EyePoint, Inc. (EYPT) Earnings Call Transcript & Summary

Welcome to the UBS Virtual event. I would now like to pass the call over to Eliana Merle.

Hey, guys, thanks so much for joining us. Happy to have EyePoint here with us here for a fireside chat. Joining us from EyePoint is Jay Duker, President and Chief Executive Officer; as well as George Elston, Chief Financial Officer. Thank you guys for making the time. Maybe just to kick it off, can you tell us a bit about EyePoint's platform and your technology that differentiates your approach?

Sure, and thanks for having us, Ellie. So EyePoint, what we really do at our heart is drug delivery to the back of the eye. And our platform to do that is called Durasert. Durasert has been in 4 FDA group products and a nonerodable form. Our lead product, which was formerly known as EYP-1901 is now being called DURAVYU. That also is in Durasert, but it's in Durasert E for erodible. The previous iterations of the product had a nonerodible polyamide shell. That was not necessary for our DURAVYU.So we've removed the shell making the entire insert bioerodible. So the nice part about what we're doing is that we have 4 FDA approved products with essentially the same platform. The matrix that we use to hold the ends and the drug together in the insert has been used in tens of thousands of patients. So there's a long safety history that's quite positive for this technology. The technology is shifting stored at room temperature and comes in prepackaged, well-tested injector system that's sterile. So there's no mixing that the physicians need to do.

Makes sense. Can you elaborate a little bit on how the Durasert technology works and why sustained delivery is so important in the context of wet AMD?

Sure. So first of all, what we're using in Durasert is vorolanib, which is a small molecule tyrosine kinase inhibitor. And if one were to inject a small molecule into the eye intravitreally like for how we treat wet AMD, without a delivery system, it would be gone in days. So in order to make a small molecule last longer, you need a delivery system. And the second part of the equation is that what's lacking right now in wet AMD care's durability. We have plenty of good options that are short-acting options that are safe and effective, but none of them really last very long. So by using a combination of a small molecule TKI vorolanib, with our Durasert E technology, we're able to deliver therapeutic levels of drug for at least 6 months and perhaps up to 9 months in humans with a single injection. And that's really our advantage. The big advantage of DURAVYU over other approaches is longevity.

Makes sense. And yes, I guess, starting with wet AMD and your Phase II results. Can you walk us through the design of the Phase II DAVIO 2 trial? And what your considerations were for making the design choices that you did?

Sure. So that's really an easy answer because I'll just go back historically. Very early on in the development of EYP-1901, we recognize that our advantage was longevity. In that, we decided that we were going to go for a label of maintenance therapy in wet AMD for either previously treated or naive patients after a load with anti-VEGF. So that was the part of the TPP that we had decided on long ago. After we got positive Phase I data, internally, there was a discussion about whether to take this program directly to Phase III. And so we went to the FDA in 2022 with a Type C meeting, laid out a Phase III program. They commented, we made some changes. And at the end, they had given it its blessing. So we had a Phase III design in 2022. Internally, we then decided it made more sense to do more of a traditional drug development approach into a Phase II trial. But we designed the Phase II trial, DAVIO 2 trial around what the FDA had told us. Now there were a few changes, for example, the Phase II trial did not involve reinjection of our drug. The Phase IIIs will. The Phase II trial had a primary endpoint of combined 28 and 32 weeks around 8 months. The Phase III trials, the FDA had discussed with us and we agreed would have a 1-year endpoint, combined 52, 56 weeks. But overall, other than that, the Phase II design was very similar to what the FDA had agreed upon. So we executed that trial. And as I think you know and we've reported back in December, very good top line results. We hit the primary end point of noninferiority change in visual acuity against an Eylea on-label control with a change in difference in letters at the end of 8 months of less than half a letter. And more recently, we reported 12-month data, which even without a reinjection of our drug, continue to show excellent visual stability in the DURAVYU-treated eyes. Safety has not been a concern in any of the trials. In DAVIO 2, we had no ocular or systemic SAEs attributable to our drug or to the insert. And that's been true across all the trials that we've done. We've now treated about 191 patients with DURAVYU, and we've had no ocular or systemic SAEs. And so safety is really important in the retina space, as I'm sure you and others who follow it know. And so while that's not the primary endpoint, you can call it primary endpoint 1.1, you have to have safety, and we've really shown that. And I want to add, one of the other interesting things about vorolanib is it was studied as an oral agent in wet AMD several years ago. And that we have a database of about 150 patients who took it orally with no ocular SAEs related to vorolanib. So we have a very large safety pace right now of patients treated with vorolanib. We also -- the secondary endpoints, we hit them all. We reduced the treatment burden by about 80%, whether you look at it prospectively against the Eylea control or you look at it retrospectively against history. We had 2/3 of the patients able to go up to 6 months after DURAVYU went in without a supplement. In the anatomic data, that's the measurement of the retinal thickness that we do on optical coherence tomography or OCT. That looked really good, too. There was no significant difference between the Eylea arm in either of the DURAVYU arms. So overall, the Phase II really hit the top line and the secondary endpoints really [indiscernible].

