Great. Thank you. Good morning, everyone, and welcome to the EyePoint Pharmaceuticals session. It's our pleasure to have CEO Jay Duker with us to give the full presentation. EyePoint is a phase III development company with several programs for both wet AMD and now DME. The first data are emerging wet AMD, I think, in 2026 already. We're not that far away. About 10 months. Mid-2026, yeah. Jay, why don't you go ahead and give the presentation? Thank you very much, and thanks for the invitation. EyePoint is the leader in sustained drug delivery to the back of the eye. As you just heard, we are in phase III now in two indications: wet Macular Degeneration and Diabetic Macular Edema. The phase III wet AMD trials are fully enrolled, and the top line for the first trial will be mid-summer, with a second trial to follow. We plan on dosing the first patients and randomizing them in the first quarter in DME of next year. We've had excellent efficacy and safety through our four prior trials: one phase I and three phase two trials. DuraCert is a proven technology. It has been in four FDA-approved products. We've been really concentrating now on commercial scale-up and also commercial success. Strong balance sheet with a mid-$350 million in cash, giving us a runway into fourth quarter of 2027. This is our pipeline, which I think I have essentially fully covered. Wet AMD in phase III, readouts next year. DME starting first patient i n the first quarter of next year. We believe we should be able to have the top- line readouts of the two DME simultaneous trials in the fourth quarter of 2027. We also have a pipeline asset, which is EYP2301. ResprotaFib is the small molecule in our sustained-release formulation, and that is still preclinical. Between wet AMD and DME, that is 80% of the branded market in anti-VEGFs. This slide really summarizes the technology of DuraCert. We do have four FDA-approved products. You can see them on the left. We no longer commercialize any of them. Duravyu is in our Durasert E product, and this is essentially a new and state-of-the-art delivery system. What's new about it is that it's now 94% drug, only 6% matrix. The matrix contains no PLGA. It contains no PEG. I have mentioned this, but we've been testing this in phase II in our Verona trial. What are the advantages of Duravyu? First of all, our drug, Vorolanib, is a multi-MOA drug. It not only blocks all VEGF receptors, but it also blocks inflammation through the JAK1 receptor. We get immediate drug levels in the choroid within hours of injection and sustained consistently over at least six months in humans. The drug release is controlled. The inserts, essentially, they're heavier than water. When they're injected into the vitreous cavity, they sink to the bottom, and they essentially melt away. There's no free-floating drug particles at the end. It's also convenient. Our injector system is preloaded sterile, and it can be shipped and stored at room temperature. That may not sound like a big advantage, except when you go into a retina specialist's office and you realize that they have these huge refrigerators to store all these biologics, with more coming. Of course, gene therapy requires a minus- 80 freezer. This is a summary of the four trials that we've completed. The Davio trial was phase I wet AMD. Davio II was the largest wet AMD sustained-release trial to date, with 161 patients enrolled. Pavia was NPDR, and the Verona trial was our phase II Diabetic Macular Edema trial. The primary endpoints were hit in the wet AMD and DME trials. The other big issue with all retina drugs is safety. Not only have we seen so far in these four trials, we had no ocular or systemic SAEs. There are also no safety signals. Now, if you take a step back and say, "All right, what are you trying to do?" Obviously, you've got a sustained-release platform, but is that the only unmet need in these diseases? The answer is no. It has become apparent that inflammation plays a role in both DME and wet AMD, and having an anti-inflammatory component appears to give better results, especially in DME. We believe that our inserts will not only solve the maintenance issue of keeping patients in treatment long-term to improve visual outcomes, but also Vorolanib is going to offer this anti-IL-6 benefit. How do we know that VEGF isn't the entire story? If you look at this graph on the left side, this is from the Harvard trial, which was a study of high-dose Lucentis in wet AMD. What they noticed is eyes at two months that had their aqueous sampled. In their aqueous, the eyes that had the highest levels of IL-6 did poorly, in fact, lost nine letters over two years. It does appear that IL-6 is a biomarker for poor outcome in wet AMD. It's probably even more important in Diabetic Macular Edema. On the right is a curve from a study that was published. These were patients who underwent vitrectomy for various indications. The eyes that had Diabetic Macular Edema had significantly higher levels of IL-6 than the eyes without diabetes or diabetics who did not have retinopathy. Recent data has shown us that our drug, Vorolanib, not only blocks VEGF and PDGF through the receptors, but also blocks all four of the JAK receptors. What you're looking at on the left side of the slide is the human kinome tree. The branch at the bottom right is