Thanks for joining our fireside chat with EyePoint Pharmaceuticals. I'm Jennifer Kim, one of the biotech analysts here at Cantor, and I'm excited to have with us George Elston, CFO. George, it's always good to have you. Thanks for being here. Thank you, Jennifer, and thanks to Cantor for having EyePoint here today. I'm excited to talk to you. Always. So a lot of exciting things happening at EyePoint right now. Maybe to kick things off, can you give us a quick overview of the company and where things stand with DURAVYU, your lead asset? Sure. So, for those of you new to the story, so EyePoint, our focus is on being the leader in sustained delivery of therapeutics to the eye, leveraging our Durasert delivery technology. And, you know, we've had a number of one-on-one meetings today, and I think what's really come to the forefront, and a lot of people have reminded us, is, you know, our DURAVYU journey started about four and a half years ago when we had our first phase I trial, and we were last. There were a lot of TKI companies and others, just sustained delivery companies ahead of us. In that four short years, we've completed one phase I, three phase IIs, and most recently enrolled two global phase III trials of over four hundred patients each, and we've gone from sitting in last place to really being first. We expect to be the first to read both phase III trials out next year, first to file NDA and hopefully first to approval and launch in 2027. Yeah. Execution has definitely been a theme for this company. Fantastic execution by the company and Ramiro on getting those phase IIIs enrolled so quickly. Over 400 patients in each trial, randomized in seven months. I think you've said LUGANO randomized 432 patients, and have you said how many patients are randomized in the second trial? We haven't come. We're still. So LUCIA was just fully enrolled in July, and so we don't have the final number on that that we've disclosed publicly. It's certainly gonna be north of 400 patients, much like LUGANO. The beauty of these trials, and we were, you know. We had great expectations for these trials, and the enrollment even beat our expectations. You know, on average, wet AMD trials take about 12 months to enroll. We did each in 7, and we broke records on our enrollment rates of site, per patient per site, per month. What was unique about the LUCIA trial, and that was, the LUGANO trial enrolled so quickly that it was U.S. only. LUCIA, we were able to get ex-U.S. sites, so we had sites in Europe, Israel, Australia, Latin America. As we got toward the end of that trial, the we had visibility daily to screening, and the screening numbers just kept going up and up and up, and we, you know, we were pushing Ramiro's team, like: "You know, you're gonna need to let people know soon you're closing screening." When they did that, the numbers went through the roof. We are very patient-centric in our clinical trial approach if you look at our trial design, and so we allowed those patients to come in. We feel really good about our powering and our total N for both trials. Okay, and then LUCIA includes ex-U.S. patients. I think you said the first ex-U.S. patient enrolled in June. Then what's the final breakdown between U.S. and ex-U.S.? So in LUCIA, it's about 80% U.S., 20% ex-U.S. Between both trials, it's gonna be about 90% U.S., which I think is important for U.S. FDA. They like a majority of patients in the U.S. Plus we have, you know, these other sites. Keep in mind, wet AMD is a genetic disease. We have the same protocol approach for all sites, and so we don't expect any differences in the populations. Okay, and then just remind us what the trial designs look like, and are there any key differences or protocol changes you would flag for those trials? Yeah, so, this is the beauty of why you do a phase II, which we did at EyePoint. DAVIO 2 was a phase II trial. It informed our phase III. It informed our phase III on our stats, on our rescue criteria. And so when we kicked off our phase III program, both LUGANO and LUCIA, they're identical trials. We've made zero changes to our protocol since inception, including our rescue criteria, which has been unchanged. It's five letters with 75 microns of new fluid. That's an important criteria because we want to protect vision around that non-inferiority margin. There's no investigator discretion in the phase III, and that's important because when we looked at our phase II, 20% of the supplements in phase II met essentially no criteria, and those associated with other matters like fluid, for example, had no effect on vision, so we wanted to make sure that patients were getting treated, we were protecting vision, and so as a result, we do expect to see an improvement in rescue-free and overall treatment burden reduction. Okay, and with the phase II trial, can you tell us what we saw in that trial and what other learnings you've used for the phase III program? Yeah, so just as a reminder, the DAVIO 2 trial was a single injection of aflibercept at two different doses, two mg and three mg, against the aflibercept on label. That was a single dose in all previously treated patients. And in that 160-patient trial, we were statistically non-inferior to Eylea at month six in both the low and high dose. In fact, there was virtually no difference between the low dose and the high dose. And as a result of that, we've moved forward in the phase III with a single dose, which is our 2.7 mg DURAVYU dose. What was important about that trial is it did give us our statistics. It informed our phase III. A s I mentioned earlier, it did help inform us on what supplements made a difference and why, and how we want to control for that in the phase III. So looking between the phase II and the phase III, I think