Makes sense. It's exciting data. And in terms of your Phase III design and your registrational strategy. I guess you have 2 pivotal trials about to start in wet AMD. Can you give us an overview of these trial designs and your rationale?

Sure. So first, the rationale between noninferiority trial designs is well established with the FDA. The last 5 approvals for wet AMD drugs have been noninferiority. And in order to do a noninferiority trial, you need a noninferiority margin, and that margin has been designated as 4.5 letters. So that the lower limit of the confidence interval when you do the statistics at the end of the trial can't cross minus 4.5 letters. I want to go back to our results in DAVIO 2 just for a moment because the noninferiority confidence interval didn't cross 2.6 letters in DAVIO 2. So that we were, from a visual acuity perspective, miles away from the non-inferiority margin in DAVIO 2, which gives us great confidence for the pivotals. So that's the overall design, noninferiority against a standard Eylea control. We're going to use 1 dose of our drug that doses 2.7 milligrams. That dose is achieved by injecting 2 inserts simultaneously in our injection system. We can actually inject up to 3 inserts with a single injection with our injection system. So that 2.7 mimics of about the 3-milligram high dose that we used in Phase II. All of the patients in the trial will get loaded with Eylea. What that means is day 1, everyone gets an Eylea, they get randomized at day 1. Week 4, everyone gets Eylea. Week 8, everyone gets Eylea and then 30 minutes later, they either get their first dose of DURAVYU or if they're randomized to the Eylea arm, they get a sham. They then come in monthly. Every other month, the Eylea arm gets another Eylea. In the DURAVYU arm, every other month will get a sham, except at month 8, they'll get another DURAVYU. So there's no early rescue with DURAVYU. It's every 6-month drug. And that will continue. The primary endpoint for efficacy is a combined visual acuity 52, 56 weeks combined, but the study will go on for 2 years for safety. And that's important because the FDA made it clear, and you can see with other programs as well, to get a label for continued reinjection, you have to show safety over that 2 years. And so we're excited to be perhaps the only program that's got 2 pivotal trials in sustained release with reinjection. And again, from a perspective of what the patients want and what the physicians want, reinjection is important because it gives the physicians more control over the long-term treatment of their patients. Other highlights of the trial, just like in DAVIO 2. In the pivotal trials, there will be a masked physician who determines if a rescue criteria is met. And therefore, theoretically and frankly, practically, the Eylea arm can also receive a rescue. And that actually happened in DAVIO 2. By month 8, 6% of the Eylea arm had gotten a rescue treatment despite the fact that they had gotten every other month Eylea. What that tells you is that we enrolled a very tough-to-treat population because even every other month, Eylea didn't keep them under control. And I think that number by month 12 expanded to 13% had been rescued. So when we look at the pivotal trial, there'll be rescues in the pivotal II. We hope and expect the numbers to be less in the DURAVYU arms for several reasons. But we're also going to be compared to the rescue number in the Eylea arm, not just in the DURAVYU arm, which from a statistical perspective, we believe, will be helpful. So the rescue criteria or supplement criteria, the major one that we're using is the same major one we used in Phase II, no different 5-letter loss from best on-study with 75 microns of new fluid due to wet AMD. There will also be a mandated rescue for hemorrhage if it's confirmed by an independent retina specialist. And that's really the extent of the supplement criteria that we'll use in the Phase III. One of the other things to note is in the Phase II, 20% of the supplements given in the DURAVYU arms did not meet criteria. We gave the Phase II investigators leeway to rescue if they thought it was in the patient's best interest. And we're really going to ask them to stick to the protocol for the Phase III because we'd like to see fewer rescues. So on to another change is we're enrolling both previously treated and naive patients into the pivotal trials, where we had only enrolled previously treated before. There are several reasons why we're doing that. The first reason is that when we evaluated the patients who did best in DAVIO 2, the patients who didn't need many rescues, it appeared that the eyes that had been recently diagnosed actually did better than the group as a whole, with 80% of them making it through 8 months without a supplement. The second reason is we enrolled a really tough-to-treat population in DAVIO 2. How do we know that? Well, first of all, historically. Historically, the population we enrolled had an average of 10 injections leading into the year, leading into the trial. That's a lot because in the real world, it's about 6 injections or less. The second way we know it is we had rescues in the Eylea arm, which I mentioned. The third way you can tell is if you look at our data from the Phase II and you look at the OCT data from the Eylea arm, what you'll notice is every 2 months, the OCTs got wetter in the Eylea arm. That tells you that every other month Eylea was not controlling all those patients, and they were tough to treat. So let's go back to why naive patients. Well, naive patients, depends who you ask, but anywhere from 20%, 25%, maybe up to 30% of the naive population probably can get by with less than every other month Eylea. Well, that, I think where our drug should do very well with those patients. The ones who are not really dependent that much on anti-VEGF frequently. In which case, we think that our results in that full population should be even better than what we saw in DAVIO 2. So we are enrolling naive and previously treated. I think that also gives us an enrollment advantage because most of the wet AMD trials just enroll naive patients. So overall, those are the major changes from DAVIO 2. And again, the changes are things that we knew about ahead of time because we had discussed with the FDA and aligned with what they were, for example, the reinjection is okay with them in the 1-year endpoint, but also using naive, I think that that's actually going to help us.

