Ladies and gentlemen, thank you for standing by. Welcome to the EyePoint Pharmaceuticals Virtual Key Opinion Leader event. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to EyePoint Pharmaceuticals' President and Chief Executive Officer, Dr. Jay Duker. Please go ahead.
Thank you. Good morning to everyone, and thank you so much for joining EyePoint Pharmaceuticals Virtual KOL event. I am Jay Duker, President and CEO of EyePoint Pharmaceuticals. Before we begin with our program, I want to remind you that various remarks we will make today constitute forward-looking statements. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, financial projections, and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements. Please refer to our most recent annual report on Form 10-K, which is on file with the SEC, and other filings that we may make with the SEC in the future.
With me today are two prominent retina specialists and clinical researchers, David Lally, MD, who practices in New England, and David Boyer, MD, who practices in Los Angeles. Welcome to both of you, and special thanks to Dr. Boyer, who got up very early this morning to join us. Both of these KOLs have a lot in common, aside from their first names. They are some of the two superb retina specialists in the U.S. They trained at some of the best institutions in the world. Both are excellent clinical researchers, prominent KOLs, and well-respected for their insight and honesty. Again, welcome to both of you, Davids. Here is our agenda for the morning's program, and let me start with our company overview. First of all, at its heart, EyePoint is a drug delivery company to the back of the eye.
Our pipeline represents a potential multibillion-dollar opportunity, and it features our bio-erodible Durasert E™ intravitreal technology for drug delivery. Our main candidate in that pipeline is EYP-1901. That's a small molecule tyrosine kinase inhibitor called vorolanib in Durasert E™ bioerodible technology. And we're going to spend essentially most or all of today's discussion talking about its use in wet age-related macular degeneration. As you may be aware, we also have a phase II non-proliferative diabetic retinopathy study that should read out in Q2 of 2024, and we expect to initiate a phase II trial in diabetic macular edema in Q1 2024. We recently announced a new addition to our pipeline, EYP-2301. This is a small molecule razuprotafib, which is a patened Tie-2 agonist for serious retinal diseases, and this is also in our Durasert E™ technology.
Durasert is a proven safe intravitreal technology for drug delivery. There are four FDA-approved products that feature Durasert, and we estimate that over 80,000 patients worldwide have received one with a very, very clean safety record. The company features a strong balance sheet. As of September 30, we had $136 million in cash and investments, with a cash runway into 2025. So I'm sure you're aware, but I do want to reiterate that while we have some excellent treatments for wet age-related macular degeneration, there exists a significant need for more durable therapies. Retina specialists themselves estimate that there is chronic undertreatment of wet AMD patients due to patient noncompliance and scheduling limitations in our offices.
Most of us do what we call a treat-and-extend protocol, and even though this minimizes visits, it still puts a significant burden on physicians and patients to keep up with the schedule. Even a small delay in care or missed visits can result in visual loss, and we learned that during COVID. There's a paper that suggests that missing even one visit in these wet AMD or DME diseases can result in visual loss. Since we have an aging population, we're going to see significantly more patients with VEGF-mediated diseases filling up our offices even more. EYP-1901, again, we are studying it as a potential sustained delivery at six-month intervals for wet age-related macular degeneration. On this slide, you can see a picture of one of our inserts.
They are small cylinders that are injected into the eye in the office. They're heavier than water. They sink to the bottom of the vitreous cavity, and we can inject multiple inserts with a single injection. Again, they feature vorolanib, which has a potential new mechanism of action in the treatment of wet AMD. One of the features of all of the Durasert inserts that's really unique, and we think is a difference maker, is what's called zero-order kinetics. After an initial burst of drug, the vorolanib release levels get steady after a few weeks and remain steady for up to nine months at therapeutic levels. This gives us the opportunity to do what's been called microdosing, which means relatively small doses of the medication can be very effective at blocking the receptors in the long term.
Using EYP-1901, we see immediate bioavailability as well in vivo in animals, and sustained release in animals for up to nine months. We've shown positive safety and efficacy data from a phase I trial in wet AMD, and again, our phase II trial in wet AMD, the DAVIO 2 trial, we expect to have top-line results in under four weeks. One other thing that we'd like to note, and we think is also a difference maker, is EYP-1901, of course, comes preloaded in syringes, and it can be stored at ambient temperature. Vorolanib does bring the potential of a new mechanism of action to the treatment of VEGF-mediated diseases. It acts at the receptor level, and as such, blocks all the VEGF receptors, including the blockage of all isoforms of VEGF.
We also block PDGF, which theoretically should result in reduced fibrosis, and in the long term, the development of fibrosis can be something that is associated with chronic visual loss in wet AMD. So the DAVIO phase I clinical trial in wet AMD was a typical dose escalation trial for safety. This slide summarizes the trial. It was multicenter. We went through four different dosing levels, and we enrolled a population of previously treated wet AMD patients who were pretty heavily pretreated. 8.6 mean injections for the group for the year preceding enrollment. On average, in the United States, doctors deliver anti-VEGF for wet AMD about every seven to eight weeks, meaning on average, patients get about six injections a year. So this is a pretty heavily pretreated group.
