Panelist here at RBC Capital Markets, and it is our great privilege to have EyePoint Pharmaceuticals joining us for a fireside chat. Representing the company, we have George Elston, Executive Vice President and Chief Financial Officer. George, thanks so much for joining us today. How are you doing? Thank you, Lisa. Thanks for having us. We appreciate the opportunity to be here at RBC and talk about the exciting progress we made at EyePoint. We are looking forward to the discussion. Excellent. George, maybe just to kick things off, would you like to give us a brief overview of the company and maybe tell us where things currently stand with the pivotal trials for wet AMD? Sure. EyePoint, at its core, we are focused on delivery of drugs to the back of the eye. We're a drug delivery company at heart, and we really are excited about our program, Duravyu, which is in two global phase III trials named LUGANO and LUCIA that are actively enrolling. We announced two weeks ago at earnings that LUGANO was over 90% enrolled. That trial started last October. LUCIA, over 50% enrolled. We're really thrilled with that progress. EyePoint's been a story about execution. We were just remarking recently, we dosed our first patient in our phase I in 2021, and here we are in two global phase IIIs. Our progress has been spectacular. We're well funded to get to our data point next year. Our guidance is complete enrollment in both trials second half of this year and data readout from both trials second half of 2026 with cash into 2027. We are really in a great place. Got it. Thanks for that, George. Maybe before we dive into the details of the pivotal studies, could you tell us maybe how your communications have been going with the FDA? You know, there's been a lot of changes there in recent weeks with workforce reductions and also the hiring of the new commissioner, Marty Makary. Yeah, so that's a really good question. There's a lot of discussion out there about FDA. I think, fortunately for EyePoint, and I think so far in the ophthalmology division, it's been business as usual. We've seen no disruptions. In fact, the agency has met or beat response times to us. We recently went to them with an end of phase II meeting book for our DME program and received all that communication on time and the end of phase II meeting scheduled for early July. All on time so far. Even our program manager and the team involved with DURAVYU is on tour. It's been business as usual. Got it. That is helpful. You know, I also want to touch on another macro point. You know, there has been a lot of discussion about the potential for pharmaceutical tariffs as well as conversations around most favored nation pricing. How is EyePoint kind of navigating all these almost like lightning-fast changes that are coming down from the government? Yeah, so it's been important for us at EyePoint. We feel we've been out ahead on this curve. For example, Duravyu is manufactured at our brand new state-of-the-art commercial facility in Massachusetts that was built to our specifications, and we can support global production out of that facility here in the United States. That team has done a remarkable job. We had our open, or I should say our ribbon cutting last fall. We're in the middle of registration batches. That team's laser-focused on not on completing registration batches and being prepared for pre-approval inspection. Vorolanib, which is our active API for DURAVYU, is manufactured in the US. We've really been out ahead of that curve to make sure we're in a good place there. I think from, you know, at least on the tariff side, I think most favored nations will see we are a couple of years away from hopefully a potential launch. That will certainly be part of our calculation. We've been very public that we will launch this product in the U.S. and bring in a partner for OUS. I think that will become a matter that we'll evaluate over the next few years. Got it. That's very helpful. Maybe let's talk about the wet AMD landscape. How is EyePoint thinking about this $15 billion market that's currently dominated by the anti-VEGFs? Where could DURAVYU fit in here? Yeah, so that, you know, thank you for that question. You know, I think importantly, DURAVYU is not another anti-VEGF. I think there's a lot of discussion, and I think that's been the dominant, you know, the anti-VEGF therapies have been the same treatment for the last 15 or so years for that disease. We bring something very new. We're bringing a new MOA. We're bringing a receptor binder, tyrosine kinase inhibitor that inhibits all isoforms of VEGF. We bind PDGF, which may have potential benefit on fibrosis. Even in our preclinical models, we showed potential neuroprotection. Our argument has always been that we are bringing something new. It's a new MOA. The history of the VEGF treatments is the newest treatment lasts a little bit longer than the prior. Use us, don't use them. Our argument has always been, use your VEGFs, get your patients stable, put in DURAVYU. If our phase II data holds, we'll be able to take two-thirds of patients or more six months or longer with just our drug. That's how we think about it. You know, we've positioned it as a maintenance therapy, second MOA, constant drug on board. We're not asking doctors to give up their VEGF. Use them with us, not instead of us. Got it. That's really helpful. You know, maybe one of the, and I'm glad you brought up how you think doctors are thinking about using DURAVYU. One of the biggest pushbacks I often hear from investors is that doctors are financially motivated to give patients