there are three key differences that people ask questions about. Compared to the phase II. One is, like you talked about, the rescue criteria. Two, in the phase III, the inclusion of both treatment-naive and previously treated patients. And then three, you have redosing in the phase III program now. Can you just walk through how one might expect each of those to impact the expected outcomes for the phase III program? Sure, so let's start with redosing. So that's important. We wanted to make sure that we had redosing on our label. FDA is very clear in their guidance on how you get redosing, and that is you need to have at least 300 evaluable patients at your go-to-market dose and interval. And so what does that mean for our trial? It is we're redosing DURAVYU every six months for two years, so there'll be a total of four doses over the course of the clinical trial. We'll submit the NDA with 12-month safety and efficacy, and then supplement that with the 24-month data. If that's positive, that'll give us an unlimited label for redosing. Going back to the treatment-naive versus previously treated, so what was unique about the DAVIO 2 trial is we got a really tough-to-treat population. If you look at the incoming patients, they had on average 10 injections per year going into the DAVIO 2. In the U.S., patients have about six injections per year. Despite that, we did really well in that patient population. We took 2/3 of patients six months on our drug alone. We reduced treatment burden by 80%, and in fact, that was not redosed, and even after a single dose, 50% of those patients went a full year. We got no easy-to-treat patients in that group. And as we went back and we looked at, we call them pseudo-naive patients, we did really well in that population, although it was a small n. And so as we looked at the phase III, we wanted to make sure that we wanted a broader label, so we included both previously treated and newly diagnosed. And if you think about in the clinical terms, patients that are well-controlled and coming into their doctor every three months, they're not gonna sign up for a clinical trial because why would you? And so in order for us to get those patients, because we know we did well on those patients in phase II, we've included newly diagnosed. That's also very important for the non-inferiority trial itself, in particular, the control arm. So FDA is very clear in their guidance on control. Your control group, everyone gets the minus four and a half non-inferiority margin. However, your control group needs to be on-label, aflibercept or LUCENTIS, and we're going with on-label aflibercept, and that's in our clinical trial design. Part two of that, however, is also important, and that is your control group needs to behave similar to those groups that were where the non-inferiority margin was established. And so that's also another reason why we've included these previously treated-- I'm sorry, these newly diagnosed patients, because we're, we know we're gonna do well with them, and it's actually gonna help that control group behave. And remember, we randomize on day one, and so we're gonna have that benefit of that load as well. So we're feeling really good about that phase III design. I think you said recently, did the FDA give similar comments when they were talking about DME? Yeah, so you know, the good news about the new FDA is they're still consistent, right? We've seen that with some of the recent interactions with companies in ophthalmology. When we met with them for DME, you know, they'll allow a non-inferiority margin, but you've got to enroll patients on label with aflibercept and DME, just like you have to do with wet AMD. They continue to be consistent, which is great because we've been following the rules as FDA outlines them, and that's what's in our phase III. All right, and you've already touched on this, but maybe putting into two buckets, from a regulatory standpoint, what does the FDA want or need to see in the Phase IIIs, and then also from a commercial standpoint, what do you want to see in the Phase IIIs? Yeah, and there's a lot of discussion between investors and investigators there. And it's different, right? So our clinical trials are designed for success. The FDA, the approvable endpoint in wet AMD is non-inferiority to aflibercept on label, and you have to be within minus four and a half letters. That's how our trial is designed, and that is the focus, and that's the clinical trial design. So there's a lot of discussion about supplement and rescue-free rates and OCT and fluid. That's important for a commercial, but the FDA is less concerned about that. They're focused on BCVA as the endpoint, which is why we've designed our trials the way that we have. Now, as it relates to OCT and fluid, you know, that's also important, and we've designed the trials so that we can minimize the supplements. We've taken away investigator discretion in the phase III because most of the supplements for fluid didn't matter anyway. And so that will certainly be important. The medical community is focused on fluid. The FDA is focused on BCVA, and I think as we look at the readouts from the phase III, we're gonna have data to inform both. Okay, and then commercially, you talked about decreasing the number of rescues. Sort of, what is the bar there, in your opinion? So yeah, that's interesting. That question's come up a few times today, and I can say pretty confidently there's no standard in the community for when do I supplement a patient? That's all individualized therapy. You know, you talk to retinal doctors, they tell you they don't read labels. And so, you know, historically, they've always been treat till dry. I think you're seeing a movement away from that, where some fluid, depending