We didn't have any preconceived idea of how our drug might work with fluid or without, so we enrolled patients both with and without active fluid, and they had to have a minimum of 3 anti-VEGF injections in the previous six months. So all of these patients were not treatment naive. Everybody got one injection of an anti-VEGF followed by EYP-1901 a week later, and of course, the primary endpoints in the phase I trial are safety, but we also looked at indicators of efficacy. This slide shows you the top-line results from the phase I trial. Again, as a reminder, no drug-related ocular SAEs, no drug-related systemic SAEs, and the majority of ocular AEs were mild and expected with an intravitreal administration.
From the efficacy and durability side, at six months, the patients who received EYP-1901 lost, on average, -2.5 letters. There was a 75% reduction in treatment burden, and over 1/2 the eyes were supplement-free up to six months. The OCTs were rock stable. We also went on to do a DAVIO subgroup analysis, which included nine of the 17 patients from the phase I who entered the study dry. These were what Dave Boyer likes to call frequent flyers, meaning they needed a lot of injections to get dry. And we did particularly well with this group, with essentially no change in the vision, 92% reduction in treatment burden, and 2/3 of the eyes were supplement-free up to six months.
This type of response to our drug brought out a new type of treatment paradigm that we believe will be how EYP-1901 is getting used. Remember, we're not advocating replacing all the large molecule IgG blockers for EYP-1901. We're positioning our drug as a potential maintenance therapy, suggesting that doctors can treat the wet AMD patients initially with any anti-VEGF of choice to reach the desired dry anatomy with best visual acuity outcome. Following that, maintain with our drug, with sustained delivery zero-order kinetics. If our phase I data holds through phase II and phase III, we believe that doctors would have the flexibility to take over half the wet AMD population out six months or longer with our drug alone.
However, some of the eyes will still need supplementation, and that's okay, provided we are giving the doctors and the patients a benefit of fewer injections. So again, this is all about flexibility for the retina specialist, tailor the dosing schedule to the patient needs and their desires, and the doctor's desires to see patients or inject patients as frequently as they like. But they can treat with a potentially complementary mechanism of action and treat these chronic patients with potentially just a long-acting drug, if necessary, but add to it short-acting in some cases. This can optimize the patient visits and patient flow in the clinic. So now let's move on to the phase II DAVIO 2 trial.
So we designed the phase II clinical trial to support the initiation of the phase III clinical trial programs, and this was all based on a type C meeting and some follow-up communications that we had with the FDA last year. The objective of the trial was to evaluate the efficacy and safety of a single injection of two doses of our drug, approximately 2 mg and approximately 3 mg, against an on-label Eylea control. We learned some things from the DAVIO trial, and one of the things we learned is that eyes that are failing standard of care, doesn't appear that we have a particular benefit for them, and therefore, we try to exclude patients who are clearly not responding to standard of care.
We did that by having a central subfield cutoff on OCT of 350 µm at the screening visit, immediately following a recent anti-VEGF. We also didn't allow patients who had significant intraretinal fluid to be enrolled, since we know this is a bad prognosis. We also changed the supplemental criteria a little bit in DAVIO 2. In particular, we added an additional supplement criteria. Patients who had a five-letter loss with 75 µm of new fluid were to receive a supplement or rescue injection. Other criteria was similar, 10-letter loss due to wet AMD, 100 µm of new fluid, two visits in a row, new hemorrhage from wet AMD, or of course, at the investigator discretion. The primary outcome in DAVIO 2 is a visual acuity outcome, just like it will be in the phase III trials.
The visual acuity is non-inferiority change in visual acuity against the Eylea control, and it's a blended endpoint. If measurement is made at day one, and then the visual acuities are blended between week 28 and week 32, and the difference is calculated. This slide shows the schematic for the study. Some things to note, everybody in the study was randomized at day one, and then everybody received a, aflibercept injection. At week 4, they were given a second aflibercept. At week eight, they were given a third aflibercept, and they then either received their real dose of EYP-1901 or a sham injection 30 minutes later. Patients then were followed monthly, and every other month, if they were randomized to the aflibercept arm, they received another on-label aflibercept. If they were randomized to the 1901 arms, they received another sham.
And again, primary endpoint was visual acuity change blended between week 28 and week 32. This trial was fully enrolled last spring with 160 patients. The last visit, 32-week visit, was earlier this week, and therefore, we are on target to release top-line data sometime the first week of December, ± a week. I want to summarize the entire safety for EYP-1901 with this slide. I talked already briefly about the phase I, but as of October 1st, 2023, we had treated approximately 173 patients with our drug in total. And this slide shows you the approximate numbers of DAVIO 2 and PAVIA. Of course, we don't know how the randomization went, so we can't give the exact numbers.
But with a minimum of four months follow-up after the EYP-1901 injection, there have been no drug-related ocular or drug-related systemic SAEs. And of course, most of those patients are a lot longer than four months out at October 1st. So we're very pleased so far with the safety profile. This demographic data was released over the summer. On the right is the pooled demographic data from DAVIO 2, and on the left is the demographic data from DAVIO, the phase I. Two things to note, it appears that we enrolled a relatively less severely treated group of wet AMD patients in DAVIO 2, which is what you'd expect. And you can ask our KOLs later, I think most clinical researchers aren't comfortable enrolling eyes that are doing really well in a phase I until they're comfortable with the safety.
So this is to be expected. But the other thing to note is the mean CST was quite a bit lower than in DAVIO 2 than it was in DAVIO 1, 265 µm versus 299 µm. What that suggests is this group of patients were under better control than the phase I. So now let's talk about potential outcomes and what they are and how we're viewing them. So recall that for a non-inferiority wet AMD trial, the FDA has defined the lower bound for non-inferiority as minus 4.45 letters. Which means whatever the difference is between the treatment arms and the control arms, the lower confidence limit can't cross - 4.5 letters. We've given some ranges for outcomes, and again, this is not expectations.