the one that we're interested in, in the back of the eye. You can see the blockage that we've shown in the four JAK receptors, but especially JAK1. In the middle is a steric representation of how Vorolanib fits into the ATP binding area of JAK1. We took it a step further. It's one thing to say in the laboratory you've got, you know, you're well over the IC50 for a receptor, but ultimately what we care about is blocking IL-6. We did a cell-based assay where we added IL-6 to the cells and looked at the downstream effects of the IL-6. Obviously, it controlled. It was 100% activity. When we looked with Vorolanib, about approximately the doses we're getting in human vitreous, we showed over a 50% reduction in IL-6 activity. We did test sunitinib and axitinib in this as well. While sunitinib had a mild effect of about 10% reduction, axitinib had no effect on IL-6 activity. Vorolanib is a potent TKI, novel multi-MOA, and you can see on the graphic the five receptors that we believe are most important in both wet AMD and DME. Let's talk a little bit about our wet AMD trials. The two trials are called LUGANO and LUCIA. They're identical. They're phase III non-inferiority trials. The only difference is LUGANO was fully enrolled in the U.S. LUCIA was approximately 80% U.S. patients and about 20% ex-U.S. Both trials are fully enrolled. Each trial enrolled over 400 patients in approximately seven months, which for wet AMD trials is essentially the fastest phase IIIs that have been reported to date. We have noted that so far, the DMC and the MAST look at safety pooled shows no safety signals. In these trials, all patients get active treatment. So far, the dropout rate in both trials is very low. It is very low single digits. The LUGANO trial, which was the first to enroll, will have top- line data mid-next year, and LUCIA soon to follow. This is the schematic which shows the outline of the trials. The important thing to note is all the patients get loaded with Eylea monthly. At week eight, they either receive a dose of 2.7 milligrams of Duravyu or they receive a sham injection, and then they're seen monthly. Every other month, the Eylea arm gets another Eylea injection, and the Duravyu arms get a sham for masking. At the six-month anniversary of the first injection, Duravyu is re-injected. This is a two-year trial for safety. We're able to submit the NDA after one year. The primary endpoint is change in visual acuity at week 52, 56 averaged. The averaging of the endpoint is something that the FDA strongly suggests, and we believe de-risks the result. On to Diabetic Macular Edema. You're looking at graphs here from our phase II Verona trial. The Verona trial tested two doses of Duravyu, 2.7 milligrams and 1.34 milligrams. Again, this is a higher payload, so this is the first time we used it in humans. The red box outlines the change in vision at the top and OCT below between our drug, 2.7 milligrams, and Eylea. On day one, all these DME patients got an Eylea shot, and the patients that were randomized into our arm got, in addition, 30 minutes later, their Duravyu. That difference that you see at week four is purely our drug. This difference is what made us go back and ask the question, why? Eylea is an excellent anti-VEGF. Why are we getting four letters better and 40 microns drier at week four? The answer we believe is the IL-6 blockage that Vorolanib provides. Throughout the study, at the endpoint, notice that the visions ended up about the same, seven letters better. This is a previously treated group. If you go back and ask how do previously treated DME studies out of the eyes do, they gain about five letters at six months, most recently seven letters at one year. This is consistent. Also notice, however, that there was a big change in the 2.7 milligrams between week 20 and week 24. That was a single patient who missed the visit at week 20, came in at week 24, down 22 letters, subsequently got rescued, and the vision came back. Without that outlier or had that outlier come in at week 20, we would have had about a 10-letter improvement in the vision. That is the curve without the outlier. What is really striking here, too, is if you look at the symmetry between the visual acuity improvement and the OCT improvement, that's why I think you can really be reassured that this is a real finding. Visual acuity can be somewhat subjective. OCT is not. When the structure and function are aligned like this, it's a real finding. We also took a look at the patients who were rescue-free, meaning they got Duravyu at day one, and they got nothing else afterwards. It was over 70% of the 2.7 milligram arm. Notice that that was over 10 letters improvement, much better than the rescue-free rate of the Eylea. It was 120 microns improvement in the OCTs. What does that mean? A normal OCT is up to about 325 microns, and these eyes started at about 420. On average, the eyes became normalized using our drug alone. You may be aware that IL-6 is something that's being looked at by other companies, including Kodiak and Genentech. They both have biologics on a monthly basis that block IL-6. This is from the recently reported BARDENA study, which is Genentech's phase II in DME. What you're looking at is the curve of the visual acuity improvements on Lucentis monthly alone. When you add an IL-6 blocker, you