My name is Yatin Suneja. I'm one of the Biotech Analyst here at Guggenheim. Welcome to our sixth annual Biotechnology Conference. Our next presenting company is EyePoint, and from, from the company, we have Chief Financial Officer, George Elston. George, could you maybe give us sort of an update on where you are? What are some of the next milestones? Obviously, there is new data coming up, but there is a lot going on at the company, and then I'll ask some questions that I have prepared for you. Sure, and thanks, Yatin, and thank you for having us here at the Guggenheim Conference. We're very happy to give an update. I think it, you know, coming off the heels of a really incredible 2023 for EyePoint, where we had very positive top-line data in our DAVIO 2 trial in wet AMD, that allowed us to subsequently raise a $230 million financing, and we ended the year with $330 million of cash. I think what's important about that is we've we're now in a position to execute on our phase III trials, and we can get we'll get into the DAVIO 2 a little bit. But the DAVIO 2 results, the statistics of that trial, were so tight with that we hit statistical significance to a 95% interval. I'm sorry, 95% confidence interval with 160 patients. So what that means is our phase IIIs are now much more manageable, and with the financing that we've done, it's put us in a position now to be able to fund those trials on our own. And so it's changed our partnering discussions in the sense that we are now taking that program forward through phase III, under the EyePoint umbrella, and looking forward to move on beyond that. We expect those phase III trials to start second half of this year. More near term is we do have the PAVIA trial reading out in Q2. To remind everyone, the PAVIA trial is EYP-1901 in the non-proliferative diabetic retinopathy indication. That trial is two arms against a sham control, and we're looking at a nine-month endpoint, and it's a two-step reduction in the DRSS score. We're particularly excited about that indication. That non-proliferative diabetic retinopathy indication right now has very little uptake of anti-VEGF because of the injection burden, and we think if we can provide a therapeutic option that matches the cadence of that patient visit to their doctor annually presents a very significant market opportunity for us. And then the third indication for EYP-1901 is in diabetic macular edema. We initiated that trial in January. That's a small 25-patient trial with two doses against an aflibercept control. We expect that to read out in Q1 of next year, and the concept of the DME trial is really twofold: number one, to get experience in that DME population as we think about what a pivotal might look like for that indication. We've strategically placed that third in the cadence. FDA guidance to us on EYP-1901 and clinical trials is what we need to do, two pivotal trials for the first two indication, and then there's the potential for a single, pivotal trial subsequent to that, for each follow-on indication. So, DME as a third indication makes sense under that protocol. Got it. Okay, very good. So maybe starting with DAVIO 2, obviously, very good data. I think Street finally caught up to it now or getting where they should be. What are the next step? Like, what elements you need to get a buy-in from the FDA before you start the study? You mentioned, you know, you hit the stats very successfully with 160 patient, but there is this safety requirement, right? That requires a bigger phase III program to be run. So I'm just curious to understand this, if you can articulate for us the size and the scope of phase III and the key elements that you need to discuss with the FDA around it. Sure. So, I think most importantly, we are... Just to bring everyone back, after the DAVIO 1, the phase I trial, we actually went to FDA because we were, at the time, contemplating doing a straight to pivotal. And so we went to them with a stats package and a protocol for a phase III design, and we did that under a Type C meeting- Mm-hmm. Which we had minuted. That's your traditional non-inferiority trial, which is the pathway we're pursuing. We ultimately decided to do the phase II trials, which read out in December. So for the phase III, you know, the plan is to go into an end of phase II meeting with FDA sometime around the end of March. We're completing the briefing book as we speak, and using our Type C minutes under a non-inferiority trial design. DAVIO, the phase III for wet AMD, should look a lot like the DAVIO 2 trial, with a couple of exceptions. Number one is, we plan on redosing. Yeah. We will be redosing EYP-1901 every six months, so for a total of four doses over that two-year trial. We will be submitting 12-month data, so with the endpoint is 12 months for FDA, so we'll be submitting a 12-month package for safety and efficacy, and the plan will be to follow on with the 24-month data. Mm-hmm. On the end of the trial, and that's really been the, you know, the interesting discussion, and we're still working through that, and that'll be part of our end of phase II meeting, is to really identify, you know, what is the end of the trial. We're going to power it properly to get the readout, and I think what DAVIO 2 gave us is, you know, we're no longer powering the study for statistics. It's really about sizing it for safety. Yeah. And there is a 400-patient number that the FDA put out there, that they wanna see safety in 400 patients at your go-to-market dose. So we have that as a target, as part of the trial design. But, you know, if you look back at the DAVIO 2 data, we really didn't see a dose response between the 2 mg and the 3 mg insert. And so our current plan for phase III is we're gonna go