as many injections as possible. Why should they switch to a longer-acting treatment if they're going to get paid less just because they're doing fewer injections? What are your thoughts on this argument? A lot of investors like to talk about that, but if you actually talk to doctors, it's very different. Doctors are always going to do the right thing for the patient. While, yes, I'm sure there are practices out there that love to inject, our argument to them is quite simple. We're not asking you to stop injecting except every six months instead of epiretinalizer, put in a DURAVYU. That's going to give you that constant background protection, two MOAs on board. It's, you know, it's practice dynamics. You know, we're not, the reality on the ground is most of these practices are jammed. They're looking for reasons. They're looking for duration. If you look at the success of Vabysmo, they're offering essentially eight days more, yet they've taken a massive market share. There is tremendous need within these practices to get more patients out on sustained duration therapies. And we've got a real nice opportunity here. George, you touched on fibrosis earlier. You know, the anti-VEGFs obviously have been very successful at keeping eyes dry. And we understand, you know, DURAVYU could help really solve patient compliance. One thing that does not get as much attention is the potential for sustained delivery treatment on fibrosis. Could you expand a little bit more on that? How could DURAVYU help there? I think we'll see this in the clinical data, but there's evidence out there that blocking PDGF is associated with fibrosis. The current anti-VEGFs do not block PDGF. I think we'll see in the data. The LUGANO-LUCIA trials are two-year trials. I think we'll have the opportunity to look at that at various time points when that data card flips at both the 12-month and then we will continue treating patients for 24 months. We'll see what kind of, that's to me, anti-fibrotic benefit is all upside. Certainly not on the pathway to approval. Got it. Let's talk about LUGANO-LUCIA. First, I want to touch on something else. You remind us about your global regulatory strategy. You kind of touched on it earlier. You're seeking to launch solo in the U.S., commercial ex-U.S. with a partner. How are you thinking about, you know, dealing with the FDA, dealing with the EMA, and dealing with other regulatory bodies? Yeah, so our regulatory team is, as you may know, both of our LUGANO-LUCIA trials are global trials. We have engaged broadly with regulatory authorities outside of the U.S. In fact, last week, we just learned from EMA that they've signed off on our clinical trials in Europe, which is a huge box check for us. We'll be looking to activate sites in the EU. We think that's a big hurdle. They are a bit of a tougher group to get through. I think it's good validation on our program, our CMC. Again, that's going to be helpful for a future partner. We will, we've been very public. We are not launching DURAVYU outside of the U.S. We will do that with a partner. Got it. Can you remind us, how did you come to choose every six-month dosing intervals for LUGANO-LUCIA? You know, the phase II, the DAVIO 2 study, the majority of patients, you know, did not need a supplemental injection at six months, but even nine months and 12 months. How did you settle on a biannual dosing regimen for the pivotal study? That's a really easy answer. That is, we asked often, what do you want? You know, these are high-touch patients. They're not going to let their patients go 12 months without seeing them. As we did our early evaluation on the program and the opportunity, six months was the sweet spot. Got it. Maybe just on enrollment, we already touched on it in your opening comments, but looking back at LUGANO, it looks like it took roughly four months to reach the halfway point of enrollment, but it has only taken two months to enroll another 160 patients or so and reach a 90% enrollment mark. A couple of questions on enrollment here. Is it within the realm of possibilities that LUGANO could actually complete enrollment in the first half of this year? If you do the straight math, absolutely. I think our guidance for both trials is second half of this year. We've been really excited and privileged on the robust patient and investigator enthusiasm for both programs. You know, we think we present to doctors and patients a great opportunity with this program. All patients are getting treated. We did a robust phase II trial. They are informed, and we're seeing that in the enrollment. I think it's beating not just historical records for enrollment in wet AMD trials, but even our own projection. The short answer is yes, but we're not changing our guidance at this point. The straight math certainly supports it. Got it. Maybe just on LUCIA, since this is over halfway enrolled, are you seeing an acceleration right now similar to what you saw in LUGANO once you reach that halfway mark? Are you getting even more patients joining the trial? We've seen pretty steady enrollment rates and screening rates, and our screen failure is actually doing better than we projected. We will have more international sites certainly in LUCIA. Again, we're seeing that same enthusiasm. One thing that we heard a lot about during Q1 earnings was that, you know, the underfunding of co-pay assistance organizations were really impacting patient access to wet AMD drugs. Maybe on the flip side, could this actually be a good thing for companies like EyePoint who are trying to enroll their clinical studies? Is that