We don't know what the outcome is yet, but this is how we're looking at the potential outcomes for visual acuity. We think that if one or both of the EYP-1901 arms are no different than Eylea or numerically or even statistically superior to Eylea, this would just be a superior outcome for us. We think an outstanding outcome would be if one or both arms is between -1.4 letters and zero letter change to the Eylea control. Now, why did we pick -1.4? There was no science behind it. This was quite simply the difference between 8 mg or high-dose Eylea and 2 mg or standard Eylea was -1.4 letters.
Therefore, if we can equal that or better it or be in that range, but we're a Q six-month or longer drug, we believe that would be a really point to commercial success. We still feel that a difference of -1.5 to down to -2.9 would be a great result. In a patient in a group of patients with of a number of 160 and a very low standard deviation for the change in visual acuity, even a difference of -2.9 letters would be a potentially statistically non-inferior. Obviously, if we're worse than four letters, we're too close to that -4.5, and we'd need to do some subgroup analyses to try to figure out why and if there's anything we could do to improve the results.
And I will ask, the Dave and Dave team I've got here about how they feel about letter changes with more durability in just a moment. So how about the other outcomes? Again, we've talked about the most important ones already, which are safety and change in visual acuity, but what about the secondary outcomes? First of all, we put this as a floor. Again, these are not expectations, but these are what we consider the floor for these outcomes for us to really be confident in the program going forward. We'd like to see a floor of a 50% or better reduction in treatment burden, and we'd like to see 50% or better of the eyes going supplement-free up to six months. Remember, that figure was 53% in the phase I. And we want to see stable anatomic outcomes.
What that means is not a big increase in fluid on the OCTs in the treatment arms. The reason is that we could have a very good result in the supplement-free, but if the eyes were supplement-free, but they were all gaining fluid in the real world would have been supplemented, then that takes somewhat away from the result. So I can't say that one of these secondary outcomes is more important than another because they all are going together to show the clinicians how well our drug will perform as a maintenance therapy in wet AMD. Now, just about reduction in treatment burden, this has been traditionally measured in a way that I would call retrospective.
You take the number of injections that an eye received for the year or two-year period, going into the study, and then you compare them to a similar, normalized number of supplement injections that they received starting at week 12, which is the first time they could be supplemented. So that's the retrospective way to do it. We're also going to be able to assess treatment burden prospectively against the aflibercept control. Recall that after week 12, all the aflibercept control eyes should receive on average of at least three injections. So we'll be able to calculate a reduction in treatment burden against that as well. All right. I'd like now to reintroduce our two KOLs, David Boyer and David Lally, and have them enter the discussion here.
First of all, Dave Boyer, can you start out by just talking about your current clinical practice, where you're located? You know, are you in a academic group practice, multi-specialty? Talk a little bit, and for your case, I know it'd be hard to talk a little bit about your involvement in clinical trials, because you have been involved from the very start with just about every clinical trial in retina. And again, how about how much of your portion is dedicated to wet AMD? Go ahead, Dave Boyer.
Jay, thank you very much for allowing me to be here. I'm in a 10-person practice in Los Angeles. We cover a fairly large area. We have seven offices plus some satellites, and I've been involved in clinical trials since the HIV days and have participated, as Jay indicated, in virtually every wet AMD trial that has been done starting in phase I and II trials, all the way to post trials, phase IV trials. You know, one point I really wanted to stress here is, you know, a lot of people are asking, I think, why do you need that run-in? Why do you need, you know, to have aflibercept?
I think that, Jay, the one point I want to make is, if I have a drug that can last five months-six months, this would be a tremendous game changer. And it takes TKIs a while to get into the cell, and that's why you need something aboard to get rid of the VEGF that's present. But if you can duplicate what you did in the DAVIO 1, and I participated in that, it would be a game changer in my office. We have most of our trials right now are looking at trying to extend the time period between injections, and we've had two recent acceptances by the FDA, and basically, there's no visual improvement, but they do extend the time period between injections.
So I think that this fits right in with what's going on and may give us even a longer period than I'm currently seeing with the current drugs that I'm using that have been FDA approved.
Great. Well, well, thank you, David. You've really already cut to the denouement here and kind of summarized very nicely where we think we're positioned. Dave Lally, I'm gonna before I ask you the same question, I do, I do want to just make a little follow-up to Dave Boyer's point about the run-in. First of all, the run-in of Eylea that we are doing in the phase II and in the phase III was actually mandated by the FDA. The FDA told us that in the pivotal trials, we can't go right to every other month Eylea, because we don't know what the patients would have received going into the trial.
After you know that explanation, we asked the FDA, "Well, can we do a run-in with the EYP-1901 arms?" And they said, "Sure, go ahead." But the consequence of that is that we had to run the pivotal trial out one year as opposed to nine months. But we thought that was a fair trade-off in order to essentially level the playing field. Now, in reality, we don't really know how our drug would perform in an eye that still had VEGF in it, and we're not planning on testing that hypothesis in the phase III either. But I also, last point, I said this in my little talk, but I want to repeat it: We have pretty good animal data that says our drug, vorolanib, when it's delivered in Durasert E™ , is detectable in the tissue in 20 minutes.
and is at therapeutic levels in hours. So even though these, drugs work at the cellular level, at least in the case of EYP-1901, we believe that there is an immediate effect. Okay, Dave Lally, same question. Tell us about your current practice situation, who you're in practice with, your involvement in clinical trials, and how much of your practices is wet AMD.