get immediate better vision, and it appears to be sustained over the six months. Now, I'm going to superimpose our results from the supplement-free arm. This is our drug alone after day one. Notice it's almost exactly the same as the combination. What's the difference? We did it with two injections. They did it with 12 injections because they're monthly. If we can show the same kind of result in the phase III trial, I believe we will have a potential blockbuster drug in DME. This is a graph that shows the results of leakage from the Verona trial. Leakage from the capillaries is a sign of capillary instability and inflammation. This is measured with a fluorescein angiogram quantitatively by a reading center. You can see there is a dose response here between our low dose and high dose, with significant reduction in leakage compared to the Eylea control. Finally, this is one of the patients from this trial. This is a patient with active DME, and you can see what the patient received in the top right of the trial leading into the study: one Avastin and then six monthly VABYSMO If you have an eye that you're treating with monthly VABYSMO and you can't treat and extend, I think you can make the assumption that this eye isn't responding to VABYSMO well. In fact, the top left OCT shows that center cyst of fluid. This is about two months after the last VABYSMO. This patient was enrolled in the trial 2.7 milligram arm. You can see between the time of screening and the time of enrollment that cyst got larger. What happened? One month later, the cyst is smaller, and bottom right is the end of the trial at six months. The cyst is gone, and the visual acuity improved eight letters. This is an eye that not only did better visually, better anatomically, but lasted longer than VABYSMO. Think about that. How many of these eyes do we have to have in real practice before we become the standard of care in DME? The DME program is up and running. We will, again, dose the first patients in both trials in the first quarter of next year. The two trials are called COMO and CAPRI. They're identical trials, and they will enroll approximately 240 patients randomized into the 2.7 milligram arm of Duravyu or Eylea on- label. Once again, I want to emphasize that the agency has been very clear. If you want to run a non-inferiority trial, you have to run it against on- label Lucentis or on- label two milligram Eylea, no exception. The primary endpoint is similar to the wet AMD trial, non-inferiority change in visual acuity at weeks 52 and 56 combined. Obviously, we have secondary endpoints of safety and reduction in treatment burden. Here are the key elements. We had a highly positive phase II Verona trial that informed us about how our drug does and helped us determine the size of the trial. We are leveraging the pre-existing clinical trial structure of our wet AMD trials, both the sites and the CRO. There is really a lot of physician enthusiasm for this type of treatment for DME. This is the outline of the DME trial. I think you'll notice it's very similar to what I showed you for the wet AMD pivots. Again, two identical trials. One of the big differences is we dose Duravyu on day one, not week eight. The reason we're doing that is we would like to show that at week four, we had better vision. If we can show that we're non-inferior to on-label Eylea with a reduction in treatment burden, but we achieve better visual acuities faster, we think that's going to be very powerful commercially. Again, the primary endpoint is at approximately one year. We'll be able to submit the SNDA at that point, but it's a two-year trial for safety. Note, this is an SNDA. If you're wondering why we can do this with relatively fewer patients, the answer is the agency has allowed us to use the safety database from wet AMD to inform the safety here. We don't have to do a large safety database in DME, provided the wet AMD safety continues to look good. That's in contradistinction to most other DME trials that have been run simultaneously with wet AMD trials. That is why the 240 patients statistically is sufficient to show the result. In summary, we're in a position to be first in class and best in class in the two largest retinal indications. We've had robust phase I and phase II efficacy and safety to back this up, favorable safety profile in over 190 patients treated with Duravyu to date, with no instances of visual loss due to our inserts, no instances of patients requesting the inserts be removed, no insert migration into the front of the eye. The wet AMD trial is fully enrolled with data initial in about 10 months. DME trials, we should expect to fully enroll in the second half of next year. On the last note, I do want to show you some pictures of our commercial facility. We're based in Watertown, Massachusetts, and our inserts were previously all made in the Watertown facility. It became apparent to us about four years ago that the Watertown facility would not be able to make enough inserts for commercial success. We scoured the East Coast and came up with a location in Northbridge, Massachusetts, which, if you're looking on a map, is right next to Oxbridge. It's a 41,000 sq ft facility built to our specifications from the ground up. We actually had a deal with a landlord, so we didn't pay anything out of