Good evening, everyone. Thanks for being with us today for the Baird Global Healthcare Conference. My name is Colleen Kusy. I'm one of the senior analysts covering biotech here at Baird. It is my pleasure to have with me today EyePoint Pharmaceuticals, including George Elston, CFO. So George, for those who are maybe a little less familiar with EyePoint story, if you wanna start with a brief company overview, please.
Great. Thank you, Colleen, and really appreciate the opportunity, Baird provided us to be here with you today. I think EyePoint Pharmaceuticals is a very exciting story. We are a biopharmaceutical development company. We're about to enter phase III clinical trials with our lead program, DURAVYU, in wet macular degeneration. That's really on the heels of very positive phase II data in wet AMD at the end of last year, and it utilizes our Durasert delivery technology, which is a well-studied, well-known, very safe delivery technology that's been in tens of thousands of eyes, in previous four FDA-approved products, and we've actually evolved that technology to the bioerodible formulation that we call Durasert E, which we're using in DURAVYU, which is in clinical trials.
Fantastic! And yeah, so let's maybe start with the DAVIO 2 dataset. You know, you really do have a large phase II body of data to stand on here in wet AMD. So let's spend a couple minutes just kinda going over the highlights of what that DAVIO 2 data showed.
Sure. So the DAVIO 2 trial, we actually read that top-line data out back in December of last year, and that was a fairly robust, well-controlled trial. It was two doses of DURAVYU against aflibercept on label, and that's every other month, the aflibercept. In that trial, all patients got three loading doses, day one, month one, and month two, and then at the, at month two, thirty minutes after that third loading dose, they got one of two doses of DURAVYU or a sham injection of EYLEA. It was a six-month endpoint for that program, and what we showed in December is that we hit all primary and secondary endpoints.
We hit non-inferior BCVA with statistical significance to a 95% confidence interval, and we hit all secondary endpoints, including reduction in treatment burden, safety, which was really remarkable safety profile, and injection-free criteria. So really powerful data that inspired us to move forward into the phase III , which is coming.
Yeah
... near term.
Surely. Yeah, so let's dive into the phase III then. So kinda give us an overview of the phase II trial design.
Sure. So, you know, there's been a lot of discussion on phase III , and I think we've been very consistent as a company, really going back to our Type C meeting after our phase I . We spent a lot of time in front of FDA, and we met with them on the heels of our. Just a little bit of history on how we got here today. We had a Type C meeting after our phase I with FDA. The kind of early thinking was that we're gonna go right to phase III . We went to them with a statistics plan, a protocol, ultimately did the DAVIO 2 trial, which allowed us to be well-informed going into our end of phase II meeting that we held earlier this year.
So as a result of that, we are in alignment with FDA on our phase III , which, by the way, looks pretty consistent with what we've been talking about all along. It's a non-inferiority trial. It's one dose of DURAVYU. It's about a two point seven milligram insert. I'm sorry, two point seven milligram dose, which is two inserts.
... versus aflibercept on label. Two non-inferiority trials, the LUGANO and LUCIA trials, about 400 patients each, with a one-year endpoint. We're gonna be redosing DURAVYU every six months for the two-year trial. Year two is for safety, and we will submit the NDA with one-year data with the twelve-month endpoint, and then follow that with the two-year safety.
Great. And if we can touch on the status of your level of agreement with the FDA. I think there's a fair amount of noise in the market, somewhat around the use of sham, and just kinda how comfortable the FDA is with the trial design.
That continues to come up, and we're a little bit flabbergasted by that. FDA has been very consistent with us, and I think across the space. They are signed off on our use of sham for masking. It's been consistent with what they told us, and we are using that in our DURAVYU phase III trial. We're using aflibercept for control, so we're not using sham for control, we're using aflibercept.
Sham for masking, completely acceptable.
Understood. And so for this study, what do you need to show on the primary endpoint of BCVA? Is the, you know, exclusion of minus four and a half letters on the lower bound of the non-inferiority, or the, on the confidence interval enough? Or kinda what, what is the bar for-
Yeah, so that's the beauty of non-inferiority trials in wet AMD. You know, there is a defined non-inferiority margin, which is minus four and a half letters, and versus the aflibercept on label. You have to use aflibercept or Lucentis, because that's where the non-inferiority margin was derived, and well, that was part of our end-of-phase II discussion with FDA, so as you may recall, in DAVIO 2, you know, we were statistically non-inferior to EYLEA-
... and we had quite a ways to go to that lower bound of the non-inferiority margin.
