All right. Good afternoon, everyone. Thanks for being with us for the Baird Global Healthcare Conference. My name is Colleen Kusy. I'm one of the biotech analysts here at Baird. I am pleased to have with us today, EyePoint Pharmaceuticals, including CFO George O. Elston. Thanks for being with us, George. So let's kick things off, if you wouldn't mind, with a brief overview of EyePoint. Sure, and we'll follow the slides along here. So just from a summary perspective, EyePoint Pharmaceuticals, we are focused on treating severe eye disorders, leveraging our Durasert technology, which has been in over 80,000 patient eyes in its non-erodible form. We are actively moving forward with EYP-1901, which is currently in two phase II clinical trials. The first in wet AMD, called the DAVIO 2 trial, and the second phase II is in non-proliferative diabetic retinopathy in a trial called PAVIA. The DAVIO 2 trial will read out in December of this year, and PAVIA, Q2 of 2024. We also plan on starting a DME trial in Q1 of next year with EYP-1901. EYP-1901 is a very exciting compound for us. It's leverages our bioerodible Durasert E technology with vorolanib, which is a very specific tyrosine kinase inhibitor. From a balance sheet perspective, we're in a really good place. We ended Q2 with over $142 million of cash. We have cash guidance into 2025, which includes funding all of our ongoing phase IIs and phase III preparation. So from a pipeline perspective, I did mention the two trials in wet AMD and NPDR, which are fully enrolled, and we're now on a glide path to that data readout. The DME trial will be a six-month endpoint that we'll initiate in Q1 of next year. This morning, we updated the Street with an 8-K filing with our investor presentation, so we've advanced into preclinical development. Our next pipeline program called EYP-2301, it's a TIE-2 activator. The precursor for this program was, we acquired the Aerpio assets several years ago. They had a molecule called AKB-9778 that was studied through phase II. That was a subcutaneous injection. We've since reformulated that, and we're going to look to advance that as a 6-month potential treatment for wet AMD and NPDR. So more to come on that. I think just one last point here on the pipeline is we are actively continuing to evaluate complement programs. We see geographic atrophy for sustained delivery as the next big opportunity for us, and more to follow on that next year. As I mentioned, you know, we're in a strong cash position. We did have debt. We exited our commercial business in May, so we did have a commercial franchise, including YUTIQ. We transacted that with Alimera back in May. We were—that was an $82.5 million transaction. We received $75 million upfront. We paid off our debt and sit in a very good place. And then, just from a key milestone and execution, I think if you look at EyePoint over the last 2+ years, we have a great track record of continued execution into clinical development. We've met or exceeded all of our guidance to the Street on our timelines, and as I mentioned earlier, we are well positioned to read out the DAVIO 2 data in December, which is our next key milestone, and, you know, continuing to move forward and keeping a great balance sheet. All right. Great. That's the, that's the overview. Thank you, thank you for that overview. Let's, let's hop into Q&A. So, you know, as we're approaching this really important catalyst, as you mentioned, DAVIO 2 data in December this year, let's just take a step back and touch on what the phase I data showed that got you excited about EYP-1901 and wet AMD. Yeah. So, what 1901 is, it's a tyrosine kinase inhibitor. We're advancing that as a potential maintenance therapy, so as a six-month sustained delivery option in wet AMD. The DAVIO 1 trial, what that demonstrated to us is we were able to take a majority of patients out six months or longer without requiring another supplemental treatment. And I think what's important about this program to remember is that, it's a tyrosine kinase inhibitor, so it's very different than the historical treatment in wet AMD. And if you look at high-dose Eylea, the Vabysmo, et cetera, and that with those large molecule ligand blockers, one product lasts a little bit longer than the prior one. We're coming at it from a very different perspective, a sort of a paradigm shift in that, you know, with it, with our TKI, we're able to block at the receptor level, and using our Durasert technology, we're able to give sustained zero order kinetics over six months. So what we saw in the DAVIO 1 trial was, number one, very good safety profile, and we actually updated safety this week, which we can come to on DAVIO 2. Continued to be a very good safety profile for this program. We were able to take a majority of patients six months or