forward with two different doses, but it's gonna be two inserts and one insert. And there's the concept, and we're still working through this, but there is a potential that the single insert may be just as efficacious, and we wanna make sure we test that in phase III as well. Yeah. So that's gonna push some of the N a little bit higher, but certainly within the scope of our financing. Okay. So lower dose, one lower dose, that you're gonna take. We have not seen any redosing data, so what gives you comfort that the redosing doesn't introduce any new risk or, you know, or those risks are manageable, mostly around safety? Yeah. So I think, you know, we're to date with both, DAVIO 2, DAVIO 1, and even PAVIA today, you know, the safety for 1901 has really been- Yeah ... spectacular. We haven't seen any 1901, no SAEs related to, ocular or systemic SAEs related to 1901, and so we're getting increased confidence, with this program. On redosing, we've completed all of the required tox redosing, and the FDA has seen that. We haven't yet reached a maximum tolerated dose or number of inserts in animals. Uh. Just to remind everyone, we're using the Durasert, Durasert technology, which has been in tens of thousands of eyes, as in the non-erodible formulation. So we bring that safety history into this program as well. Yes, we haven't, you know, this will be the first time we're redosing- Yeah ... EYP-1901 in humans, but there is some history with the prior products, YUTIQ and ILUVIEN, where those have been redosed, and there's not been any issue. So, you know, you don't know until you're there, but, you know, going into the trial, you know, based on the animal data and based on the history of the technology, we're feeling pretty positive about that safety. Got it. Any changes in the patient population relative to DAVIO, DAVIO 2 for the phase III program? So, to be determined, I think where we sit today, we're still parsing through the DAVIO 2 data, but I think where we sit today, those results were pretty spectacular. There may be some minor tweaking on the inclusion/exclusion criteria, but I think where we sit today, it's going to largely be the same trial. Got it. I think you recently presented, actually it was last weekend or this past weekend, you presented new data or new subgroup data. Any key learning from the new data that you're presenting that's worth sort of highlighting? Yeah. So, at Angiogenesis this past weekend, Dr. Carl Regillo presented a subgroup analysis of the patients in the clinical trial that went 6 months without a supplement. And, the data was pretty spectacular. Essentially, what it showed was that the 1901 arms did better than the Eylea control out through 6 months. We were numerically superior after just a single injection. And if you look at the OCT chart, the OCTs were very stable, you know- Yeah ... right through six months. That was, that was really powerful data. You know, we, we've talked in the past about the potential for neuroprotection in 1901. Yeah. I don't think this necessarily signals that, but it certainly leans in that direction. And what's interesting about that is, you know, some of the comments or, you know, questions that we've gotten as well, "Is your visual outcomes driven because patients are getting supplements? Supplements. Actually, it's the opposite. We had better visual outcomes without supplements with our drug. So it's certainly KOLs and investigators are very intrigued by that data- Mm-hmm. We'll learn more as we continue with the DAVIO 2 analysis. So, in other words, the outcome of patients that got the supplement were no different than the patient who did not get it. So basically, the guys who were getting supplement were not driving the efficacy. Correct. It was very consistent with- Right. - uh, So the subgroup were the patients that did not receive a supplement, and their visual outcomes at six months were better- Okay ... than Eylea, Q eight-week dosing. Mm-hmm. Supplements were not driving the visual benefit in the- Okay ... in the treated arms. Okay. Correct. So, you meet with the FDA, I think in, you know, in a couple of months, right? End of March is our timeline. End of March- Yeah ... April is when you meet. Then the second half, you start the study. What about timeline? Like, how quickly or what are the timelines around completing these studies? Yeah, so the current plan for DAVIO for wet AMD- Yeah ... and the trials, you know, it's DAVIO 3 as the broad umbrella. We haven't named the trials yet, publicly. But, the plan is to start the US trial in the second half of this year and have the OUS trial start several months later. As I mentioned, you know, we're gonna take forward 2 doses- Yeah ... plus aflibercept. It's gonna look very much like, Yeah ... DAVIO 2. You know, I think it's all gonna be based on how quickly when we can recruit. I think what we like about going into phase 3 is we had 70 sites in DAVIO 2. We have a lot of investigators experienced with the protocol and- Yeah ... with the product, and so I'm sure we won't use all 70 sites, but we're gonna have a good basis to really get the program kicked off. They're still actively involved with the 12-month readout for DAVIO 2. Yeah. And then, OUS, will start quickly thereafter. I think what's been very nice and just having recently been- Yeah ... in Hawaii Eye and the Angiogenesis virtual meeting this weekend, is there's a lot of interest in this program and these durable programs. So from a timeline perspective, you know, our-- we're thinking that the top-line data should be somewhere in mid-2026 for both phase IIIs. For both? Yeah. Okay, so that's on the AMD side. Any comment on the competitor? I mean, I think there was some interesting gene therapy data that