Good morning, and thank you for having me. I work at a private practice in Western Massachusetts, in Springfield, Massachusetts. We're a group of four retina-only specialists, and we're the only retina-only group in all of Western Massachusetts. We serve over 1 million people. I've been out of ophthalmology training for about eight years now, and I have a strong interest in clinical trials, participating as a primary investigator and co-investigator in over 40 trials. Many of them have been for wet macular degeneration from phase I to phase III trials. I'd say about 40%-50% of my practice is the management and treatment of patients with wet macular degeneration. It's by far the most common patient I see in my office every day.
Great. So David Lally, when you see a new treatment, naive wet AMD patient, what's your current approach? And specifically, you know, do you go into a treat and extend? Does everybody get monthly, and how do you treat and extend patients?
Yeah. So I initiate our standard intravitreal anti-VEGF therapy, and I start with every four-week treatment with every patient until that patient is dry on the OCT picture. And however long that takes, once they're dry, I then start the treat and extend paradigm, where I typically extend by two-week intervals at a time. And I will continue extending out the interval, and, you know, what's the maximum interval I'll use? Well, it depends on the product. So, you know, our more traditional anti-VEGF therapies, like Eylea, Lucentis, Avastin, I feel comfortable going out to a three-month interval as the maximum interval. With our more recent medications, like Vabysmo or Eylea high dose, I'll extend out to potentially four months. But I usually typically give patients at least three monthly injections before I start that treat and extend paradigm.
Great. Dave Boyer, is that similar to what you do?
Yeah, it's virtually the same, except I will start to extend after the second injection. So they come in, they get an injection. Four weeks later, they get an injection. If they're dry, I usually go to six weeks, and I extend by two weeks.
You extend by two weeks. Do either of you ever extend by a month from the start, even with the new drugs, faricimab and 8 mg of aflibercept?
I haven't really, to be honest. I saw the results with these four-week extensions. I just feel that I'm not comfortable quite yet. I think there's a lot of hype of how long some of these drugs may last, and I have not seen that in my practice, that they can go four months in many cases.
Well, are either of you aware of any, what you call, good, maybe even retrospective clinical data? Like, in the real world, how many Vabysmo patients are going out three or four months in treat and extend? Do we have that data yet?
We have some payer data looking retrospectively of patients who were switched to Vabysmo and what types of treatment intervals they were able to ascertain compared to Eylea and other medications. And that data is very confounding, and it's very tough to analyze. So I don't think we have great data, to be honest, to really know.
Yeah. So let's just... Now that we've started to talk a little bit about new therapies in wet AMD, Dave Lally, can you give us an overview of when you get a new therapy, and how do you adopt it? And the second part of the question is, I'm gonna give you a list of things, and you tell me what's important to you in the adoption of a new therapy: safety, ease of administration, effect on vision, longer intervals, and the J-code. You're in private practice, that's important. So when you try to kind of synthesize all that together and say, we hand you a new treatment, how are you gonna integrate it into your practice?
Yeah, there's no question for me, the number one thing on that list would be safety. Why? Because we currently already have very safe and effective treatments for wet AMD. Anti-VEGF therapies work great for the majority of our patients. The problem is, they wear off quickly, and these patients are coming back to the clinic. But they work well, and they're safe. So number one, with any new therapy, it's safety, especially with the recent FDA approvals of some other recent medications, where we've seen safety issues in the real world. So I wanna see safety in the clinical trials, and I also wanna see that safety in the real world.
You know, in terms of the second thing, you know, it would be J-code, to be honest, and J-codes really will hamper us in terms of using therapies until that J-code is received. And then from there, it goes to the point of, you know, what's the mechanism of action? How much longer of an interval do I think I could get this patient? And if I have a patient who's been stuck at every four weeks for a long time, and this therapy shows me it really has a good chance of getting that patient a much longer to 12 weeks or 16 weeks, and there's not a J-code, I still may try to fight for a way to get that medicine to that patient sooner.
But it would go in that order: safety, J-code, and then how much longer of an interval.
Right. Dave Boyer? How do you feel about adopting a new treatment? What's important to you?
Well, I think safety, as Dave Lally pointed out, is, is the number one. I mean, we've had accepted treatments that when, went out in, into the real world, showed that there was a safety signal. So I think safety is, is very, very important. It's the number one thing for me. Number two, for me, it, it would be the, how long can I extend these patients? The reason I say that is, you know, I have patients that have to come in every four weeks and five weeks on current therapies that theoretically should go eight weeks, like, aflibercept.
And if you can take that four-weeker and make them an eight-weeker, which is not, you know, without just doubling the time between, that reduces their number of times they have to come into the office by 50%. So I think you'll get some of the four-weekers up to eight and 10 weeks. You're not gonna get these very, very difficult to treat patients out. I don't think to three months or four months, but no drug is doing that right now. We've seen failures because people didn't realize there was 15%-20% of patients that just require constant injections. But with the long-acting treatment of a TKI, I think that you have that ability possibly to have chronic drug aboard and to change the milieu in the eye, possibly get an extension.
Then, of course, the J-code, we all want to get paid for what we do. But if you do Medicare patients, and it's been FDA approved, you usually will get paid. But certainly, I'd like the confidence to have a J-code for somebody's very expensive drugs.