something that you've noticed? Yeah, so the short answer there is we did anticipate a drop-off in enrollment as the calendar flipped to 2025, and it was actually the opposite. We saw an acceleration in enrollment. While the Good Days program, which a lot of the companies have referenced being coming into this year unfunded, not great for patients, but it actually was very helpful for our enrollment. If you're thinking about your doctor, you have a patient in the chair, they're facing co-pays up to $400 per eye. The argument is, okay, you can go do your co-pays, or I can put you in this clinical trial where you're going to get standard of care and the potential for a sustained delivery option. Plus, we're also treating the fellow eye if it's available. It is a very easy discussion for doctors to have with patients. I think while that, unfortunately, that program was not good for patients overall, I think it was helpful for our following. Got it. Maybe let's just touch on, you know, the blinded supplemental injection rate. Is this something that you're tracking, and is this in line with your expectations? I'm sure someone is tracking. We at our executive level do not see that. Again, it is masked, so even if you do not know which arm they are going to be in. I think we are going to wait for the full data set before we take a look at that. I do not think it is going to be helpful to look at that soon. Got it. One thing I'm always curious about, you know, these are non-inferiority trial designs. These are kind of a tried and true path to approval. The primary endpoint is very well-defined, BCVA at 12 months, and non-inferiority is a four-and-a-half-letter delta between the treatment and the control arm. Has the FDA said anything about what they're looking for in terms of reduction in supplemental injections? That question has been lingering out there. We've had, in all of our interactions with the FDA, there's been no direct correspondence. Obviously, you know, supplemental injections is important. I think if you have a high supplement rate, you may not have a drug. Our phase II data was very supportive. We had a very low supplement rate. In our phase III, we've even narrowed our criteria very meaningfully for supplements because what we saw in the phase II trial, where we allowed investigator discretion, is about 20% of the supplements did not meet any criteria. Even deeper into that, when we looked at supplements, a lot of them had no effect on vision. In our phase III, we've really narrowed that supplement criteria to be very strict. That is five-letter loss with 75 microns of new fluid or vision-threatening hemorrhage. There's no investigator discretion. We do have a safety committee of peers that they can reach out to if they would like to supplement, all with the premise to minimize supplement rates and really focus on maintaining vision and visual function. Got it. Can you remind us, you know, EyePoint decided to pursue a new 2.7 mg dose and a new formulation in the phase IIIs versus the phase II, you had two doses, a 2 mg and a 3 mg. I guess what gives you confidence that the new dose will perform in the pivotals just as well as the results that we saw in DAVIO 2? Yeah, so I think first and foremost, same formulation, just a higher payload insert. Actually, if you go back over time, we've actually studied a 440 micron insert, a one-meg insert, now a 1.34 mg insert. In the phase III, it's two inserts, single injection, getting to 2.7 mg. If you look at the phase II data from DAVIO 2, there was essentially no difference between the 2 mg and 3 mg doses. We wanted to accomplish that with two versus three inserts, simple math, lower COGS, and it gets us from here to there. It's also a much smaller percentage of the matrix as well. We know that in about nine months, all of the drug is gone. We're essentially achieving that high dose that we saw in phase II with two inserts. Got it. And maybe just on redosing, you know, LUGANO-LUCIA, this is really the first time that you're going to be exploring redosing of DURAVYU on a larger scale. So what gives you confidence that redosing is going to be successful in terms of safety and efficacy in the pivotal study? Yeah, so great question. We are actually doing, in the phase IIIs, we're redosing every six months for two years. It will be a total of four doses. Why are we doing that? Because we want a label for every six-month dosing. We'll be submitting the NDA with 12 months safety and efficacy, and then supplementing that with the 24-month safety data. There's no non-inferiority margin for year two. We're very confident in the, at least in the preclinical work, we've done robust animal trials on dosing and redosing, and we've seen no dose-limiting tox for a number of inserts in animals. Very supportive of the agency seeing that and have signed off on our protocol. Got it. That's very helpful. EyePoint's also exploring DURAVYU in diabetic macular edema. George, can you explain to us the market opportunity here? Yeah, so in first quarter, we actually reported our 12-month DME data, which was really spectacular. We showed an immediate and sustained benefit of DURAVYU in DME patients. Like AMD, it's an exudative disease, and DURAVYU and Vorolanib seem to have a really robust effect there. What we saw was really remarkable. Essentially, at week four, we had immediate separation from the equilibrious epitarm. We had significant improvement in vision and associated significant reduction in fluid, and that was maintained through week 24. Doctors are very, and we've been talking about this earlier