Great. It's a very helpful overview. And just in terms of like the status of initiating these trials and given the many trials ongoing in this space, what are your perspective on how long it will take to enroll the Phase III program?

So let me start off first by saying that there's a lot of reasons. I'm glad we ran a Phase II and didn't go right to pivotal. But one of them is we learned a lot about how to recruit these trials. In our Phase II trial, we enrolled 160 patients in about 8 months using 70 centers. Most of those patients were enrolled in the last 3 months of the trial because there were lessons that we learned in the first few months that we're going to be able to apply to the pivotal trials. And we already are. We have right now over 140 sites that have agreed and we want them to be in the trial. We started activating those sites. And what we expect is when we get the first patient randomized dose that's same day, obviously, is we're not just going to have 1 or 2 centers up and running. We hope to have a dozen centers up and running with another 50 or 60 coming online in the next few weeks. So we're really going to do a very quick ramp-up of the sites. There's always really been competition for AMD trials when you go back. There are a few that are open, some of which we're not directly competing with because the inclusion criteria is a little bit different. And others that companies reported that they'll be starting up in the Q1 or Q2 of next year, where we hope to have a really good number of patients already in our trial or trials, I should say, since the second trial is expected to start within the first few months of the first. So we are doing a lot of things to ensure that our trials are on the top of investigators' minds. But I think equally importantly, our trial is very easy for investigators to understand because they run noninferiority trials before. We have a fixed interval for both dugs and everybody is getting treated. And there is the opportunity to rescue if anyone's getting undertreated. I think it's a very easy trial for patients to understand, and that makes it recruiting easier as well. So there's a lot of things that we're doing. Sometimes they're just basic blocking and tackling things that make it easier for the sites to bring patients in. But having a lot of sites and having great communication and listening to the sites about what they want and how to make it easier for them to enroll. Those are many of the lessons that we learned in DAVIO 2. So on to the timing, I think you can look at other wet AMD trials and see how long they take to enroll. Generally, they're a year or less, and we are quite optimistic we can meet or beat that. What I can say, and this is certainly not guidance, and it's low probability. But if we enroll the Phase IIIs at the same pace that we enrolled at the end of DAVIO 2, we could enroll this trial much faster. So that's what we're going for. I can't say we're going to be there, but we're optimistic that we can enroll both trials in less than a year.