longer without needing a supplemental anti-VEGF treatment, and most importantly, we're able to meaningfully reduce the treatment burden, 75% at six months, and that's in an all-comer trial. So we didn't exclude for fluid, and we actually had three fairly high fluid eyes in that trial, and despite that, had, you know, very good outcome. Great. So you've shared the baseline characteristics for the DAVIO 2 study that's currently ongoing. How does that compare to the DAVIO 1 baseline characteristics, and what are some of the other differences to keep in mind when thinking about the two studies? Yeah. So I think that a couple of things. So on the baseline characteristics, which we released at last month at OIS, what was clear to us from the DAVIO 1 trial, despite having very good outcome, is there were three eyes that required supplemental treatment at one month, and that's basically five weeks after an EYLEA injection. And so not only did they not pass, that they, they failed our drug, but they failed standard of care. And when we did a deeper dive on that, it was pretty clear that, you know, they had very high intraretinal fluid around 400 microns. And so as an exclusion criteria for DAVIO 2, we put a 350-micron exclusion at screening. So they've gotten loading doses of EYLEA. So at screening, if you're still showing fluid, you're like a likely non-responder. We don't see that as a major impact on the label or the market, because that's only about 5% of the population. And so, when we published the baseline characteristics for the patients, you know, if you look at the average CST, which is a measurement of that fluid, in DAVIO 1, the average CST was about 299 microns, so fairly high fluid levels. In DAVIO 2, the average is about 265, which we believe is a much more representative and well-controlled population, largely matching the general population. So we'll see. Great. And you have, as you referenced, shared some masked safety data from the DAVIO 2 study. So maybe just walk us through what you've seen so far. Yeah. So earlier this year, we did announce interim data safety for DAVIO 2. No systemic or ocular SAEs associated with the drug, so continuing that strong safety profile for not only the Durasert technology but for this program. And then Monday, we updated that safety, so through September first, for DAVIO 2, that profile continues. No SAEs. We also added updated PAVIA, which is the non-proliferative diabetic retinopathy trial. All patients out three months in that trial with no SAEs, systemic or ocular. So we're feeling pretty confident about the safety profile for this program. I think importantly, when you look at diseases where you're injecting the eye, most of your SAEs are gonna happen in the first 30 days, and, you know, we're now feeling pretty comfortable that three months out, we're not seeing anything. Great. And so this will be the first time that we're seeing data for EYP-1901 versus a control of EYLEA. So I think the first primary endpoint that you're looking for here is BCVA, right? Yes. In the DAVIO 2. So kinda help us set the expectation on what you need to show on BCVA for this to be a positive study. Yeah, so, you know, the FDA has been very clear on what this is a non-inferiority trial, and so they're very clear. The primary endpoint is non-inferior BCVA versus Eylea on label. The standard that FDA has set is -4.5 letters. So that's kind of the far end of the bracket. As we think about change in BCVA, you really have to take that, you know, you certainly want to be 4.5 letters or better, or -4.5 letters or better, but you want to also measure that with reduction in treatment burden. We're really looking at both in parallel, because you can have, you can improve vision by a letter, but if you haven't changed BCVA. I'm sorry, if you haven't changed treatment burden, you know, you really don't have a path forward. You know, to us, and if you talk to KOLs on treatment burden, they'll tell you that 30%, they would love that. We, we're sort of lightly targeting 50% reduction in treatment burden, along with a non-inferior BCVA outcome. Great, and should we be expecting a statistically significant change in... or non-inferior margin to BCVA in this phase two? Yeah, so this trial is not powered for statistics. It's not powered as a pivotal, and the reason for that is, when we look at Phase III, we're really looking at re-injection and then a 1-year endpoint, and this is a 6-month endpoint with single injection. Got it. Will the standard deviation play any role in how you're analyzing these data? It's certainly going to be, you know, part of our statistical analysis and, you know, what standard deviation you use. I think, you know, the, you know, for the non-inferiority trials, if you look at the Port Delivery System, they used 