Is there a threshold on rescue-free rates that you need to surpass? Or how does the rescue-free rate play into the FDA conversation?
Yeah, so FDA has actually not given any direct guidance on that, and I think at the end of the day, it's really about preponderance of data. You know, the primary approvable endpoint is change in BCVA, non-inferior change in BCVA. And I think, you know, our goal, and we had a very meaningful reduction in treatment burden in DAVIO 2 of about 80%.
... across two doses. So FDA has no specific guidance on it. I think it's, at the end of the day, it will be a review issue. You certainly want, you know, a high reduction in treatment burden, otherwise, you don't have an effect, and we had great data in phase II. And as we look at the phase III trial, you know, one thing we have included in our phase III design is our rescue or supplement criteria is really focused on vision. So it's a loss of five letters with seventy-five microns of new fluid, and that's the sole retreatment criteria or supplement criteria.
We've taken investigator discretion out of the phase III design, and, you know, if a patient meets criteria, they certainly can be supplemented, and there's vehicles with KOL advisors if an investigator wants, you know, feels the need to supplement. And part of that reason is we want to minimize supplements. Remember, we're DURAVYU is a different change in the treatment paradigm. You know, if you look at the current standard of care, doctors know with these large molecules, the drug's gone in four weeks. It's very different with DURAVYU. We're getting sustained zero order delivery for nine months, and so as we think about expanding this trial globally, you know, there's a muscle memory out there with doctors, and so we want to make sure that they're just not rescuing because they see fluid.
Because there's cases in DAVIO and DAVIO 2 where you see a little fluid, it doesn't impact vision, and it resolves the next month, and so we are really focused on that single rescue criteria, supplement criteria, and we'll look to control that in the phase III trial.
Great. And so one of the differences in this phase III design, you talked a little bit at your R&D day in June this year, is about the inclusion of treatment-naive patients, you know, which typically have a lot higher standard deviation on BCVA. So, why include those patients, and how do you expect that to change the stats of the study?
Yeah, so, you know, we look very closely at the DAVIO 2 results. And if you, if you look at, you know, DAVIO 2 as a whole, it was a very heavily treated population, and we did really well in that group. Included in DAVIO 2 are actually some we called pseudo-naive patients, where they were less than nine months of diagnosis, and DURAVYU did very well on those patients. We think that by including naive patients, we're gonna accomplish a number of things. Number one, it's gonna de-risk the trial for outcome. It's gonna expand our label.
And remember, and what's really important about the trial is, based on FDA mandate, we are doing three loading doses, and so by the time that any patient gets DURAVYU, they've already had three loading doses of it, so they're they're technically not truly naive, and we did very well with those patients in in DAVIO 2, and we think that's only gonna enhance our label in DAVIO in the phase III trials.
Okay. And will treatment-naive status be something you stratify for in your enrollment? And how do you make sure that there's kind of equal numbers of those patients?
Yeah, so I think there's a target for both treatment-naive and previously treated, and, you know, I think they're roughly half and half, so we're not gonna truly stratify, but there's gonna be some monitoring involved to make sure that, you know, we have a balance of patients in the trial.
How easy do you expect it will be to enroll the treatment-naive patients? And yet maybe you just answered this question, but kind of what percent of patients do you expect to enroll that are treatment naive?
So I think the rough target today is about half and half. If you talk to investigators, and I was a little surprised by this, they will tell you it's much easier to enroll treatment naive. We did really well enrolling previously treated patients, and if you think about the landscape, it's pretty easy to enroll tougher to treat patients because doctors are looking for something new, and I think as you get into these late-stage clinical trials, when a new patient presents, and what the benefit of DURAVYU is, we have a very robust phase II data set. So when doctor is sitting in front of the patient, they're able to talk to them about the results of DAVIO 2.
Our clinical protocol really matches the current treatment paradigm, so they know how the drug will be used, when and if they can be supplemented, and there's always an option for having treatment on board, and I think that'll transfer very well into recruitment.
Great. And talk to us a little bit about the dose selection for phase III , kind of why you chose the slightly higher dose, and I think you tweaked the drug amount per insert a bit.