Dave Boyer, would it bother you if some of your patients who are every four weeks could go out to eight or 12 weeks, but it would require alternating the drug, alternating the TKI, like EYP-1901, with a standard anti-VEGF to get there? Does that concept have any problem for you?
No. I mean, I think that, you know, the biggest problem that we have is the patients coming in, spending an hour and a half in my clinic to get that injection. Most of the time, you know, they have to bring someone in. They have to have a driver. No, if I could extend them with whatever method, I mean, let's say that you could go six months with 1 injection, and I have to supplement them at three months, not a problem at all. Or I think reducing the number of treatments for the patient is extremely important. If you ask the patients what order they want, extension would be number one for them. I don't think they realize the potential and then probably safety. So it's a different paradigm.
They're very concerned about, "Can you extend me, doctor?" That's the question I get asked all the time in my office.
Right. And so both of you quickly on this question, how convenient is it to have a treatment option that's in preloaded, sterile, and stored at room temperature?
To me, it's very important. You know, it sounds crazy, but storing something at room temperature makes it... It's a big difference because we only have so much room for anti-VEGFs in our refrigerators. We're buying new refrigerators, but we don't have the space. Preloaded makes it very, very easy to administer. So I think that, you know, those are really big pluses. I mean, even the small thing, going from a vial to a syringe takes time, and there is a risk of breaking sterility and increasing the risk of infection. So if you can store it, you know, without being refrigerated, that's a big thing.
If you just open it up and able to treat immediately, I think the sterility and the lack of time to mix a drug or get it ready is a very big thing in our office. We do, you know, probably 30 injections a day. I do 30 injections a day. I don't know what my partners do.
Mm.
But even five minutes, you know, between them, that's a lot of time that's spent making drugs available.
Great. So now I want to move on to the potential DAVIO 2 results and get your comments on the potential outcomes. So I'm gonna pull this slide back up to show you these ranges again. And Dave Lally, what do you think about these ranges that we've thrown out here? Do you agree? Would you think the wording should be different on any of those descriptions?
Yeah, no, I think, I think, you know, I think you're right on the money. I, I agree as well. I mean, for me, you know, vision, vision is the path to regulatory approval, vision change. But when I'm looking at this data, I mean, I look at the vision in context with the changes in CST and within the context of when, and if supplemental injections were given. Because, you know, if, if it's right before that primary endpoint, that blended endpoint, and a lot of patients are getting supplemental injections the month before, you know, that, that likely will boost their vision right at that blended endpoint, time point. But the counter is true as well, you know.
If there's patients that the drug effect is starting to wear off, EYP's effect is starting to wear off around that six months, but they don't meet supplemental criteria, and their CSTs are starting to get thicker, and they're starting to drop a few more letters, I'm okay with that. So for me, it's, you know, anything less than four letters, I think is within the ballpark of this drug's working and lasting for that durable six-month period.
Right. Dave Boyer, how do you feel about that? Kind of how much durability are you willing to trade off for vision or the other way around, let's say? If you have more durability with a safe drug, would you give up three or four letters?
... I certainly would give up three letters, two - three letters, because there's a tremendous amount of variability just in taking visions in general. I certainly would be happy to have less injections, less chance for complications, endophthalmitis, for two - three letters difference. You know, as you pointed out very aptly, the difference between high dose and aflibercept and the conventional 2 mg was, you know, a little over 1.5, about 1.2 letters. So, you know, another letter to two - three doesn't really bother me. I think having something aboard that constantly liberates medication is gonna change how we view these patients and how we treat them. So I would be happy to give up a couple letters for longer durability.
And, give me your thoughts about Home OCT helping with this. Not just now, but really put your crystal ball on and tell me in a couple of years, do you think Home OCT is gonna be helping us with this? David Boyer?
It'll be a game changer if we really had the ability to have a Home OCT. It would allow us to do PRN or as-needed treatment based upon the OCT. The early studies of small numbers, of course, are really showing the ability to pick up the fluid early and then have them come in right away. It'll change how we do our clinics. You're gonna have to have a set amount of patients slots that we would have to be able to bring them in within a few days to be able to treat them, but I think it will be a game changer. I think these type of long-acting delivery systems will make a huge difference in how we treat these patients.
David Lally, on this slide, again, we threw up a number of 50% of eyes or better, we'd like to see supplement-free up to six months. How do you feel about that? What are you looking for, for the supplement-free number?
Yeah, that's exactly around the number I'm looking for, is half the patients can go six months. Why? Well, it's just, you know, current right now, it's we have Vabysmo and Eylea HD showing us that about half the patients can go four months. So if we're looking at more durability compared to those two products as the new benchmark in terms of durability, you know, to me, it's like you got to go at least two months longer than four months, you know-
Mm-hmm.
To month six. And if we're going to six months, and half the patients are injection-free, that's a huge game changer. Because, again, the average patient in my clinic does get 6 injections a year, is stuck at every eight-week intervals. So if you can get that patient from six shots a year to two shots a year, that's a huge benefit for that patient.
So let me throw out a theoretical. How about three shots a year? But let me explain what I mean by that. We've talked a lot about patients who have zero supplements up to six months, but when you allow that number to be zero or one supplement, in DAVIO phase I, we had 80% of the patients got up to six months with z ero or one supplement. If that were to hold through the phase III into commercial, that we were able to take half the population with zero supplements and another 30% with an average of one supplement a year, basically, we could tell the retina community that we can take 80% of the wet AMD population with an average of three injections a year. Some getting two, EYP-1901, some getting four, EYP-1901 with two supplements. Does that resonate with you?
