, how are you thinking about that market? Is that something you sort of monetize it? You know, as you know, it's fragmented, the market, and the discussions come in two forms. The first discussion we've started is getting approval to run the trial in Europe. Mm-hmm. Getting approval to run a trial is different than agreeing that your package will be accepted and this is okay, and even after that, getting it paid for in the various countries is variable, and we're already starting, we have started that process to have discussions in the various markets about what they would be looking for and how we can best position ourselves, but the idea overall of a sustained release option is even more welcome in Europe than it is in the United States. Got it. They really want to cut down the number of injections there. Got it. Got it. Maybe George, if you can comment on the market dynamics there, how you're thinking about that sort of region. Is it something you'd outlicense it or just keep the asset with you? How are you thinking about funding the company if we need it? Yeah. And I think, you know, just to add to that point on the E.U. is that we expect that our trial should qualify for approval in the E.U as well as the U.S. And so as we think about, you know, the markets globally, you know, we're still a small company. And so I think as we look at E.U. and rest of the world as a partnering strategy makes the most sense. Mm-hmm. When and if we pull that trigger, I think remains to be seen. I think importantly, we're in a great position today from not just an execution perspective, but also a cash perspective. We did a financing two weeks ago, raised $160 million, which put our cash guidance into 2027. So we're in a great position. We're not in a hurry, and we're gonna be data-driven as we think about doing those transactions. Got it. Then, Jay, on the commercial dynamic, can you just talk about, now we have the high dose Eylea available, the VABYSMO available. How is the market gonna shake out once you are on the market and what type of patient will start on these TKIs? Yeah. So I think the good news for us is, as expected, the longevity that we're seeing from VABYSMO and high dose Eylea is not what was, let's say, set up by the pivotal trials. So, last spring, RCA, which is the largest private equity retina group in the country with 220 retina docs, published their results of switches from 2mg Eylea to VABYSMO in wet AMD. They got out eight more days with VABYSMO. Last month, the Bascom Palmer group published their switches, which is they took all their wet AMD eyes that it didn't matter what they were on, but bevacizumab, LUCENTIS. When they switched them to VABYSMO, they asked the question, what percentage could get out two more weeks or more? Only 15% could get out two more weeks or more. So as expected, these drugs are gonna do well because the market wants more longevity. Yeah. But they're not approaching six months and that we offer something that they cannot, which is maintenance therapy for what we believe will be the majority of patients for six months or longer. Yeah. We also offer a different MOA. You can ask this question, but I'm gonna say, well, why did we do so well in DME? It may just be that treating with two MOAs is beneficial. Beneficial. Maybe that blocking C and D VEGF is beneficial. We do block C and D, and so that, while I can't say for sure we need to do some more work on why it was so beneficial, but those are things that obviously can help us in the market and in the real world, those two who will be the market leaders presumably two years from now. Yeah. Don't offer. Got it. So in some of the research that we have done on market research that we have done, the KOLs have commented that somewhere between 25%-35% or maybe 40% of their patient could be eligible or get transitioned to a TKI. Is that something similar to what you hear? Just curious to understand from your perspective. So we actually did a study on that as well, and that is very similar to the number we came up with, but we did that study with a TPP that was worse than what we came, what we had from DAVIO 2. So we did the study prior to DAVIO 2 outcomes, and we got the same figures, 25%-40% market penetration in wet AMD. We're doing this study again with the data that we got from DAVIO 2, and we only expect it will be higher. The other thing I'd like to emphasize is our safety, that is really important to doctors and really important to enter patients into trials and to switch to a new drug. And we've treated over 190 patients without any safety issues at all, and that's not lost on the marketplace either. Got it. With regard to the, actually, what is the IP first? So Vorolanib has patent protection out to 2037, which we believe can be extended to 2042. It's never been approved in the United States so that we get the new drug exemption for five years that could be extended to seven and a half. And we have, patents that we've applied for with a combination of Vorolanib and Durasert E, multiple patents. And we also have a new injector that's under development that we will, get patents around that when, when we bring it to market. Got it. And this is an NDA or a BLA? It's an NDA. NDA. We're not a biologic. We're a small molecule. Yeah. By the way, we manufacture it ourselves. Excellent. And we just opened up, as some of you may know, a new manufacturing facility last week. Nice. Very nice. It's a busy week. Yeah. New data. New data. Raise in a new manufacturing facility in three days. Yeah. How long it will take you to file an NDA? Is it like about a six-month timeframe after we have the study result from this? We've guided to one year. One year. Not, I'm sorry, not to file. I'm sorry for them to respond. We think we can file it, in a rolling fashion probably, certainly in three months, probably less than that to get it all in. Yep. Okay. All right. What else, what about 1902? Oh, 2302. 2302. Yeah. So, EYP-2301. The TIE. It's a TIE-2 agonist. You don't wanna inhibit TIE-2. You wanna agonize it. When you agonize TIE-2, you downregulate Ang-2, which is what presumably gives VABYSMO a little bit of an advantage. But you also upregulate Ang-1, which leads to vascular stability. We do that through VE-PTP. The VE-PTP is the receptor. This is a molecule that was studied. It was formerly called AKB-9778. It was studied by Aerpio Pharmaceuticals in Diabetic Macular Edema and DR, as a subcutaneous injection. Mm-hmm. And it showed actually quite good anatomic data. The visual data as an add-on to LUCENTIS was not as impressive, but we've been able to reformulate it so that it can be sustained release for six months or longer with a single injection. We are still preclinical with that. We have some other studies that we need to do prior to doing some definitive IND enabling studies. But we hope to have some more information this year on that. Got it. Maybe final question for George. So with the recent financing, like how's the balance sheet looking? Yeah. And anything you could do to sort of spend more money and accelerate the timelines? So two great questions and one there. We're really happy with our balance sheet. I think as the group knows, we ended September with $253 million in cash, did $160 million gross financing two weeks ago. We've increased our cash guidance into 2027, which is, you know, roughly nine to 12 months after data for the wet AMD phase IIIs. We've included in that cash guidance some early work to support our clinical team and manufacturing to gear up for potential DME trials and also do what we can to accelerate. I think, you know, kudos to our clinical team who have really focused as much on getting that last patient second trial in, in wet AMD as first patient first trial. We're really, you know, focused on doing what we can to accelerate. Very good. I think that's all I had for you. Great. Thank you, Jay, George. Thank you. Thank you very much. Thank you. Thank you.