on where it is, is not a bad thing. And so as we think about our commercial launch, it's really going to be about where we fit in, you know, to the treatment regimen, and I think there's a number of different places where doctors will use us. You know, I think what's been interesting, and you look at different models out there for adoption, for TKIs, everyone's in that 20% to 40%, and then you see KOLs on the podium talking about 80% of all of their patients. So somewhere in the middle is where it's going to be, I think, as our commercial team continues to think about how our program is gonna fit in the marketplace. The important takeaway is we're not another anti-VEGF. You know, DURAVYU is a TKI. We block intracellular signaling of VEGF. We bind all VEGF receptors, and it's a different mechanism of action than any drug that's been approved in wet AMD in the last 15 years. You know, if you look at the history, each new biologic in wet AMD, their claim is, "We last longer than the prior version. Use us, don't use them." Our argument is very different. Our clinical trials are designed differently in the sense that our position is, pick your VEGF of choice. Remember, we're a different MOA. Pick your VEGF of choice. Get your patient stable, put in DURAVYU. If our phase two data holds, we're gonna take 2/3 or more of your patients every six months or longer with just our drug. If you need to supplement in between with a VEGF, go ahead. You'll get paid, you'll get reimbursed, and your patient's gonna go home with two mechanisms of action on board. Maybe stepping outside the U.S. Ex-U.S. makes up 40% of the branded VEGF market. How are you thinking about the regulatory path and the data package for the E.U.? Yeah, so, you may have heard, and we reported recently, that the EU signed off on our protocol for our clinical trial design, and if you know about the EU, they look at not just the protocol, but its ability to be used. So we've now been signed off by two of the largest regulatory agencies for our program, and we're working through our regulatory package for the EU. I think the commercial side is a slightly different story. So right now, we are focused on getting our NDA filed and launching in the U.S., and we've said publicly our focus is we're gonna do this on our own. We have done it before. We can address retina with a pretty small footprint, and we've got great relationships across the community. I think rest of world will remain to be seen. You know, there's a lot of noise out there on most favored nation, and right now, we're in a really good place. We will look for the partner at the right time, but we're certainly not gonna compromise the U.S. market in the near term. Okay, since you brought up the macro, can you talk about how maybe other headlines impact or don't impact you? I know you, you've put a lot of emphasis on your manufacturing capabilities. Just talk about that. Yeah, so, just to remind the audience, we are drug developers at EyePoint. We have been doing deliberate drug development since the inception of DURAVYU. We did a phase one. We did a robust phase two. For those of you who have been to our site, we have a beautiful facility in Watertown, but it's not large scale, and as we launched DURAVYU, we knew that we needed a bigger footprint. And so about four years ago, we started on this pathway for scale, and so we have a brand-new state-of-the-art facility in Northbridge, Massachusetts, 41,000 sq ft of commercial manufacturing space. We occupied it last fall. We are in the middle of registration batches, and so while all eyes right now are on data next year, and we're all excited about that, we're also excited about doing registration batches, getting ready for pre-approval inspection and getting commercial supply available. As we all know, a lot of companies stumble on CMC. That seems to be where all CRLs are, and we've been thinking about that for a long time. Part two of that, Jennifer, is we make this product in the United States. We control our destiny. You know, these are small inserts. Each insert, by the way, is one point three four mgs of drug and one five-thousandths of the vitreous cavity. These are small. And so we know we, you know, no one can make what we make. It's our expertise. We are scaling this to support both U.S. and ultimately commercial launch. But you know, tariffs are a lot of noise out there, as you noted, and this product's made in Massachusetts. Vorolanib, which is our key API, is also made here in the United States, so our tariff exposure is low, if not zero. Okay, great. Maybe we can turn back to the phase III and what you've seen so far. Any updates on safety and discontinuations? We reported at the end of Q2 that our data safety monitoring committee met, recommended no changes, and to proceed as planned. So as you know, both trials are enrolled. We are now actively at the point in time where there's redosing going on, and you know, our safety, as we last heard, has just been fine, and it's not a surprise to us. To remind the audience, through phase two, we've DURAVYU has been in over 190 patients, no ocular or systemic SAEs, and vorolanib itself, we know, has great ocular safety profile as well. So our safety remains superb. We have no PEG, we have no PLGA, and you know, the profile, you know, so far, so good, and but not really a surprise to us. You're talking about safety, like, since the last update. That now includes redosed patients? I would say when the DSMB met, and again, I'm gonna have to defer to our clinical team, there may have been some redosing, but some redosing has certainly occurred in the last few months. You know, I would say no news is good news, but we're not surprised. Okay, and how, or when can we expect our next