Absolutely, yeah, because that's a large majority of our patients. And like I said, the majority of our patients currently are stuck around that 8-week interval. So if they now are getting three shots over six months with one... Or you're saying 30% are getting one rescue-
Yes.
That, to me, are the tougher to treat eyes. So that might be the four-eight week interval patients that you're now getting them out to three, three shots or two shots over those six months. That's a huge - that's still a significant reduction in treatment burden. I mean, I typically find that any patient I can get out to 12 weeks or longer, those patients come back to the office, they don't feel like they were in my office yesterday.
Mm.
It's those patients that are stuck at the eight-week interval or less, they feel like they were just in my office, and they have this anxiety every time they're coming in, leading up to the exam. So if you can get the majority of my patients out to three months or greater, that's a huge benefit for my practice.
Yeah, I used to joke: it's like the what's new question when he asked the patient, "So what's new?" And they say, "Doc, you just saw me a month ago. There's nothing new.
Yeah.
Dave Boyer, what do you think about that idea of z ero or one , 80% of the population? Is that something that you feel also is gonna be helpful? Doesn't have to be zero.
Oh, I agree with Dave Lally. I, that's a game changer in my practice. I have a lot of patients that I can't get beyond six weeks.
In a moment, we're gonna open it up to some analyst questions for us. But Dave Boyer, I'm gonna give you the last word here, which, you know, we're talking really just about wet AMD, but if EYP-1901 proves positive in wet AMD, what do you think about read-through for other indications like NPDR and DME?
I think that's really... That would be phenomenal. Those patients, if you could have a long-acting drug for our diabetic patients, these are people who, unfortunately, get sick, they lose their insurance, and they can't come in, and the results, as you indicated earlier, are disastrous when patients don't come in to receive treatment, as needed... So I think that this drug should work in diabetes and diabetic macular edema. I think it can work in other vascular conditions where there's leakage. So I think that changing the milieu in the eye with these long-acting drugs, I think that this would be a game changer for the diabetic population. They would need much less injections, which is great.
Sure.
Because they're going to doctors very frequently, and reducing that number would be great.
Great. And so Operator, if we can now open it up to the audience, if they have any questions.
Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.
Hey, guys. Thanks for the presentation, and Dr. Boyer and Dr. Lally, good to hear from you. Thanks for the time. Just to put a finer point on expectations, assuming that the DAVIO 2 trial is successful and the data are replicated in the phase III, how would your use of EYP-1901 change based upon the two scenarios, with one being a -1 letter or better result versus Eylea, and the other being a minus 2.5 letters versus Eylea?
Thanks, Tyler, for the question. David Lally, did you want to answer that first?
Sure. Yeah. I mean, I would say personally, for me, it would literally mean no difference to me, Tyler. And again, that's because to me, visual acuity, there's a lot of confounding things that I think about when I look at these visual acuity results. And I have to, in my mind, put it into the context of what was happening with the CST at that endpoint time point, and what was happening with supplemental injections, you know, going on right before that time point in relationship to the supplement treatment retreatment criteria. So I'm not even really thinking of that at all, to be honest.
David Boyer, all things being equal, do you think there's any real difference between a one letter and a two-letter difference as a result?
No, I don't. The visions vary, you know, depending on dryness and the patient and the technician actually even taking the visions that day. You know, I agree with Dr. Lally. I would be looking at the OCT very carefully, and the patient could come in and may have lost two or three letters, and if the OCT is dry, I would consider that patient doing well. I don't think, you know, two or three letters in our office can fluctuate from morning to the afternoon. So I don't think that's a big difference. You know, if you get beyond that, you know, to five letters, that is a difference, but two or three letters doesn't change my mind.
Great. Thanks, Tyler.
And maybe just one more, if I may, for Dr. Boyer and Dr. Lally. What percent of patients would you put on extended-release TKI with this profile if it makes it to market? And would it be used as a maintenance therapy, and how would you decide who to put on one?
David Boyer, you want to take that one first?
Yeah, you know, as was pointed out, I think that it probably would start as a maintenance therapy, and when you introduce it, would start to change as you feel more comfortable. You know, the trial is going to show that you're going to get three basic Eylea injections, but we may find that maybe you only need one or two . And that's something that, unfortunately, as I've indicated at meetings, retinal specialists are dyslexic, we can't read labels. So you try to figure something out that we think is better for the patient. So I think I would probably start as using it as a maintenance therapy, just meaning that I would start with an anti-VEGF.
I don't know, in private practice, if it would require one injection and give the drug two weeks later, or give a multiple, two or three injections. But I think I would start the patient probably as a maintenance therapy.
But, regardless, David, do you think that alters the utility of the drug, whether you choose to give one Anti-VEGF at the start or two or three?
No, I think, you know, based upon, you know, the pharmacodynamics of this drug, you may be able to get by with 1 injection of an Anti-VEGF and start your medication early. Perhaps you need two, but you may not. Certainly, it will give you an idea of how sensitive the patient is to treatment. You don't want a patient that you give an injection and nothing happens. That patient's probably not going to do very well on almost anything that we have today. And we do have patients like that. So, I think that as far as starting it as an initial treatment, I'd have to see how fast the drug reacts and works, because I don't want to leave any fluid on the OCT for a month or six weeks.