was announced also over the weekend. Could that have any implications to you, and what are you hearing from the physician as we see the broader adoption of these high-dose Eylea or Vabysmo from a commercial dynamics perspective? Yeah, so really two different things there. I think on the gene therapy, you know, there, that's a very different class than we're sitting today. I think gene therapies are positioned as a one and done. Yeah. The data we've seen to date isn't really showing that. I think within wet AMD, we like where we're positioned as a six-month treatment. You know, as we think about commercial adoption and things like that. Mm. I think what is positive about what's going on with the gene therapy is it's showing that this pan VEGF inhibition works, at least on BCVA. Mm supports what we're pursuing with our program. You know, on the marketplace, on HD Eylea, Vabysmo, remember, as we think about 1901 within wet AMD, we're positioning it as a maintenance therapy. Mm. It's very different than how the wet AMD products have been evaluated in the past. In the past, you know, one product lasted slightly longer than the prior product. Our value proposition to physicians is: get your patient treated, pick your VEGF inhibitor, your ligand blocker of choice, get them stable. Put in 1901. If DAVIO 2 data holds, we're gonna take two-thirds or more of your patients out six months or longer and keep them dry without needing supplemental injection. So it's a very different position as a maintenance therapy, working in conjunction with the current anti-VEGFs. We're not looking to compete upfront with that very crowded refrigerator. In fact, we're a room temperature product, so, you know, physically and, you know, theoretically, we're not competing with them. Okay. Very good. Okay, so, moving on to PAVIA study that's gonna read out, what is the bar there? I mean, I've heard Jay talking about, you know, percentages like 30%-40%, but when we look at the VEGF data, at least on DRS endpoint, I think you're somewhere out there in the 40%-50%. So what are you planning to show? What is the bar? And, yeah, when exactly are we gonna get the data? Yeah. So, that's a great question, and I think, you know- Mm ... the NPDR space is very different. Just to bring everyone back to when we were evaluating... We call it the floor. Like, what's our minimum requirements? Mm to move forward? We had that for wet AMD, and fortunately, we really knocked it out of the park with all of those results. Yeah. NPDR is a little bit different. And you're right, if you look back at, you know, the Eylea and Lucentis trials, they were getting about a 40%-50% reduction in DRSS. The issue that they have and that that marketplace has is you have to come in monthly for that. Mm. In our discussion with KOLs, you know, they're telling us: If you're 30%-35%, we would use you because it's a every nine-month treatment, is what we're targeting. So we think there's room. And so it's, from our perspective, the floor is that 30%-35%. We certainly hope to do better. Yeah. As you think about where this product could potentially sit within that treatment paradigm, in giving the doctors a nine-month option, I think, you know, some of the feedback we've heard from KOLs is, you know, that we might be able to move forward at a lower threshold. At a lower threshold. So you're not necessarily targeting... So 30, 35 is the floor. Anything else, from, for us to look at here? What about OCT here? You know, so certainly, safety continues to be first and foremost. Mm. You know, there's a lot of focus on safety in ophthalmology. We are very pleased with 1901's performance so far, certainly in DAVIO 2 and in PAVIA. No drug-related, no 1901-related ocular or systemic SAEs. So we're obviously gonna look at safety, and, you know, some of those secondary endpoints- Yeah will be important. I'm not sure we're ready to rank those until we get that data. Yeah. you know, we are expecting the PAVIA readout in sometime in Q2 this year. Q2. What is the regulatory bar here? I mean, would you be allowed to run a placebo-controlled study here? Our understanding so far is yes, because right now the standard of care is observation. Mm. You know, we haven't had that direct conversation, but it appears that that is still an acceptable arm, is the control, the sham arm. You know, we obviously will take that up with FDA at an end-of-phase II. But you know, our current plan and timeline for that is, you know, that it would be - we would be able to move forward under that same protocol. Yeah. But this will be sort of a second indication, not necessarily leapfrog wet AMD, given, even though there is a lower bar here because you're looking at placebo, more patients. Yeah. So they're very-- They're on their own- Yeah clinical trial pathway. Remember, it's a nine-month endpoint. Mm-hmm. It's gonna take a little bit longer to accrue, and, you know, the reading takes a little bit longer. So to measure DRSS and two-step reduction is the FDA endpoint. But you're reading at the beginning and at the end of the trial, so it does take time. Okay ... to work through that. Okay. How big is this opportunity, let's say, relative to wet AMD? So, I think in the short version is, wet AMD is a massive market opportunity- Yes ... as we all know. What's interesting about NPDR, we think it's a market that doesn't exist today. Mm. Right? So if you look at Eylea and Lucentis, they are, you know, less than 3% of the market share because of the dosing burden. We think if we can truly provide a sustained zero-order kinetic product to doctors that matches the cadence of their patient coming in once a year- Yeah ... and they're sitting in the chair, and they can say, "I can treat you, and you'll be