pocket for this until we took possession of it about a year ago. We really conserved capital in this deal. This meets FDA DMA specifications. When we're fully up and running, we should be able to make hundreds of thousands of inserts a year at this facility. We've completed registration batches here, and we're really preparing for pre-approval inspection. We're really looking downstream to commercial success. I'm happy to entertain any questions if we have time. Sure, of course. I guess one of the key questions we have is, what would your ideal profile be for DuraCert in order to shift the retinal practice over to TKI versus anti-VEGF? I know that retinal specialists are very keen on reduced dosing, but you've got a different molecule. Help us. Yeah. I'll answer it in two ways. I think if we are non-inferior and we're safe and we have a reduction in treatment burden, we will capture a lot of the wet AMD and DME market. That in and of itself. The answer, again, as you said, the doctors are inundated with injections. With the complement drugs really coming on board more and more, there's just no room in their offices. They'd be very happy to offload patients from a monthly or bi-monthly basis to longer. Remember also, the value here is not that we're going to take everybody out six months or longer. If you look at our phase II data and you extrapolate, and it holds, we could probably take two-thirds of the wet AMD population out that long on our drug alone. Doctors may choose to use us together with a ligand blocker. There's no reason that they can't. You never hear about someone using Lucentis and Eylea alternating because they essentially do the exact same thing. We're a different MOA. Not only do we provide that anti-VEGF activity with a different MOA, we block PDGF, which means we may be antifibrotic. We may be neuroprotective. We showed that in a preclinical model. Now this IL-6 blockage really is a differentiator for us. Ultimately, I think we can capture a lot of market share if we're non-inferior. It does not mean that we might not be actually numerically superior to Eylea or even statistically superior. That is a stretch. Obviously, if that happens, then everybody's going to use us. Okay. Just a quick question on that point where you think you can treat two-thirds of that, take two-thirds of that population. What is the threshold that you're looking for? What are you powered for, as far as, you know, I know non-inferiority, but what are you looking for in terms of reduced injection, the percentage of population? That is a good question. What we're looking for and what the FDA is looking for is a superiority of reduction in treatment burden. I think if you look at it in the real world, where a supplement isn't a failure, you can't think of it in those terms. If I'm a retina specialist and I've got a patient that I'm injecting monthly and I use Duravyu, but I need to supplement every three months, that's a win. That's four shots a year instead of 12 shots a year. Plus, I get the two MOAs, I get the insurance policy, I get the, which, you know, the insurance policy I like to talk about. These are elderly patients. If you have them treat and extend it out to three or four months, and they miss a visit, they may come in six months after their last ligand blocker, where they clearly could be worse. Having a sustained release option really will make patients and doctors feel better about that. It is not an either/or. It is a new way to look at the treatment of these chronic diseases. Ultimately, what we believe is using what you could refer to as force compliance is we should get better visual results in the long term. One thing that you are doing in the DME trial, which is giving Duravyu the day you give either Eylea or Lucentis, the anti-VEGF, you see the letter benefit. You're not doing that in the wet AMD, I believe, because the trials were already designed when you found that, had that finding, maybe, but maybe you can describe why one is different from the other. Yes. It's a really good question because we can go back in time and say, why are we loading? Do you really need to load? We showed in the DME trial, we didn't need to load at all. Our scientists will claim that we don't need to clear the eye of VEGF at all. It's a matter of risk reduction. When we did the phase I, we gave everybody an anti-VEGF on day one, and a week later, they got our drug. Why? Because we wanted to level the playing field. Now, if you have a patient who comes into a trial with wet AMD that has fluid, you do not know if they are a poor responder or did they just go too long between their last injection. We wanted to level the playing field, and it worked fine. When we went to the FDA in 2022, we had a Type C meeting because we were contemplating going directly to Pivital back then. Glad we did not, but we were contemplating it. We asked the usual questions. When we got to the dosing of the control group, and we said every other month Eylea, the agency said, "No, you cannot do that because you have to dose Eylea on label. If you are going to do a non-inferiority trial, you have to reload the patients even if they are previously treated", which we said fine. We're happy to do that. Then we went back and said, "Can we reload everybody?" The agency said, "Go ahead.". Whatever