7. So, you know, but, you know, we haven't guided specifically on what standard deviation we will or plan to be using. Understood. And so you referenced the reduction in treatment burden, and another metric that you've shown in the past is the rescue free rate. I guess kind of talk to us about, you know, is one of those more meaningful than the other, or what? What do you need to show in the rescue-free rate? Yeah, so again, rescue free kind of drives, the treatment burden, right? And so I think for both of those, you know, we're looking to have a meaningful, let's call it 50% reduction in treatment burden, and I think if we're at, you know, majority of patients out six months, you say 50%, for a supplement, you know, that's a good outcome. Great, and so- But I think you, again, you have to tailor that back to, you know, what's the overall reduction in treatment burden? I think what's... you have to be careful about when you look at DAVIO 2 versus DAVIO 1, this is a controlled trial where they're getting EYLEA on label, so the denominator is gonna be a little different, right? DAVIO 1, we're looking at retrospective, and they were about 4.2 rescues per 6 months. In DAVIO 2, they're getting at least 3. Actually, what's interesting about this trial, it may be the—we believe it's the first time you're seeing previously treated patients being restarted on 3-dose, you know, 3, 3 doses of EYLEA, and then on label. And so if you look at the literature, about 20% of patients can't go past monthly EYLEA, so don't be surprised if there are rescues in the control arm as well. Yeah, and that actually segues to my next question. What is the rescue criteria in this trial? I think it feels like the FDA... hasn't been totally clear on what sort of retreatment guidance- You know, they, they haven't been, because that's not, you know, from our understanding, it's not really what they look for approvable. I think it's the preponderance of data. If you look at the criteria for DAVIO 2, that we really drilled down on vision, because that's, with BCVA being the primary endpoint. And so, our criteria is a 5-letter loss with 75 microns of new fluid, and so that's a little bit tighter than DAVIO 1, which was a 10-letter loss and then 100 microns of new fluid at 2 consecutive visits. And the reason for that is we don't want physicians rescuing for fluid, because remember, we're giving constant dosing with 1901, and we actually had examples in DAVIO where patients showed a little fluid, and then it resolved. And so that's another criteria. Obviously, physician direct discretion is always available, and that's important in these trials, and then any new macular hemorrhage. Great, and so you're going to have a real wealth of data coming out of this phase II study. So how is this gonna help you design your phase III? Yeah, so, you know, we've had a Type C meeting with FDA 18 months ago, and, you know, if you look at the phase 2 design, when we met with them, we wanted to make sure that our phase 2 mimicked our phase 3. And interestingly, we had our meeting long before the draft guidance came out this spring, and we were quite happy to see that it was consistent with the guidance that we received. And so obviously, we'll be informed by the data in December, but right now we have a pathway to approval with our trial design. And again, the difference between DAVIO 2 and DAVIO 3, the pivotals, will be we're gonna do re-injection, and that's important because we want that on the label. It's a 12-month endpoint, and so that's gonna be the major difference between DAVIO 2 and DAVIO 3. Obviously, we'll be informed on what the readout is, but then, you know, we'll be in a very good position to make that decision. Got it. And so with redosing at six months, do you think that'll give you the type of flexible label that would, that would be beneficial to docs and patients? Yeah. So we've done quite a bit of market research and, you know, clearly, six months is a sweet spot for doctors. They're not gonna let their patients go a year without visiting them. Typically, with retinal specialists, if a patient's in the chair, they're gonna want to inject them. So as we think about the six-month label, it's it matches, you know, what they want to see. We know from our PK that our inserts deliver drug out through nine months, and we've already completed the tox work to show that, you know, we can have that overlap for the six-month dosing. So it certainly helps for the label and you know, also will help the patient and physician. Okay, great. And so assuming the DAVIO 2 data are supportive, how quickly could you start a pivotal study? So, you know, we have been in motion internally to gear up to start the phase III pivotals as early as second half of next year. Importantly, we control our destiny on