Yes. So if you go back and look at DAVIO 2, we had a two mg dose and a three mg dose, so it's two inserts, three inserts. Each insert was about a milligram each. And if you look closely at the DAVIO 2 data, there really was not a dose response, especially in BCVA. You see a little bit potential improvement in CST with the higher dose, but really no difference in the dose response. In parallel with that, our manufacturing team continued to do process improvements, so we're able to develop a higher payload insert. So in the phase III trials, each insert is about one point three four milligrams-
per insert. So with two inserts, we're getting 2.7 milligram dose, which is close to that phase III . So we're certainly covering that phase, that 2 mg dose and a little bit closer to the phase III , and we're accomplishing it with two inserts, still a single injection.
And so does putting more drug in the insert get you a higher dose you're eluting per day, or do you think that gets you longer duration?
No, it's a great question. It's... You remember, our, the beauty of Durasert technologies, we're giving true zero-order kinetic delivery, and so while there's a little bit of burst upon initial injection, it levels off to zero-order kinetics for about nine months, so higher payload insert, you're getting a slightly higher dose per day.
Okay, great. And so you've said you'll start the phase III LUGANO study in the second half. So what are some of the gating factors between now and getting that study?
Yes, so, you know, we're here in September. We're in second half.
And, you know, the team has worked tirelessly, really since DAVIO 2 data at the end of last year. So we really have no gating factors. I think, you know, we learned a lot from DAVIO 2, and we in a couple of our meetings today, you know, when we announced first patient dose in DAVIO 2, it truly was first patient dose, one site, and it took us a while to get, you know, sites two, three, four, five up and running. We learned a lot from DAVIO 2, and in fact, we enrolled about 40% of that trial in the last three months.
We've since taken those learnings and really applied it to DAVIO 3. We've also brought in-house a new chief medical officer, who ran two very large global ophthalmology trials, and we are, you know, gearing up meaningfully. So when we announce first patient dose, you know, we have over 130 sites signed up already for our phase III s, and when we announce first patient dose, it's not one site, but it's gonna be kind of hit the ground running, you know, in a range of sites.
Great. And how quickly do you think you can enroll the first phase III ?
So that question came up in every meeting today. And, you know, I think we are, you know, as I said, we learned a lot from DAVIO 2. We enrolled that trial in about eight months. But remember, most of it was in the last three, and we're gonna take those learnings. We hope to... You know, if you look at wet AMD trials in general, they're sort of six to twelve months. We hope to be on the earlier side of that, sort of consistent with our guidance on data, which is, through top-line data in mid-2026-ish.
Mm-hmm. Great, and so since this study includes the three loading doses with EYLEA in patients who are both treatment naive and experienced, how do you foresee the label looking in terms of dosing requirements?
Yeah, I mean, you know, I'm not ready to talk about label negotiations today, but I wouldn't be surprised if that's on the label, but that's consistent with our positioning of DURAVYU as a maintenance therapy.
Right? And you know, it's a very complicated space out there today. You've got a number of anti-VEGF biologics, you know, approved or about to be approved between you know, the standard bearers, and now we have a range of biosimilars. And our message all along has been very, very straightforward, you know, to physicians: "Get your patients stable." You know, what we bring that none of these other programs bring is we're bringing a new mechanism of action. We can go six months or longer, which biologics cannot do, and so the concept is: get your patient dry, get them stable, put in our drug. If DAVIO 2 results hold, we're gonna be able to take a majority of patients six months or longer.
And so the concept, and even consistent with our clinical trial, you're getting those three loading doses, and you're gonna have a stable patient or as stable as they're gonna be.
Mm-hmm. I believe the randomization for the phase III happens prior to the EYLEA loading doses. I guess, did you consider randomizing after, and how do you think that might-
No, we randomize on day one, so once a patient's enrolled in the trial, they're enrolled in the trial.
So as we give updates over time, which we expect to do, and we don't really know what that cadence is. When we say we have X patients enrolled in a trial, they are randomized and enrolled in the trial.
I mean, how much variability do you expect to see in terms of the EYLEA induction period? And, you know, do you think you're able to sufficiently balance that prior to enrollment?