safety update? So the committee meets every six months. I think the next meeting is in November. And so we will certainly give an update after that. And we'll, you know, continue on our execution on the clinical trials. All right, and then timing of the phase III data? So LUGANO was fully enrolled in May. It's a 56-week endpoint. We're blending 52 and 56 weeks because that's the right thing to do, and FDA suggests it, and it de-risks your trial, and so that data will be available, call it next July, August, and LUCIA, you know, roughly two months behind that. So hopefully by the end of Q3 next year, we'll have both trials reading out. We expect to report LUGANO first and then LUCIA. The nice thing about our trial design is both trials are identical, so LUGANO will inform LUCIA. It's also going to allow us to start writing our NDA quickly, and then we just drop the LUCIA data set in. So it's gonna give us a good pathway to get that NDA filing accelerated. You said safety updates, meetings every six months. The next meeting is in November. Could we see an additional safety update ahead of the top line? Let's see. Yeah, I think so. But, you know, by then, you know- It'll be right around the corner. Should be, yeah. What other updates ahead of the top-line data can we expect? So we've got a number of publications really related to DME and some of the subset analysis in DAVIO 2. In Retina Society in two weeks, we've got additional color on the DME trial. I suspect early next year we will be sharing some of the patient demographics across the phase IIIs. I think the team's working through LUCIA now to make sure we have all of that validated and all the boxes checked, and we'll share that likely early next year. Okay, and since you brought up DME, you're coming off the back of a positive end of phase II meeting. Any tidbits you can give from that meeting? And just in general, I know wet AMD is the focus, but how is the team thinking about the DME opportunity relative to wet AMD? Yes, so, it's an interesting dilemma for us at EyePoint. Just to remind the audience, our DME data we reported in the first quarter was remarkable. We showed an immediate and sustained effect in both improvement in vision and reduction in fluid, and we maintained that for six months, essentially with just our drug alone. The retina community is very excited about this data. In fact, you know, anecdotally, we were just at ASRS in July, and had doctors stopping us in the hallway asking to be in the trial, which technically doesn't exist yet, so a lot of really great enthusiasm in the community for this trial. If you think about the DME, which is diabetic macular edema, that community is not the best at compliance, and the concept of having an every six-month drug where patients go home with forced compliance is really resonating. We met with FDA in July, had a very positive end-of-phase II meeting, got alignment with them on the protocol, on the N. I think importantly on the N, it's gonna be meaningfully smaller than the wet AMD trial simply because we'll already have established safety. You know, if you look at the DME program, we could have done it with a much smaller N, but we wanted the right N for safety because we wanted to make sure we had that 300 patients for redosing every six months. So the N will be smaller, and then we're working through the final protocol design internally, and we'll come back to the street later this fall. At the end of the day, DME is a 2026 event for first patient dosing. We're very excited about this program, but as you note, it's all about wet AMD, and we like to think we're a big company, but we're not a big company yet, and we are keeping everyone focused on wet AMD. And in one of our meetings today, someone, you know, suggested, "Yo, you're on cruise control now," and I kind of wish that was true, but the reality is, we've, you know, our clinical team is focused on, you know, trial integrity, data integrity. Our manufacturing team is really working to make our process robust, and so we don't want to take our eye off that ball, but it's not lost on us that DME is a real opportunity. It's the second-largest market behind wet AMD. Our data was just spectacular, and we think it's a real opportunity, and so we'll bring an update later this year for that. If first patients in 2026, can you say first half or second half, or TBC? Can you just give me the year for now, and let's hope it's first half. Okay, and then once you get that started, how quickly can you get it moving? Like, you said the N is presumably smaller, but I imagine enrollment dynamics are also a bit different from wet AMD. So here, here's the beautiful thing. We as we started this conversation, we broke records in wet AMD enrollment because we have an amazing clinical team. We have our CRO, and CROs get a lot of noise out there. Our CRO has done a great job, and we've got about 200 sites worldwide that would love to bring a DME trial. It's essentially all the same doctors. And so there's a lot of synergy that we're gonna be able to tap into to rapidly enroll that program, we hope, when that time comes. Okay, maybe a broader question. Just looking at the wet AMD market overall, it's a very active late-stage pipeline, which makes sense given the opportunity size, $14 billion-$15 billion market, $9 billion of $10 billion, which is from wet AMD. I think I've counted at least nine pivotal trial readouts between now through 2027, five of those in 2026. Two of those are your own. I guess given the landscape, what would you say sets DURAVYU apart from the approved therapies as well as other late-stage programs, and what are you hoping ultimately to... Where do you hope this therapy will fit? Great question, and thank you for asking that. So we've