you do at the beginning of the trial, and you finish the load at month two, it's going to wash out by the end of the trial. The consequences of that reloading is our endpoint is 56 weeks. You can do an endpoint of nine months in wet AMD. We, again, because we chose to load everybody, it was a one-year endpoint. Once we did that in the phase II, we weren't going to change it for the phase III, even though we believe a full load is not necessary. Okay. Great. I'm going to talk slightly, I guess slightly controversial question is interpretation of guidelines and how each of these trials are designed just a little bit differently. Maybe we can hear your understanding of the FDA guidelines and how these trials should be designed, and what may or may not happen in the landscape. First of all, there are draft guidelines. Yeah. Okay. Draft guidelines. They have not been accepted even now. Draft guidelines are just that. When you talk to the FDA, they will say this is for public presentation in comment. Draft guidelines do not have to be followed. In saying that, we've had two meetings with the FDA, a Type C meeting in 2022, which I already mentioned, and a phase II meeting in 2024 around wet AMD. We have been aligned with that. I do not think there is any controversy. I think it's all actually pretty straightforward. Maybe there was a poor characterization. Yeah. The agency has been very open and straightforward about what they want. I mentioned it already. They have told us on multiple occasions that if you are doing a non-inferiority trial in either wet AMD or DME, you have to use an on-label control of either Lucentis or Eylea 2 milligrams. Why? Because those are the drugs that gave us the non-inferiority margin. You cannot go against VABYSMO. You cannot go against 8 milligram Eylea because they did not get the non-inferiority margin years ago when View 1, View 2 was actually done against Lucentis. There is really nothing else controversial about the draft guidelines. Okay. Great. I guess not controversial, I apologize. With the profile that you're looking for, you have a number of patients who are going to be able to get to six months and some who will drop off to three or four months and would need rescue. You have VABYSMO, you have Eylea HD. What is the incentive for those patients to have these two different mechanisms if they're still getting rescued at three or four months, which is around the time that VABYSMO or Eylea HD is sort of their duration? Except it isn't. Real world, again, I think you can look at the data that's come out. Depending on which study you read, VABYSMO has offered either eight days longer of duration or about two weeks longer of duration. That's the real world. Real world. That's exactly right. The studies were designed in a way that eyes could go out longer with fluid and decreased vision as long as it did not reach a certain endpoint. If you look at the VABYSMO trial, half the patients, 50%, could not get out beyond eight weeks. The ones, the 45% that made it to four months, what they really, because everybody got retreated at four months, what it really meant is at month three, you did not meet the criteria to get a retreatment. You could still have had fluid and decreased vision. You did not meet the criteria. If you look at our data and ask, well, how many of your eyes made it out without a supplement to month four? It is 75%. If we are non-inferior and safe, tolerable, and we have no other benefit, I think a lot of doctors and patients will choose to use us because if you're already getting treated every month or every six weeks or every eight weeks, the idea of going out six months, even if you need a supplement in between, is attractive. If we can show those other benefits, anti-fibrosis, better vision results, neuroprotection, then I think we're going to be used in the vast majority of patients. Okay. I guess one other question, as far as the rescue definition. They're all also a little bit different. Can we just hear your definition of rescue? Oh, sure. First of all, in the real world, no one has rescue criteria. If you ask a doctor, when do you retreat, you'll get every doctor you ask you get different answers. The reason is we individualize therapy. We do not do it by a book. If you have a patient who has poor vision in one eye and they get a little fluid, new fluid in the other eye, you are treating, and you are never going to go out that long again because you cannot risk that other eye. Versus a patient who says, I come from three hours, and my other eye is good, you might tolerate a little more fluid. The whole idea of rescue or supplement criteria is not real- world. We all admit it. We need to have something that we stick to to make it quantitative. Our rescue criteria is simple in the wet AMD phase III. It is the loss of five letters from best on study with 75 microns of new fluid. You are correct that the FDA does not mandate the same criteria for everybody. You can do what you like, but that also will be interpretable with regard to your study. Okay. I know we are out of time, but just one last question. CASH, where does that take you? Can you complete all your phase III trials? CASH takes us out to Q4 2027. Yes, that includes all four of the phase III trials. Okay. Great. Thank you very much. Thanks for listening.