Good morning, everyone. Yatin Suneja from Guggenheim. Our next presenting company is EyePoint. From the company, we have Chief Financial Officer George Elston. George, why don't you give maybe two minutes overview, what you guys are doing, where you are, what are the next milestone? And then after that, I want to address three things. Number one would be, you know, what you need to sort of get an alignment on with the FDA with regards to the study design and the endpoints. Two, the expectations around PAVIA study. And three, how are you thinking about commercialization?
Great. Thanks, and thanks, Yatin, and thanks to Guggenheim for having us here in this great venue, and thanks to all of you for being up early. I think a lot of us are East Coasters. So, EyePoint, we're really a transformed story. The company's been around a long time, but we've really done a heavy pivot into biotech and a biotech pipeline over the last few years. We have a platform technology called Durasert. It's been in four FDA-approved products in the eye. All of those have now been licensed out, and, you know, until a year ago May, we were a commercial company.
We have a very exciting molecule called vorolanib, which we'll get into, for wet AMD, diabetic retinopathy, and other indications, which just had really fantastic Phase II data in December. Our pivot was to move away from being a commercial company. We sold the YUTIQ franchise to Alimera last year. We paid off our debt. We raised meaningful equity in a follow-on last year, ending 2023 with $331 million.
We're fully funded through our phase IIIs in wet AMD, which is sometime in 2026, and look to build our pipeline behind Durasert. Quickly on Durasert, there's a little bit of confusion in this space because the technology has been there for some time, and a lot of people are familiar with products like YUTIQ and ILUVIEN in the eye. Those are non-erodible formulations. While it has essentially the same core matrix as EYP-1901, which is our lead program with vorolanib, a TKI, t hose molecules or those drugs delivered a steroid, and they delivered over three years, and so a polyamide shell was used to control that release.
For EYP-1901 and our pipeline forward, we have essentially removed that polyamide shell because we know we're gonna be redosing every six months. It's fully bio-erodible. Each insert is 90+% drug, and that drug is gone in nine months. And, and we're moving forward into phase III later this year, which will include, and we'll get to that in your questions, with redosing.
So you're expected to meet with the FDA, I think, in the next few weeks or so. Could you just talk about the element where you need an alignment on with the FDA? And if you can also highlight some key differences between DAVIO2 and the pivotal program that you will be running in wet AMD.
Sure. And maybe if I can just recap DAVIO2 quickly. So, DAVIO2 was our wet AMD trial. It was a 260-patient trial. We showed in a non-inferiority trial against the aflibercept, which is Eylea on label. And what we demonstrated in that trial was statistical non-inferiority with a fairly small N. We had a meaningful 80%+ reduction in treatment burden, and we were able to take two-thirds of patients out six months without needing any other drug. And in fact, when we looked at a subset analysis of those patients that required no rescue, the 1901 arms did better.
And so we're very encouraged by that data, and now we're looking forward to our end-of-Phase II meeting with FDA. I'll remind everyone that we had a Type C meeting with FDA back in 2022, and that was on the heels of the DAVIO Phase I data. The purpose of that Type C was we were originally thinking about going straight to pivotal, and so the FDA has already seen our protocol, our stats plan for that program, and they blessed it back at that time. There's a lot of discussion about the draft guidelines for wet AMD trials.
Our Type C minutes and the draft guidelines for non-inferiority are exactly the same, and so we feel very confident going into this end-of-Phase II meeting with FDA. We've got our minutes in hand. We've got really robust phase II data, and just as a reminder, every drug in wet AMD that has been approved since Lucentis has been approved on a non-inferiority trial. So, we're feeling very good about it. We're gonna talk about the N. I think the good news, and we changed our messaging really at J.P. Morgan conference this year.
When we were out meeting with investors last year, you know, we didn't know the stats. We didn't know how well 1901 would do in the phase II trial. And so at the time, we were thinking we were looking at 900+ patient trials for Phase IIIs. The good news from DAVIO2 is our, our N size for the trials is more like 300-400 because we need sizing for safety, not necessarily sizing for statistics. And so the difference is, you know, to your next point, the differences between DAVIO2 and the Phase IIIs, the first, obviously, is it's a 12-month endpoint, and that's based upon FDA requirements.