It'll be, in private practice, I probably would start just to do it as a maintenance drug.
Great. Next question?
Please stand by for the next question. The next question comes from Eddie Hickman with Guggenheim Securities. Your line is open.
Hey, good morning, guys. Thanks for hosting the event. I wanted to ask both of the doctors on the call how they think about reinjection data for EYP-1901 and how important it is than to see safety and/or efficacy data if they plan to use this as a six-month treatment in the long term going forward? Thanks.
... Dave Lally, you want to talk about reinjection and how you view it, safety, efficacy, long term?
Yeah, yeah. So I think in talking about reinjection, you have to start. I have to start with, well, what did we see in the DAVIO 1 trial? You know, we put in a few. Some of these higher doses had three implants that were put in the eye. And initially I was thinking: Oh, man, these patients might see these implants. But we literally saw no patients visualize these three implants. They really do sink to the bottom of the vitreous. And we had a few patients in DAVIO 1, and none of them had any visual complaints of seeing the implant. So that to me was a huge, you know, it was a really encouraging thing for me to see.
I think it's also nice that these implants fully, you know, or have been redesigned with the Durasert E™ to fully bio, you know, erode over time. So now I think of it like an Ozurdex in my head, which is one that I use in practice every day. And I certainly have lots of patients in my practice that I treat with Ozurdex every three to six months, over and over and over for years. And those implants, they go away, and there's no problem with reinjecting these implants. Regardless of whether it's a 22-gauge needle or a 25-gauge needle, you know, these patients do fine with repeat injections. So, you know, I have no concern about the retreatment. But yeah, safety to me is going to be critically important for a long-acting therapy. You know, we want these therapies to be safe.
You know, one thing we didn't really talk about yet is I really see another population of these patients would be the elderly, the really older patients with wet AMD, you know, that are coming in even every three or four months, only having three or four shots a year. They often miss appointments to see me because they have other medical health issues. Boy, would it be nice to have an implant like this in, that's delivering therapy when they can't see me on interval, and they're coming back a month or two or three months later because they were in the hospital. I do feel a little more reassured knowing that there's some drug still on board in their eye, hopefully protecting them to some degree as compared to another medicine that did not have that durability.
Great. David Boyer, do you want to add anything, reinjection safety?
Reinjections of the drug doesn't really bother me at all. You know, I had the same experience. We had patients with three inserts without any signs of a problem. So reinjecting, I don't think is going to be a major problem at all. But I agree with Dr. Lally.
Great. Thanks, Eddie. Any-
Thanks.
More questions out there?
Okay, please stand by for the next question. The next question comes from Jennifer Kim with Cantor Fitzgerald. Your line's open.
Hi, guys. Thanks for the presentations, and thanks, Dr. Boyer and Dr. Lally. My first question is, I'm just thinking about how doctors look to get patients dry and the potential for Home OCT and all of these different factors. And I'm wondering, how do you think the idea of a sustained constant delivery of drug to the eye changes the way you assess OCT in your patients?
Dave Boyer, for sustained release, do you feel like we need to think about fluid buildup any differently?
I think that's a great question, and I'm glad that they brought it up. When you have a sustained release drug, you're much more tolerant of a little bit of fluid. You may want to see that patient back in two or four weeks because, as you know, it was pointed out, this is a chronic release, and there's some little variability even on the OCT. You know, we hold it as the holy grail, but there can be some slight variations. And with this drug and other longer-acting drugs, you might see a little bit of fluid, and then the next time they come in, it's totally gone. So that's a great question.
I think that Home OCT would certainly give us the opportunity to be able to follow that, and if it's not just one time that we start to see an increase, but it continues to increase over the week period, then we would definitely be able to call them in. So it would be a game changer. But you're absolutely correct. When you have a long-acting delivery system, as we have, you don't have to worry about slight fluctuations, because the medicine's aboard for a long, long time. So it's unlike a bolus injection of an anti-VEGF. When you start to lose that effect, it doesn't come back. You've got to treat them at that point. This is a totally different way of looking at the OCT in our patients in general.
Dave Lally, you have anything to add?
Yeah, I would just add, I think looking at the—like the change in the CST amplitudes over time is going to be interesting, kind of what people are looking at right now with Iluvien, with DME. With this longer-acting therapy, you know, when we typically bolus eyes with our anti-VEGF, the retina goes from being very swollen to not swollen, and then the drug wears off, it becomes swollen again. So it's like the retina is yo-yoing back and forth, is the path of the patient over time. And can this type of therapy keep that yo-yoing amplitude to a minimum? And if it can, what kind of visual changes or benefits can we see long term because you've kept that process from occurring?
David, what kind of amplitude for the yo-yo is acceptable to you in wet AMD? Do we have any data on that?
I have no idea. I mean, I don't think we know, but I think just, you know, intuitively, it makes sense that the retina wants to be dry without fluid. So you know, if it intuitively makes sense that the, the natural state of the retina is without fluid, then you can intuitively think the more fluid that's, you know, coming and going fast would be a bad thing for the retina. But again, that has to be proven. And I think with Home OCT, we're going to figure that out, that question out over time.
Dave Boyer, does subretinal fluid mean something different to you than intraretinal fluid?
