Thank you for joining the EyePoint Pharmaceuticals presentation on day three of the J.P. Morgan Healthcare Conference. I'm Wan Heo from the J.P. Morgan Healthcare Investment Banking team, and it's my pleasure to be introducing you to Dr. Jay Duker, President and Chief Executive Officer of EyePoint Pharmaceuticals.
Thank you very much, and thanks all for coming and listening this morning. We are a publicly traded company, and as such, I'll be making some forward-looking statements, and if you need any more information on that, please feel free to visit our website. EyePoint, as it in its heart, is a drug delivery company to the back of the eye. Our lead product is called EYP-1901. It's a combination of vorolanib, which is a small molecule tyrosine kinase inhibitor that has activity against all the VEGF receptors, and it's placed into our patented Durasert E™ delivery system. E is for erodible. This form of Durasert is completely bioerodible. We will have recently reported very positive top-line phase 2 data in wet AMD, which I'll be reviewing for you this morning.
We plan on initiating the first wet AMD phase 3 trial in the second half of this year, and, we also have now two other phase 2 trials ongoing. The first is called, the PAVIA trial, which is non-proliferative diabetic retinopathy, and we are on target to release top-line data from that trial in the second quarter of 2024. And just this morning, we announced dosing the first patient in our third phase 2 trial, which is called the VERONA trial, and that's for diabetic macular edema or DME. We would expect to have the top-line data from that trial in about a year. In the past few months, we announced a new, addition to our pipeline, EYP-2301.
This is a combination of the small molecule razuprotafib, formerly known as AKB-9778, and we were able to place it in our Durasert® E inserts for extended duration release. This is a Tie2 agonist, which should help stabilize the retinal vasculature in serious retinal diseases. Durasert is our patented delivery system. Durasert in its non-erodible form has been FDA approved in four products. There's tens of thousands of patients around the world who have had a Durasert placed. There's a very good safety and efficacy profile. In addition, the company now boasts a very strong balance sheet. We had a successful equity raise approximately a month ago, $230 million, and as of December thirty-first, 2023, we have over $330 million in cash and investments.
This gives us a cash runway through top-line data from these two Phase 3 wet AMD trials that I mentioned. This is our pipeline. Mentioned it already. The first three targets are all VEGF-mediated diseases for which we're applying EYP-1901. Talked about EYP-2301, and we are also working on putting some GA, Geographic Atrophy complement targets into our delivery system. Durasert is quite tiny. You can see one of our non-erodible forms on the left. The list of previous products that are FDA approved and have subsequently been licensed out include YUTIQ, ILUVIEN, Retisert, and Vitrasert. How we made this bioerodible is actually quite simple.
When you have a highly soluble drug, if you want extended release, you need to slow down the release rate, and we were able to do that by covering the matrix of the drug with a polyimide shell, which is completely insoluble. By removing the polyimide shell, we're able to have the core drug matrix release more rapidly, and in the case of EYP-1901, we believe we'll get therapeutic levels of vorolanib for approximately nine months in humans. The matrix of Durasert E™ takes several more months to bioerode after the drug release is done. Vorolanib really met all our criteria for essentially the perfect tyrosine kinase inhibitor to put in Durasert. It is selective, meaning reduced off-target. It fits very well into our Durasert insert. It has great patent protection out to 2037, which potentially could be extended to 2042.
In addition, vorolanib had previously been studied as an oral agent in wet AMD. At the time, it had the name X-82. While it showed very promising efficacy through phase II, because of systemic side effects, the program was discontinued. I'd want to note, however, in those phase I and phase II programs, there were no ocular SAEs mentioned. Vorolanib should also block PDGF, which theoretically would lead to an antifibrotic benefit, and we recently reported a preclinical study in rodent, which suggested that vorolanib may be neuroprotective. Vorolanib at therapeutic doses does not inhibit Tie2, which should help with clinical results. EYP-1901, again, is vorolanib in Durasert E™. This is delivered intravitreally in a standard way that all the other anti-VEGF agents are, local anesthesia in the physician's office.
This comes in a preloaded injection system, and within the injection system, we can load up to three inserts, so we can deliver three inserts with a single injection. Our drug is immediately bioavailable. In animals, we can detect drug levels in the cord within minutes after intravitreal injection, and it reaches therapeutic levels within hours. It features what's called zero-order kinetics, which means after reaching a steady state in approximately three weeks, you get the same release every day, every week, every month for approximately nine months. This zero-order kinetics allows what's been called microdosing, which is doses of the drug at what may seem to be less than therapeutic levels, can be very effective.