Between the mix of previously treated and naive? So if you look at the DAVIO 2 data, everyone in DAVIO 2, and that was a previously treated population, they all gained about a letter, and if you talk to physicians and patients, they really, you can't tell the difference in a letter.
I mean, that's and then everyone, pretty much, we kept everyone in our treatment arms pretty much the same. I think if you talk to KOLs and ask them the question: "After three loading doses, how many of your patients are not well controlled?" It's a low double digit, a low single-digit number. And so because we're randomizing the trial, even if you have that little bit of variability, it's gonna be spread between the two arms. And remember, we're doing non-inferior. We don't have to do better than EYLEA; we just have to be non-inferior versus that control.
Understood. And the second phase III study that you'll run, LUCIA, help us understand the timelines for that.
Yeah, so the beauty of having our clinical team and having our new—well, he's not new anymore—he's about seven months in, but he just came off running global trials. While, yes, it's really important to get your first patient dosed in your first trial, it's probably more important to get your last patient dosed in your second trial, and they're working on both. And so, you know, we are moving everything along in parallel, and so the focus is really getting those international sites identified. And we know what countries, what sites, and there's just as much focus on that as there is in getting the first patient.
Great. And so LUGANO will be all U.S., and LUCIA will be mostly international?
Yeah. The current plan is, so LUGANO will be largely a US study and potentially some Canadian sites. LUCIA is gonna be US and OUS-
Okay
... and including some international sites. But if you speak to our clinical team, I would say it's a competitive trial.
And so we're really gonna be looking to, you know, get that enrolled quickly and-
... incentivizing the sites to, or motivating the sites to do that as well.
Mm-hmm. And so what's been the physician feedback in terms of the initial trial design as you've laid it out?
It's been incredibly positive. You know, we were at our team is at Retina Society in Portugal today. We were at ASRS in Stockholm earlier this year. Both U.S. and ex-U.S. investigator enthusiasm is pretty palpable. You know, they've seen the DAVIO2 data. It's pretty remarkable. People want to be in the trial. We've again, I mentioned earlier, we're over 130 or so sites activated and really amazing interest. And so I think the team is geared up to hit the ground running, and you know, we hope that will continue.
Great.
We're very bullish on our ability to get this trial enrolled.
In terms of what you need to show in Europe to get approval, how does that differ versus the U.S.?
So we are engaged with our planning for Europe, but you know, where we sit today, we expect that our current clinical trial design will be acceptable in Europe and Latin America and other places.
Great. And taking a step back to kind of talk about the wet AMD market, you know, you're looking at a duration of about six months. You know, we've recently seen the market moving towards, you know, maybe every 12 or 16 weeks with EYLEA high dose and Vabysmo. So how do you view DURAVYU as fitting into the evolving landscape in wet AMD?
Yeah, that's a good question, and it comes up often. And I'll come back to what I talked to earlier is, we are not another anti-VEGF, right? So what DURAVYU brings to this patient population is another mechanism of action. We've shown in animal studies that we had neural protection, and we're seeing, I'll say, hints of that in the DAVIO 2 data. If you look at the subgroup analysis, where our, the unsupplemented eyes, the DURAVYU eyes actually did better than EYLEA through six months. And so while what the current market tells us is there's still a meaningful need for duration, you know, all of that aside. So, you know, we learned at ASRS that, you know, Vabysmo's had an amazing year.
It's a billion-dollar drug, and there was a presentation by RCA, the Retina Consultants of America, that basically showed that Vabysmo extended duration by eight days, and it's a billion-dollar drug. So there remains a huge opportunity just on duration alone. And again, as what we've really been positioning DURAVYU for is it's a maintenance therapy, and, you know, we are going to work with, not instead of-
... these biologics.
So what kind of patients do you see as being early adopters of DURAVYU, and how do you think that demographic might change when you're thinking about the eventual potential addressable market?
Yeah, so you know, we're spending. Well, we have a pre-commercial team spending a lot of time on that now, and I think if you poll a range of KOLs, you're going to get a range of answers-
... depending on their practice, and I think certainly, there's probably going to be an immediate push for those high-need patients to give them something else. But, you know, what we suspect will happen in a majority of cases is, you know, these doctors are very familiar with the treat and extend protocol, where, you know, you'll have a patient, they're maintained, you're going to put in DURAVYU, you bring them back in a month, and then you'll learn that treatment process, and so we expect a mix of all of that-
As you know, we hopefully, as we get a label, you know, that shows for both previously treated and naive.