today. We've guided the street that DME will be a 2026 event. We've got the team laser-focused on wet AMD execution. We will have our end of phase II meeting with the agency in early July, lay out that plan for potentially a single trial, but that won't start until next year. The medical community has got a very different approach. They're very excited about the data and the program. Obviously, they want to see trials yesterday, but where we sit today and in these markets, we are, as a company, laser-focused on wet AMD. Got it. What other indications are you thinking you could explore with DURAVYU? I think our plan right now is to execute on these two, I mean, between wet AMD and DME, you're looking at two multi-billion dollar indications. I think with that data next year, we'll look to explore other potential indications. You know, a lot of the bed jobs are already here. We'll come back to, we'll update that later. Got it. Makes sense. Maybe let's just talk a little bit about potential commercialization of DURAVYU, maybe one on pricing. Obviously, a little bit early for this discussion, but from my conversations with investors, it appears most are modeling DURAVYU at a premium to the anti-VEGFs. Is that a fair assumption? Yeah, so I think if you just look at it, and again, at your point, it's early. If you look at it in simple terms of one DURAVYU replacing three, we've got six months versus every other month. There are some HEOR benefits as well. That could suggest a premium. I think if our phase III data supports potential neuroprotection, potential anti-fibrosis, then there's potential for premium above that. Again, it's very important. We see DURAVYU as not another anti-VEGF. This is its own new category in the space, and we'll be pursuing that commercial. Got it. How are you thinking about a potential launch? You made it pretty clear that in the U.S., you plan to launch solo, ex-U.S., seek a partner. What could a solo launch in the U.S. look like? Have you shared your thoughts on what you would need for a sales team, how many representatives you would need in the field, how many doctors, retina clinics you would need to approach? How should we think about that? Yeah, so what's unique about retina in the United States, at least, is that it's a pretty small footprint. There's about 2,400 retinal doctors in the U.S., and you could approach that with about 70 reps. Your commercial infrastructure is not that significant that you would need to invest in. We acknowledge there are two very well-funded, well-entrenched players, and marketing will certainly be a much bigger spend. Again, we are not directly competing with the vendors. We are not asking doctors to stop using. You may recall, EyePoint had a commercial product that we sold two years ago called YUTIQ, which was posterior uveitis. We've kept some key folks from our commercial team. They're doing a lot of this pre-commercial work. You know, we'll be gearing up to invest in that organization on the other side of data network. You know, we are not against having a global partner in the U.S., but I think right now we are full guns planning to launch this ourselves. Got it. And how should we think about, you know, the conversation that a sales rep might have with a physician? So they have doctors, they're on wet AMD, the physicians are very used to the anti-VEGFs. In the future, you'll have your phase III results, you'll have your label, you can discuss that freely. But how do you think the conversation is going to go about talking about maybe when to switch from an anti-VEGF on to DURAVYU? Yeah, so I think that you're, again, it's early days and for the record, not a sales rep. I suspect, and we talk broadly about an A to B shift. Again, we are not asking doctors to give up living. This is another MOA. You know, we've always talked about DURAVYU as a potential maintenance therapy. Get your patient stable. You look at our phase III design, we're doing three loading doses. Get your patient stable, put in DURAVYU. If our phase III, I'm sorry, our phase II data holds, we can take two-thirds or more patients six months. The discussion with doctors is we're not asking you to give up your red Jeffs. You know, in those cases, if you go back and look at value two, where a patient showed a little bit of fluid, it resolved, and they didn't need another treatment. There are other cases where they showed some fluid, they got an anti-VEGF, and they were fine for another six months. We are going to let data lead that discussion, but that is how we think about the market. Have you had any conversations with payers about, you know, potentially supporting a patient who needs the anti-VEGF and DURAVYU at the same time? If you look at the current market, right now, payers reimburse every 28-day injections of an anti-VEGF. We wouldn't look to disrupt that, at least from that perspective. We've had early discussions with payers. We've had early discussions with a lot of these practices and more to follow. I think what's interesting from the practice perspective is almost universally, their narrative is, "Don't slow us down." These are really active, robust practices where they're injecting 60, 70, 80 patients a day. The beauty of DURAVYU, we're shipped and stored at room temperature. We're not taking up refrigerator or freezer space, and it's delivered in a loaded injector, and it's going to fit right in the. Got it. George, I think that's all the time we have for today. Thanks so much for joining us, and we'll see you next time. Great. Thanks for having us. I appreciate the time. Thank you. Bye-bye.