We're going to be redosing 1901 in the phase III trial every six months. I think it's important to note, we're the only sustained delivery program in development that's redosing the drug on a regular basis. So we'll we would like to have that label on the end of that trial. We're actually going into that trial with one and two inserts as the high and low dose versus the two and three, because there was really no dosing change. We didn't see any change between the two doses, and that's largely because of zero-order kinetic delivery.
In terms of actually on your previous point where you make, or you change the message at J.P. Morgan, you should do it only at Guggenheim and conferences.
Well, if you were in January, we certainly would have done that. But remember, we raised money in December, and I think that message was very important because we were actively looking for a partner for phase three, because it was a daunting cost.
Yeah.
Now we're looking at smaller trials. We raised adequate funding. We're going to keep that value, and, you know, potentially we'll bring in maybe a commercial partner ex-U.S. when that time comes. But where we sit today, we're very comfortable about our ability to execute. I think we've got a great track record of that, and, we're marching ahead very, rapidly to Phase III this year.
A few more questions on the FDA interaction. So you have to negotiate the N, the number of patients. I think you're re-dosing it, so that's, that's a subtle difference between Phase II and Phase III. What about the type of patient would you be required to enroll, let's say, more severe or less severe patients? Just curious on the spectrum of disease, how you're thinking about the patient enrollment in the study.
Yeah, so that's where we're spending a lot of our time right now. I think w e don't expect too much of a change in the patient population between DAVIO2 and the Phase III trials, which are named LUGANO and LUCIA. You know, there is, I think, you know, one thing we've talked about publicly is the FDA is probably not going to let us enroll 20/20 patients. We did have some of that, but that's okay because everyone gets a loading dose, and I think everyone's going to start as dry as they can be as they go into this trial. You know, we hope to repeat the same data that we saw in DAVIO2.
You know, on the sizing, you know, the FDA has said publicly, you need about 400 patients for safety in your go-to-market dose. So that's really what's driving the N of our trials. You know, further discussion, it may be somewhere between 300 and 400, but we're going to size, so we don't miss it due to dropouts.
So you meet with the FDA, let's say in the next few weeks, when would you be able to start, how quickly you might be able to enroll, and when should we at least expect data for the first study?
Yeah. So, we're continuing to move forward very aggressively. I think the good news for us is we make EYP-1901 in our Watertown facility. We've got a very amazing team there that is essentially working around the clock to be prepared for the clinical trials. We're also building a commercial manufacturing facility in central Massachusetts to support commercial manufacturing. So the team is well underway to prepare for this. I think as you think about the clinical trial enrollment, the good news for us is we just completed. DAVIO2 is actually still ongoing. It's a 12-month trial.
There are about 70 sites in DAVIO2 here in the U.S. We anticipate using most of them in the phase, in the Phase IIIs. And so we think we can move very quickly to that.
I think once we get alignment with FDA, we'll update the street once we receive those minutes, and, we'll be moving ahead. We've guided to the initiation of the Phase III trial first, second half of this year, and then the second phase III to start several months later. You know, enrollment, we're hoping to do better than, you know, I think typical enrollment for a phase wet AMD phase III is about a year. We're hoping to do better than that because we've got a number of sites up and running, and the second trial will be OUS and US, and so, you know, we've got that in motion as well.
Okay, then moving on to other indications. Could you talk about the PAVIA study? What are the expectation? Maybe just orient our investors also, the endpoint and what exactly you want to see, because, you know, the wet AMD don't really get used in, in that indication.
Yeah, so the PAVIA trial is our clinical trial in non-proliferative diabetic retinopathy, 77-patient trial. We completed enrollment in that trial last May. It's a nine-month endpoint, so we're coming up on that timeline. We've guided, you know, Q2 for that. It's the endpoint is a two-step reduction in the DRSS score, which stands for Diabetic Retinopathy Severity Scale. You know, what's unique about NPDR patients is they're working age, they typically don't feel their disease, and as a result, they don't go to their doctor or they don't take treatment. Both Eylea and Lucentis are approved for that indication, but they're largely not used due to the frequency of injection.