Great. We recently got the first approval of the first at-home OCT device. How do you foresee at-home OCT playing a role in the rollout of DURAVYU and long-acting inserts?
Yeah, so we're actually very excited about home OCT. I think if you talk to these physician practices in general, most of... You know, there are very few retinal specialists in the United States, and a lot of them are injecting 70, 80, 90 times a day, and they're really excited about the prospect of DURAVYU because they have a visit burden. You know, And you have the GA drugs now, where you're having these patients come in, and so if we can repeat the DAVIO 2 data, where we can take two-thirds of patients and put them on an extended regimen, home OCT plays beautifully in that because they can monitor them remotely, and if they see signs from home OCT, bring them in, and it's going to meaningfully reduce the visit burden going on in the office.
So we see it as certainly a net positive for us.
Great. And so let's hit on nonproliferative diabetic retinopathy just briefly. I know not a huge area of focus at the time being, but if you could just kind of speak to the read-through that you see from the data that you had earlier this year in NPDR and, you know, kind of tying that back to the wet AMD data that you've already generated.
Sure. So I think first and foremost, you know, the DAVIO 2 wet AMD data stands on its own. It's been looked at by, you know, everyone, and it's just remarkable data. NPDR is a very different disease. It's early-stage diabetic eye disease. I think you've now seen two TKI programs studying that with sort of similar outcomes, and it's very clear to us it's disease specific, and while we did miss a primary endpoint, which was reducing improving, we did show an impact in progression of disease, along with again small n, but we did show a reduction in progression to DME. It's a very complicated, you know, it's a very interesting indication. I think you know there's two, both EYLEA and Lucentis are approved, and NPDR are not used.
It's a patient population that really doesn't go to the doctor, and so what we liked about the opportunity initially was, you know, the ability to do a six-month therapy. But I think what we've learned is there's a lot more complication, at least in the early stage of diabetic eye disease, where the TKIs may not play, even though we did see a biological effect, and we certainly continued our safety profile.
Okay. And then so in light of that data, kind of walk us through the trial design for DURAVYU in diabetic macular edema?
... different diabetic driven disease, and help us set expectations for those data in one Q.
Yeah, so we're very cautious to not set expectations. But I think what's interesting about DME, it's more like wet AMD than NPDR in the sense that it's an exudative disease, and we saw in DAVIO2 that our program had, you know, really great impact on that. And so the VERONA trial, which is the DME trial, was started this January, and remember, that trial was designed before we had the DAVIO2 data. So I think, you know, we're, you know, there's a lot of learnings from DAVIO2 that, you know, retrospectively we could have applied, but at the end of the day, we're...
The study design is really to get experience in the DME population, and so we're doing two doses of DURAVYU, 1.3, 2.7, so actually similar dosing to what we're doing in the wet AMD phase III s, and then aflibercept. So everyone gets a single dose of aflibercept. The treatment arms get the 1.3 or the 2.7 mg dose and then just the single treatment in the control arm, and then we're watching them for six months for supplemental therapy and BCVA.
Okay, and how should we think about one loading dose versus I think the EYLEA label includes multiple loading doses in a disease like DME?
Yeah, so I think we'll see, right? So I think the concept of that initial trial design was really to get experience and see how the drug did. I think there's certainly an argument out there, and it's come up by a number of investors to consider, you know, doing, expanding it and adding a cohort with three loading doses. But, again, I think we're... remember, we're a zero-order delivery kinetics, and we know we deliver drug, at least in animals, for about nine months. So we should get a snapshot in Q1 next year on what we're gonna see in DME patients.
Okay. And then, so let's touch on the pipeline as well. So EYP-2301, your erodible Durasert Tie-2 agonist. So, talk to us about the next steps for that program.
Yeah, so EYP-2301 is a pretty novel molecule. It's razuprotafib. It was previously known as AKB-9778, and it was deliver- it was delivered subcutaneously. And it actually had very good anatomical effect in wet AMD, but it didn't have the appropriate BCVA impact. So we actually acquired that asset a number of years ago. We've reformulated it into Durasert E as a six-month treatment. And so we are-- the concept there is to pot- to potentially use it in conjunction with an anti-VEGF. We haven't really worked through that study design, but there's potential for superiority, and if it works, you know, it's another multi-billion dollar product opportunity. So we have spent a lot of time this year on that program.