manufacturing, so all of the inserts are made in our facility in Watertown. We are gearing up meaningfully to for phase III readiness and being able to have clinical trial material available to begin in the second half, you know, call it late fall next year. Great. Would you expect to meet with the FDA prior to starting the phase III? Yeah, the plan is to have an end of phase II meeting. Again, we've already had the Type C, but we're still gonna continue to, you know, have that outreach and be informed and certainly update them on the DAVIO 2 trial as well. Mm-hmm. Great. And so let's take a step back and maybe just talk about the wet AMD market. You know, there's a lot of approaches out there in development right now. Kind of how do you think your VEGF TKI insert is well positioned for uptake in this sort of market? No. And that's a great question, and we've really said from the beginning, you know, we're bringing a new MOA to this disease. If you look broadly at a lot of the disease categories, they're treated by more than one mechanism of action. Wet AMD isn't. All of those, you know, all of these large ligand blocker, anti-VEGFs, are basically targeting the same place. With our TKI, we're, you know, bringing a receptor binder, and we're bringing a new MOA. What we can do that none of the large VEGFs can do is go six months or longer. If you take the DAVIO 1 data, we were able to take a majority of patients out six months. So we've talked very openly about this treat to maintain concept, where you get your patient, you have a patient present, and you get them dry. You can pick your VEGF of choice. Those refrigerators are gonna get really full in those physicians offices with all of these new things coming in. And our concept is: Get your patient dry, put in a 1901. We're gonna bring you sustained delivery. We're gonna give you, you know, a new MOA, potential neuroprotection, 'cause we've shown some animal data. We'll continue to vet that in the clinical trials and be able to take a majority of patients out six months or longer. If you look at retinal specialist offices today, I mean, they're jammed. These doctors are injecting 100 times a day. There's just this wave of patients, and now with the new GA drugs there's just a capacity issue, and if we can provide this option, and maybe even some upside you know, we think we've got a very good position for that. Great, and 'cause—as you referenced, some of these drugs have started to go now every 4 months-ish, with Vabysmo and high-dose EYLEA, and you're looking, you know, 6, you know, maybe a little bit more than that. Is that kind of enough delta for docs and patients to want to use your drug relative to this evolving landscape? Yeah, and so we get that question often, and I think you sort of have to look back at this disease, right? And so the, you know, the way all of these drugs were marketed is, one drug lasted a little longer than the prior drug. We're seeing that with the more recent approvals. We're agnostic to which anti-VEGF you use. And if you look at the data, it's, you know, the studies were, you know, creatively designed, but I don't think in the real world you're gonna see those results. But regardless, you know, what we saw in DAVIO 1, and hopefully expect in the future, is patients that are well-maintained are gonna do really well on our drug. So, you can use your ligand blocker of choice and then use EYP-1901, and whether it's high-dose EYLEA or Vabysmo, we'll still be able to work in conjunction with that program. And I think the other thing to keep in mind, and, you know, we sort of have forced compliance with patients as well. Like, once the insert's in, it's delivering drug 24/7. In the real world, if a patient misses a visit, they're gonna lose vision. And so, you know, we think we've got that added benefit at a minimum, as an insurance policy. Great, and so in terms of reimbursement, would EYP-1901 be reimbursed any differently than the antibody approaches out there? No, we've started to do early work. Obviously, we're only in phase 2, but you know, I think it's very similar pathway to reimbursement as you think about. In In rough model terms, we would be no different than a 6-month course of EYLEA or another program. You know, instead of injecting monthly, we're gonna inject every six months, and there is some pharmacoeconomic benefit in between as well. Got it, and so shifting gears a little bit, you're also looking at EYP-1901 in non-proliferative diabetic retinopathy, as you mentioned. You also have shared some more safety data, as you men Yeah. Mentioned in the PAVIA study. What should we be thinking about? We'll see that initial data in 2Q of next year. How should we be thinking about that readout? Yeah, so we're excited about the NPDR indication. I think, as everyone knows, a