good for, you know, until your next visit"- Yeah ... there's a potential to open up a market that doesn't exist today. Got it. Got it. What about the DME? Okay, so that's good on the NPDR. What about DME? What is the status of the DME study? So DME trial- The going ... in, with 1901 is the VERONA trial. Yeah. We initiated that in January. We've dosed the first patient. It's a smaller 25-patient trial, two arms of 1901 against aflibercept control, and we're basically dosing everyone on day one and watching them for 6 months and looking at time to rescue. The concept of this trial is it will be our third indication- Yes ... with 1901. It's number one, to get experience in this patient population. And, you know, and we've strategically positioned DME third, under this notion that, you know, we may only have to do a single pivotal trial, for that indication. Same is true for NPDR, single pivotal? NPDR will be 2. Oh, that's true. In the U.S. Yeah. I see. Placebo-controlled, nine-month endpoint. Okay. Okay, that's that. I wanted to touch also on the, on your thinking around partnerships. So I think you, in your initial comment, you mentioned that because these data and how robust they are, you have the capital, it has changed your discussion with partners. So where are those discussions? Like, how are you thinking from a partnership perspective? You know, are you interested in a regional or global? Maybe help us understand where you are. Yeah. So, you know, just to refresh, so because of the very robust DAVIO 2 data and the tight statistics and very nice financing that we did, we are in a position to fund Phase III, and that's been our message. I think last year we had a message that when we were looking at more daunting, you know, clinical trials and ex-US clinical trials, that a partner made a lot of sense, but that's really changed on the heels of DAVIO 2. And we're confident in our ability to execute on that between now and mid-2026. On partnering, so I think from a clinical perspective, we've really taken that off the table. We're not really looking to do an ex-US deal today. But that said, commercially, in the future, we, you know, for EyePoint to do an ex-US launch is a bit of a stretch from today, so we would certainly be interested in future commercial collaborations. Mm-hmm. I think, you know, where we sit today, our plan is to keep that value, you know, through phase III. Got it. How have your discussion been with the EMA? I mean, any buy-ins you need or any sort of big deviation from the FDA relative to FDA that needs to be addressed with them before you start the global studies? That's been in motion. Okay. So we have designed, really going back to DAVIO2, we designed the trial so that it would be acceptable both here in the U.S. and in the E.U. So the team is working through that now as we plan, you know, for the DAVIO, for the phase III trials. The second pivotal will be ex-U.S., including the E.U. and likely Japan, Latin America, China, and other places. But you will start the first study- In the U.S. Okay. Yep. So, but the European... Once you get the European, you'll start that second study? So we'll start the U.S. study. Yeah. And then the second, which would be the OUS study, will include EU and other countries. Okay. Okay, I think that's good. On the pipeline, 1902, the TIE-2, where is that program? When are you going to start hearing about it? Yeah. So, EYP-2301- Oh, that's... -which is our TIE-2 agonist. Very interesting molecule. So, this was previously known as AKB-9778. It's a TIE-2 agonist. It works on the VE-PTP pathway. Basically, it upregulates TIE-2 to which is associated with vascular stability. This molecule was studied by a company called Aerpio. It actually had very good anatomical control. It was delivered subQ. It didn't have the BCVA impact. We acquired those assets several years ago. We actually own a fairly robust set of molecules and IP around this TIE-2 pathway. Mm-hmm. The molecule is called razuprotafib. Mm-hmm. We've reformulated that into Durasert as a potential six-month sustained delivery treatment and looking to move that into preclinical testing this year for PK, tox, et cetera, and, you know, move forward for an IND. We haven't guided specifically on what indications are, but, you know, as you think about where this molecule may make sense is, you know, in partnership with a VEGF, the, maybe the extreme example is you, you look at a superiority trial with a VEGF, and if you can show improved visual outcomes, that's another potential blockbuster drug as well. Yeah. Multi-blockbuster, I would say- Yeah ... in AMD. Okay, very good. I think that's all I have. Maybe final question is on the financial health of the company. So you did raise the money. How is the burn rate, and how is that going to ramp up as we look into 2025 and 2026? Because you're going to be running these multiple phase III study and maybe expanding or going into pivotal with NPDR. Yeah. So our cash guidance is through top-line data in the wet AMD phase III, which is into 2026. But it also includes all of the ongoing phase II activities- Mm-hmm. for NPDR and DME. So we ended 2023 with $330 million of cash. We have no debt. We transacted our commercial business last year. So our burn is solely you know, largely focused on execution of clinical trials and, and R&D. And we feel very good about that. I think in the future, with outcomes in both NPDR trials and the DME trial next year, you know, that may be another catalyst for us to, you know, look at, you know, different types of financings. Financings. to fund those phase III as well. Very good, George. I think that's all I had for you. Great. Thank you for your time. Appreciate it again. Absolutely. Thanks, everyone.