said all along that we are not another anti-VEGF. And if you look at our trial design, and I touched on this earlier, DURAVYU is a new mechanism of action. We are a receptor binding, we block all VEGF receptors, we block PDGF, we work intracellularly. Very different mechanism of action than all of the biologics that are out there. And, going back to our trial design, we expect our label to be something along the lines of, "Use every six months after three doses of an anti-VEGF." And so the doctors will certainly figure that out, and our commercial team is working on how we position that. But remember, this is really the first new... Wet AMD broadly is the only major category with one treatment MOA. We're gonna hopefully bring a second to that. And if you look at other major categories, you know, diseases get treated and reimbursed with multiple MOAs everywhere, including glaucoma, as an example. And so, our position to doctors is, this is very simple: get your patient, you know, stable. And we get the question all the time, "Well, what about biosimilars? What about gene therapies?" We're agnostic. They're all the same MOA. Get your patient stable, put in DURAVYU. If our phase II data holds, we're gonna take two-thirds of your patients six months or longer. You're gonna get that second MOA on board, constant drug release, and you're gonna have, at a minimum, a sense of security knowing there's always drug on board because these patients are elderly, they miss visits, they move, they go to Florida, and so we think we're gonna be in a really good position there. And you made the other joke that physicians never read the labels in real, real world use. Just ask them. I guess another joke is duration of approved therapies and how to think about what the approved therapies are approving, or getting to in terms of duration, and how meaningful is an incremental improvement in duration in terms of commercial success? Yeah, so, you know, so duration comes up all the time, and if you simply look at DURAVYU as durable only, you know, what we can do that none of the biologics can do is last six months or longer. You know, despite recent, you know, headlines, the reality is biologics just don't last that long in the eye. It's biology. And so, VABYSMO is a great recent example, where it's got this promise of more sustained delivery. It's become a $4 billion drug in two and a half years. But if you look at data in real world, and there was a ASRS a year ago, they had done a, I think it was RCA, had done this internal study on their VABYSMO patients, how much longer they lasted than Eylea patients, and it was only one to two weeks longer. Despite that, they've grabbed a great market share. If you talk to retinal practices, the reality is these practices are swimming with patients. They're injecting 70x, 80 x a day, and they need to get some of them out in duration. On the simple basis of duration, we think we're gonna have a significant market, and then add in new MOA, potential neuroprotection, potential anti-fibrosis. I think they'll, you know, with the right data, there'll be a lot of arguments to use our drug on everyone. Now, there is one phase III trial that will be reading out before your trials in the first quarter of next year. How would you characterize the potential read-throughs from that program? So they're both TKI programs, and so, you know, whether other company likes it or not, we're tied at the hip and I think both companies have shown that TKIs work in this space. I think if you look in wet AMD broadly, TKIs in about seven trials have worked. And so, you know, they, I know their trial design is unique, and they're certainly gonna be read through to us, but it's a very different trial than we're running. And so, you know, we'll be prepared to talk about that. But remember, Jennifer, we did a phase II. We have real data across several indications that we can point to that show that our drug works, and I think our phase III design is very straightforward. It's non-inferior, which is every drug since LUCENTIS has been approved under that same pathway. There is one data set before us, but then ours are coming in short order shortly right after. And just remind us, how you're thinking about the timing to launch and how comfortable you are that you're in the lead here? So just based on disclosed math, we're very comfortable that we're gonna be first to read out both phase III trials. As a result of that, we'll be first to file the NDA and first to commercial launch, just based on public statements by our competitors. And again, coming back to LUGANO, LUCIA, they're the same trial. So LUGANO's gonna inform you very meaningfully what LUCIA should do. And you know, as a result of that, it puts us in a good position to get our NDA filed quickly. Okay, last question, since you are the CFO, remind us what your balance sheet looks like and maybe give a outlook on key catalysts over the next 12-18 months. Yeah. So we're, we have done a great job, and I give the whole EyePoint team credit. We are great stewards of cash. Our cash guidance has remained unchanged for the last year. We ended Q2 with $256 million. Our cash guidance is into 2027, which is about 9 to 12 months of cash on the other side of data. That's been unchanged, and what's really fascinating about that is, our burn was substantial in the first half of this year, but it was for all of the right reasons, because our trials enrolled so quickly. We pulled spending in from 2026 into 2025 because it went so well, but our cash guidance is unchanged, so we're gonna continue to be good at execution and good on managing our cash and looking forward to data next year. It's gonna be an exciting year. George, thanks so much for being here. Thank you very much.