lot of the large molecule ligand blockers are approved in NPDR, but they're not used. You have to look at that population to understand why. So wet AMD patients are largely older, they go into the retinal doc as part of their routine. If NPDR patients are younger, working age, and their disease progression, they're not really feeling it. And so to ask that group to come in monthly or every other month for an injection, they're, they're just not gonna do that, and that's evidenced by the current marketplace. Those, those drugs really aren't used for that indication. And if you look at our trial design, the control arm is observation. The concept for 1901 in this disease is, if we can match the cadence of patients visiting their doctor, you know, 9-12 months, where they're sitting in the chair, and the doctor says: "I know you don't feel your disease progressing, but it is. I can give you this injection and give you protection for the next 12 months." I think that will be a very compelling proposition. So that data is in Q2, and again, that trial is also fully enrolled. This is, you know, the data we released Monday on safety's first time of 1901 in a diabetic eye disease. You know, we're feeling, again, pretty good about the safety, and, you know, the clock has started for efficacy. Got it. And as you mentioned, a lot of these patients today are going untreated, partially because of the, the high burden of, of available treatments. But is there any data that you think you can generate that would really kind of try and convince patients to, to go on EYP-1901? Well, I think, you know, if the DAVIO data holds, and it's safe, and it's well-tolerated, and you give a patient an option to, you know, go from every month to every six months, I think that's gonna be pretty compelling. I think the other thing that we'll explore, you know, we did see some early signals of vision improvement in DAVIO 1, and again, small n. But I think if in DAVIO 2, we see a subset of patients whose vision improves, which is unexpected, that could be another compelling story as well. So again, we'll be informed by the data and look to... You know, I think at the end of the day, as we all know, data is, you know, what works in this space and we'll be able to use that forward. Great, in NPDR, after we have the initial data in 2Q, what would be the next steps from there? So we would, you know, look to quickly move to... Again, we'll be required to do two pivotal trials, in that indication as well, and the FDA has been very clear. You need two pivotal trials for each of your two first indications and potentially just one for your third, which in our case, would be the DME indication. So we would, on the heels of that data in Q2, we would again have an end-of-phase II meeting and then look to get those phase II, phase III pivotal studies started probably in 2025. We haven't really guided on that, but y ou know, the short math is somewhere in that range. Makes sense. So, let's touch briefly on DME. What would the strategy for development be? Would you run a similar design to PAVIA, or how would you move forward in that initiative? Yeah, so DME is a slightly different, disease, and actually, if you look, you know, every, every NPDR patient, you know, has DME, right? So we're doing this initial trial to explore, you know, how this drug's working in these patients. There's a lot of other options including steroids. So I think we'll be informed on the other side of that phase II on how we'll take the DME indication forward. Great, and let's touch a little bit on the TYRO3 asset that you just added to the deck this morning. How should we be thinking about that? You have, you know, a VEGF-TKI, and now you have, you're targeting TYRO3. For the same... It sounds like you're going after the same indication, so how do we kind of balance those two programs? Yeah, so again, this is a pipeline program, and, you know, the literature out there is, you know, fairly interesting, and if you look at Vabysmo, for example, you know, they're blocking VEGF, and they're blocking Ang2, which is the other side of this TIE-2 pathway. And so, Aerpio, who had this program previously, you know, had some pretty interesting data. You know, if you keep that TIE-2 pathway open, it's associated with vascular stability. And so you could see over time, you know, we haven't guided at all on, and nor will we, on what the indications will be or what the study designs will be, but, there is data out there to support that if you're suppressing VEGF and, and activating TIE-2, that you may have a better outcome. Okay. Would you look at this as a combination approach with VEGF, or would this be a standalone? We would likely advance it as a monotherapy, but in a maybe, but, you know, still more to follow there. You know, we do get