We're expecting preclinical talks and PK later this year, and we'll make our decisions sometime next year on moving that program forward.
Okay, so should we think about that as a combination partner with an anti-VEGF?
I think if you look at the data that's out there, you know, this, it's a... these Tie-2 agonists, I mean, so if you're familiar with Vabysmo, Vabysmo works on the Ang-2. We're working on, Tie-2 agonist-
which we think is the better pathway for vascular stability. And I think if you look at the data to date, you need that VEGF suppression-
along with that program.
Understood. And then, so you're also exploring the use of your technology in dry AMD or GA. You have a collaboration with Rallybio. Any kind of update on that program?
Yeah, so we continue to evaluate a number of molecules in GA, including the C5 program with Rally. You know, it's. We're watching the GA market evolve. You've got two approved drugs, and the clinical regulatory pathway continues to evolve. I think that remains an area of interest for us, and that's sort of, I would say, second to what we expect to do with EYP-2301.
Okay, understood. And then, I've gotten a couple inbounds in the last couple of weeks. There was a warning letter that you received from the FDA. Can you kind of just talk about the scope of that warning letter?
Yeah, so the warning letter, and we actually disclosed this in our second quarter 10-Q, so it's not new news, although the warning letter was recently published by FDA, and there's a little bit of context missing, including a number of our responses that were not included in the letter. But that said, we are focused on quality as an organization, and we expect to resolve the warning letter, you know, in the coming months. I think importantly, it was specific to YUTIQ. YUTIQ is a commercial product that we developed. We sold that to Alimera about 18 months ago, and we continue, for now, to be the contract manufacturer for them. And so this was the result of an FDA inspection for that commercial process, and the team is working diligently to resolve that.
In fact, at the you know, we've resolved, you know, the vast majority of those observations.
Okay.
And-
Does that have any read-through to the DURAVYU manufacturing?
It does not, and we talked about that in Q2. It was specific to YUTIQ manufacturing, which is commercial. DURAVYU continues to be produced under, you know, the clinical supply. And I'll remind you that, you know, for DURAVYU, and they're very different processes. YUTIQ is a very manual process. It's a, got a polyimide coating, it's capped at the end, and, you know, it's a very manual process. DURAVYU is non-coated, it's semi-automated, and we are scaling up our Northbridge, Massachusetts facility, which, we've recently occupied, and that's gonna be our commercial site. It's state-of-the-art facility. We've had FDA involvement from the beginning, and that's where, ultimately we'll make, registration batches and commercial product, for DURAVYU.
Fantastic. So now we don't have too much time left, but let's just touch on current cash, and what your cash runway is.
Yeah, so we ended Q2 with about $280 million of cash, and our cash guidance has been unchanged, which is through top-line data for phase III wet AMD in 2026. We did, in our second quarter Q, announce that we raised about $12 million off our ATM, and that was on a reverse inquiry on the heels of our R&D day. And so, you know, we are comfortable with our cash. I think you've known us long enough. We're good at execution. We're very good at marshaling and shepherding our cash, and look forward to updating you on the trials as we go forward.
Fantastic. And so just in the last minute here, I'll just turn it back to you, George, to kind of wrap up on kind of why investors should be paying attention to EyePoint over the next six to 12 months.
Yeah, so I, you know, I think it's important to, you know, look back at where EyePoint's been the last three years. We've been a story in execution. You know, we, it was not that long ago we were in phase I , and now we're about to start, you know, phase III trials in wet AMD. It's a huge market opportunity. We're going into the phase III trials with a robust phase II data set. We have met with FDA several times, including an end-of-phase II meeting. We have alignment with them on our study design, on our non-inferiority margin, on our use of sham, and while the, there seems to be swirling conversations out there, we are in motion and ready to go. We've got, you know, to your earlier question, we've got amazing investigator excitement in the trial.
We have over 130 sites signed up, and we expect to hit the ground running in a meaningful way, so stay tuned, because, you know, we're excited to get it going.
Fantastic. Awesome. Well, thank you so much, George, for being with us.
Thank you. Thanks, Colleen .