For example, our YUTIQ insert contains only 0.18 milligrams of fluocinolone, yet can control uveitis in 60% of patients for up to three years with a single injection. We have positive efficacy data in wet AMD now from both a phase 1 and a phase 2 trial, and ongoing safety data from two phase 2s and that phase 1 trial. Another differentiator for our drug is it can be shipped and stored at ambient temperatures. All the other anti-VEGFs need to be refrigerated. And you can imagine in a retina specialist office right now, the refrigerators have to be quite large because there's a lot of them out there. So the phase 2 study was called the DAVIO 2 study. This is a non-inferiority trial comparing two doses of our drug against an on-label aflibercept control.
The design of the study dates back to a Type C meeting that we had with the FDA in 2022. At the time, we were contemplating going directly from phase 1 to a pivotal trial, so we submitted a pivotal protocol and a statistics package to the FDA. There were comments, we made some changes, and at the end of the communication, the FDA had no further comments. We strategically decided to do a more typical phase 2 trial, but we took the learnings from the Type C meeting and applied them to our phase 2. And so the phase 2 trial design that we initiated as the DAVIO 2 trial is really a result of the Type C meeting. A couple of differences which we'll, I'll go into.
In all of these trials, because these are new drug entities, we need to allow for what's called rescue or supplementation of the patients. So if certain criteria are met so that the AMD appears to be out of control, the doctor is allowed to give a supplemental injection. In this trial, that was aflibercept. You can see the supplement criteria right there. This is fairly standard, although one thing we added compared to the phase 1 trial was the top bullet, five-letter loss with 75 microns of new fluid. This is a pretty tight control for supplement, and while we wanted to do that to make sure the primary endpoint, which is non-inferior visual acuity, was met, theoretically, it may have led to an increased number of supplements, but as you'll see in the results, it didn't do that.
The primary outcome for this study was change in visual acuity from day 1 to a blended week 28 and week 32 endpoint. The reason we blend the endpoint is because the FDA asked us to. In the pivotal trial, it will be a blended endpoint as well. The non-inferiority margin for this trial was -4.5 letters, and that's, again, what's been stated to us and publicly by the FDA for wet AMD non-inferiority trials. There are other secondary endpoints which we look at as well. This is the study design. There's a couple unique things about it. First of all, all the patients received a reload of aflibercept at the beginning of the study.
So on day one, week four, week eight, all patients received an aflibercept injection, and then 30 minutes later, at the same visit, they either received their dose of EYP-1901 or a sham. They were then watched monthly. In every other month, the eyes that were assigned to the aflibercept arm received another aflibercept, while the EYP-1901 eyes were received a sham. All three groups were subjected to the same supplement criteria, and therefore, this ended up being the first trial that actually had supplements in the aflibercept arm. This is a top-line baseline characteristics from the trial. Reading across, again, the aflibercept at 2 milligram dose, EYP-1901 at 2 milligrams, which is two inserts, EYP-1901 at 3 milligrams, the high dose, that was three inserts.
As you read across, you can see it's very well-balanced. The bottom line shows you the mean number of injections that the patients received in the year leading into the trial, and this was normalized. So, for example, if a patient only had wet macular degeneration for three months and received three injections, their normalized number of injections was 12. And the real world, on average, in the United States, doctors give about six injections a year. So these numbers, I would argue, possibly overinflate the previous treatment rate, but you can see this is a pretty heavily pretreated group with on average, 10 injections prior. This is a summary of the top-line results. We achieved all endpoints, and in particular, the primary endpoint of non-inferior visual acuity was achieved. The 2-milligram dose was minus 0.3 letters worse than Eylea.
The 3 milligram was -0.4 letters worse than Eylea. Remember, on the eye chart, there's five letters to a line, so this is less than half a letter difference. Statistically, if you apply statistical analyses to these groups with paired statistics, the p-value for these being the same was 0.0009. In other words, the three visual acuity results were essentially statistically identical. There were no EYP-1901-related ocular or systemic SAEs, and reduction in treatment burden in the first numbers mean how many injections did the patients get leading in versus how many injections the patients get after we gave them EYP-1901.
You can see significant reduction in this historical measure, but we also measured it prospectively, meaning the EYP-1901 arms against the mandated Eylea, and again, a very, very nice reduction in the treatment burden. The other secondary outcome was about two-thirds of the patients could go up to six months without a supplement. And the last anatomic control refers to measurements on optical coherence tomography or OCT. If you're not familiar with that test, think of it as an ultrasound using light. We do this in the office. It's quick, it's non-invasive, and it's a measurement of the thickness of the center of the retina. Normally, it's up to about 280 microns. The standard deviation is about 10 microns. And if you get an excess of VEGF in the eye, you get additional thickening of the retina.