the question, we have already gotten the question, will we put it with 1901? And the answer is not yet. We're not gonna advance two investigational products at the same time in the same disease, but you know, that's where we're going directionally. Got it. And, you know, on that point, though, is on the heels of our sale of YUTIQ earlier this year. We've really pivoted to being this pipeline story. EYP-2301 is sort of the next. We've been working on that program for a little while. Hopefully, we'll be talking about something in complement later next year as well. Great, and 'cause yeah, so touching on complement, you have a collaboration with Rallybio for their C5 inhibitor, coupled with your Durasert technology. So kind of just give us an update on how that collaboration is progressing. Yeah, so, you know, the guys at Rally know complement, and we continue. As a research collaboration, we're actively evaluating their C5 antibody and our Durasert technology and, you know, looking to find the right formulation to move forward. I think once we get to that point, we'll make an announcement and, you know, when it formally moves into a program. But we've, you know, it's still in research stage and, you know, stay tuned. What are some of the big hurdles when you're thinking about kind of further leveraging the Durasert technology to kind of make sure that the asset that you're putting in with the platform technology? Yeah, so if you look at Durasert historically, it does very well with small molecules. And so we, you know, there's a number of programs we're evaluating there. I think as we now are focused on building a pipeline, so, you know, inherited retinal disease and maybe some rare cancer. So there are some small molecule opportunities there. As the molecules get bigger and you think about sustained dosing, you know, you hit some limitations, and so we're evaluating. We do have other delivery technologies as we think about moving into larger molecules, and, you know, more to follow on that. You know, part of our strategic focus is to become a leader in, or, or I would say, stay and become a bigger leader in sustained delivery of drugs. And that, that's where our attention is gonna be. Great. And so, yeah, we've touched on a lot of different programs that you guys have going on, and you touched on the funding previously, but what's the funding strategy for the, for the phase III wet AMD trials? Yeah, that's a very fair question. So that data, you know, we've, we expect the DAVIO 2 data sometime in early December, plus or minus a few weeks. If you do the straight math, you know, we announced in March, last patient enrolled, so, you know, that last visit is sometime in November. Hopefully, they show up on time. And, you know, so give us a few weeks to sort through the data. And, you know, it's—we are in our cash guidance, it's... We're funding all, we're, includes all of our ongoing phase IIs and the, the phase III prep. But, you know, we would obviously need to top off cash to fund the trials. You know, we have a number of levers at our disposal. You know, hopefully, with good data, we'll be able to access all of them. We've had, and we've talked publicly about this, we've had great strategic interest. We've got a number of big strategics looking at us and for a potential ex-US partnership. I think our position is we are, you know, looking to build a company, and you know, we would obviously want to keep U.S., or at least participate in the U.S. So between strategics, equity markets, and, you know, there's other synthetics which may or may not make sense. But I think we'll be in a position come December to pull one or more of those levers. Okay, great. And so just as in these last few minutes here, as we wrap up, you know, sounds like a lot of interesting programs going on, and we're gonna see some data. So just kind of wrap up for investors why they should be paying attention to EyePoint in these next kind of 6-12 months. Yeah. So I think, you know, we have come a long way as a company, and if you go back to that chart I just showed you, we have a great history of executing and checking the box in our development, and we're gonna continue to do that. I think if you look at our near-term timeline, both trials have been, the enrollment's been completed. We know when approximately DAVIO 2 will read out in December. We've got PAVIA in Q2, and, you know, those are gonna be very meaningful events and, we're looking to build our pipeline. So I think as you look at the EyePoint story over time, you know, our, our goal is to have meaningful catalysts and continue to execute and show the Street that we do what we say we do, and we'll continue that. Fantastic. Very, very exciting story. Thank you for being with us, George. Thanks for having us. Really appreciate it.