... Yeah, I think that intraretinal fluid is much more dangerous or causes more visual deficit than subretinal fluid, especially in the wet AMD population. So it does matter where the fluid spaces are. If it's subretinal, probably willing to tolerate a little bit. If it's intraretinal, then we try to get rid of that as soon as we can.
Terrific. Can we go to the next question, please?
Please stand by for the next question. The next question comes from Colleen Kusy with Baird. Your line is open.
Hi, good morning. Thanks for hosting the event, and thanks for taking our question. So for Dr. Lally and Dr. Boyer, can you speak to how you normally decide to retreat with Vabysmo? Is it visual acuity or fluid that you normally decide on? And if fluid, how much fluid do you normally tolerate before retreating?
David Boyer, want to take that first?
Yeah, I think that we don't tolerate much fluid when you give a bolus injection, because we know that once you start to develop additional fluid, the drug is wearing off, the drug effect is wearing off. So any intraretinal fluid that I would see, I would definitely treat. Subretinal fluid depends, you know, how much and where it is. We try to keep these retinas as dry as possible, so there's no magic number that I can say, well, 20 µm difference or 25 µm difference would force me to treat. I think what it's based upon is what the previous OCTs look like and what it's looked like going forward with a bolus injection at this time.
If I start to see fluid reaccumulate, even if it's just a minimal amount of thickening, and the vision many times is the same as far as the patient's concerned, I would retreat that patient, because the medicine's wearing off.
Dave Lally, how do you approach that?
Yeah, I agree with Dr. Boyer. I think certainly with intraretinal fluid, we want to get rid of all intraretinal fluid and keep it away. I think the story with permitting or not permitting subretinal fluid is a dynamic story. If you were to ask me a couple of years ago, I would have said a little bit of subretinal fluid may be okay, you know, based on some post hoc analyses from some studies, where patients with a little subretinal fluid a year out had actually better visual acuity. But, but there is more, some recent data that that's not necessarily true, and there may be confounding reasons for that. So, you know, my current practice, I will tolerate a little bit of subretinal fluid. What's a little bit? That's hard to characterize, like Dr. Boyer said. It's kind of like you know it when you see it.
I will tolerate it as long as the vision is staying stable. There are some cases where I've had patients with a little subretinal fluid. I've been treating at the same interval, 6-week interval, for a long time, and then all of a sudden, the visual acuity starts to go down. That makes me nervous. So really it's treating based on OCT. Unless patient has a little bit of fluid and their vision starts to decline, then I bring vision into it.
Is your observation, Dave Lally, that when patients have new fluid, they notice it and they complain of it?
I mean, it's interesting, you know, you know, anecdotally, some patients who have subretinal fluid, you know, think they're seeing better. You know, some think they're seeing worse, and others think they're not seeing any different. I see the gamut of that. With intraretinal fluid, they're typically complaining it's a little bit worse or they're just not picking up on it. But yeah, I think we just don't know enough about subretinal fluid at this point. So the current standard of paradigm is to try to keep the retina as dry as possible.
Great. Next question, please.
Please stand by for the next question. The next question comes from Richard Wang with Mizuho. Your line is open.
Thank you for the team for taking my questions, and, great presentation. So my question goes to both Dr. Boyer and Dr. Lally, and thanks again for, you know, being here and presenting on this. So of your patients, in the first year, assuming positive data and 1901 is launched, in the first year, how many patients would you think would you start out with? So, this goes back to the first question on the call. Is it more like 30% of your patients, or 50%, or like all your patients will go on therapy? And then as your, as your usage and experience increases, and let's say, you know, at, you know, any peak time, how many patients do you think would be on 1901? Thanks for the question.
David Boyer, why don't you go first on this one?
Yeah, I think that, we would certainly, in my practice, I would treat all the patients that are under eight weeks, in the beginning to see the response. By eight weeks, I mean, that I'm treating every eight weeks or less. And that's a fair number of patients. In my practice, that probably may be 30-40% of my patients go eight weeks or less. And then I would probably, depending on the results, if the results are able to extend some of these four- and six-weekers to 10 weeks, without additional reinjection, I certainly would start using it more and more. So, you know, I think most retinal specialists would start slowly and treat the more difficult to treat patients, assuming that we do get a response.
You don't want to treat eyes that aren't responding to anything at all. But, the ones that will be dry at six weeks or eight, or seven weeks or eight weeks, you may be able to get those people out to 12 weeks, and that would be a big savings to the patient. So I would start there, and that's probably 30% of my patients. A year later, you know, I would start treating patients at, let's say, go 12 weeks, and if I can make those 12 weekers six months, that would be phenomenal. So I think that the use, as we become more familiar with the drug and how it works and the response we're getting, that the number will increase.
I would say that probably in the beginning, 20%-30% of my patients would fit into the category that I'd try to start them on this type of treatment.
David Lally, final words.
Yeah, I would just agree with Dr. Boyer, you know, starting with those frequent treaters, eight weeks or less. But I would also add to that, I would also consider patients, again, who are very elderly, so they're 85 or older. It's really hard to get to the office, lots of comorbidities. They may only be coming in with for anti-VEGF every or four months, but again, I can't rely that I'm going to see them back at that interval. So I think putting a product like this in might give, give me a little more confidence that if they miss their interval, they'll be okay.
Well, thank you. And with all we have time for today, I hope you've enjoyed this as much as I have, and I really want to thank East Coast Dave and West Coast Dave for taking the time to do this, and thank you all for your attention, and have a great day.
This concludes today's conference call. Thank you for participating. You may now disconnect.