What we like about 1901 here is if we can show a meaningful reduction in this DRSS score, we could have a product that's going to match the annual cadence of the patient visiting their doctor. They're in the chair, and the doctor can, you know, simply say, "Listen, you're here. I can protect you for the next 9-12 months." So that's our concept for 1901 PAVIA. As we think about, you know, what would be the floor, we're not guiding, but what would be the floor to move forward? In talking with KOLs, they say if you can get one out of three, that's a product that they would use.
If you look historically with the any drug in these VEGF pathways, if they worked in one indication, they've worked in all. So we do go in with a little bit of confidence, but you just don't know. Both Eylea and Lucentis were in that 50%-60% reduction range, and so, you know, we're bullish about it, but you know, we'll know in a few months.
Very good. So the threshold to move forward is about 35%?
About a third, yeah.
About a third. Okay, very good. How big is that market?
So NPDR is a huge market. And if you take the continuum of the diabetic population, you know, every You know, DME is the big indication because it's so sight threatening. But every DME patient has NPDR. That's where it starts. And, you know, as we think about the continuum for this disease, we also have a DME trial in motion, which is the VERONA trial.
We expect that to conclude recruitment mid-year and read out early next year. It's, you know, it's a very meaningful, you know, almost 10 million patients in the U.S., about three of them, three million patients, have NPDR. And so you can, you know, this has potential to be a another multibillion-dollar opportunity, if we get the outcome we expect.
The development or the regulatory path here is a little bit less, I would say, stringent, in the sense that you could do a placebo-controlled study or a sham control study?
Yeah. And, you know, unlike the noise around wet AMD, and you cannot do a sham control trial in wet AMD, which we're not doing, we're doing it in an aflibercept control trial. The, because the standard of care in NPDR is observation, the FDA has, you know, advised, and it's. We expect it still to be true, that you can do a sham control, and that's what we're doing in the phase II trial. So the Phase III should be very quick to accelerate and move forward.
Okay, final question on the DME side. Obviously, that study most likely gonna read next year. Is there any particular dosing work that you are doing in that study? And the reason I ask is because in the Phase III wet AMD study, you're going with the 1, 1-ish milligram dose. We haven't really seen a lot of data on the 1mg , so I am curious to understand if there is more work that you might be doing in DME study before that we should be able to see.
Yeah. So just to come back to Durasert. So the beauty of the Durasert technology is it's sustained release zero-order kinetics, which means it's giving constant dosing 24/7. And in what we've seen in our trials, in both in animals and now in humans, is we get a little bit of burst off the surface of the insert, and then you're getting sustained release for about nine months. And that's really the beauty of this technology.
We think once that constant pressure on that VEGF receptor is really an important part of this MOA for this program. So in the DAVIO trial, which was the Phase I, we actually tested two different doses. We tested, and think about it as each insert, they're all consistent. So we had a 440 microgram dose, we had a 1 mg dose, a 2 mg dose, and a 3 mg dose, and it was really one, two, or three inserts. And they, if you go back and look at the DAVIO 2 trial, there was really no dose response, which to us is not a surprise, because we're even at the 2 mg dose, we were orders of magnitude above IC50s.
With the 1 mg dose, we're also orders of magnitude. And so one thing we want to explore in the phase III is to see if we can actually, you know, using a single insert and two insert dose, to have, maybe have an effect with a single insert. And so we do have some flexibility on that payload.
The VERONA trial in DME is actually a higher payload insert. It's about 1.3mg per insert, and it's, you know, same size, same manufacturing process, we're just able to put more drug in. And as we move forward, for end of phase II meeting, as we start to get a little more experience in this DME population, you know, we haven't finalized the payload, for phase III, but it's certainly gonna be at least 1 mg per insert. So we, you know, we know 2 mg worked in DAVIO2. We wanna make sure we bracket around that.
All right. Very good, thank you so much, George.
Appreciate it. Thank you.