It's a biomarker that we use to measure VEGF activity.... Again, this is top-line result, a reading across the top. Notice that all three arms gained about a letter of vision during the study. The reason primarily for that, as you'll see, was the load, the three injections that were given at the beginning. So one could argue that as a group, these eyes were probably slightly undertreated, but a change in one letter is noise. Patients wouldn't notice it, and a doctor or retinal physician wouldn't make a big deal about one letter improvement. Difference from the aflibercept I mentioned, this was 95% confidence interval that we achieved statistical significance. And the non-inferiority margin is -4.5 letters for wet AMD.
What that means is, our drug compared to the control, there's confidence intervals around the vision of our drug, and the lower limit of the confidence interval can't cross minus 4.5 letters. In this trial, for both arms of our drug, the lower limit of the confidence interval didn't cross minus three letters. So we were nowhere near the cutoff for the confidence interval, telling us a very tight statistical result. This is a graphic representation of the visual acuities. Notice in the first few months, all the groups improve a little bit. That's from the load. And then there's some bouncing around, which you're gonna see for its random nature, but really, they all hover about one letter at the end. This is on a scale of five letters, and again, five letters to a line of vision.
And so you can see at the end there, all three of the colored dots are almost superimposed. From a safety perspective, we've seen no reports of EYP-1901-related ocular or systemic SAEs. As of the data cutoff, we had four ocular SAEs reported in a study eye, but none were deemed related to our drug. Of the AEs, over 97% were mild, Grade one or Grade two, and most of them were the type of AE you would expect from an intravitreal injection. Things like a subconjunctival hemorrhage, a bleed in the white of the eye, irritation to the eye, or floaters. We had no insert migration into the anterior chamber. We wouldn't expect to see that. We don't see that with other forms of Durasert, but that's something that has been a problem for some of our competitors, so we make a note of that.
And of course, in the retinal space right now, everybody's a little bit nervous about Retinal Occlusive Vasculitis. We didn't see that either, nor should we. The matrix that holds our vorolanib together has been used in tens of thousands of eyes. There's nothing in that matrix which has ever been recorded to cause inflammation. And vorolanib is a small molecule, it's not a biologic, and there's no reason to believe that these small molecules would lead to this type of problem. We also featured actually really low patient discontinuation rate. On average, in wet AMD trials, the discontinuation rate is about 10%. Ours was 4%, and none of them were related to our drug. So I wanted to go through the four ocular SAEs that were reported in the study eyes.
The first was a retinal detachment that occurred one week into the trial, so one week after the initial aflibercept injection. There was no drug. Our drug was not in that eye. That was repaired surgically, and that eye exited the study. We had a case of bacterial endophthalmitis that occurred at week 32, so approximately four months after our drug went in, and this occurred two days after an anterior chamber paracentesis. This is an office procedure where we stick a small needle into the front of the eye to take some fluid out to measure the PK of vorolanib. This patient happened to be on CPAP, and CPAP is a known risk factor for bacterial endophthalmitis after an invasive procedure.
And this patient, actually, we cultured Serratia out of the eye, which is a very unusual bug for endophthalmitis and one that would be associated with CPAP. Interestingly, the patient did very well and recovered vision fully. We had a case of non-infectious, mild endophthalmitis, which occurred at week 29, again, seven days after an aflibercept injection. That also cleared completely. There was a case of retinal tears in an eye that occurred at week 36, four weeks after an aflibercept injection, and that was in an aflibercept arm. This is a table of the AEs, again, generally mild and self-limiting. Across the top, you can see on a percentage basis, there were more ocular AEs in the two treatment arms. However, when you drill down and say, what was the reason, you can look at the top three. First of all, worsening AMD.
In the trial, about a third of the eyes in the 1901 arms required supplement. That's worsening AMD, and that's something that the doctor decides it's either there or not there. Only three of the eyes in the aflibercept arm required rescue. That's the difference. Subconjunctival hemorrhage, I talked about, it's really something that occurs after any intravitreal injection, and it's of no consequence. And there were some cases of vitreous floaters, more in the 1901 eyes than in the control, and those generally occurred right after the inserts went in and generally were self-limiting. Just to level set here, this slide shows you the percentages of ocular AEs in phase 2 from both Vabysmo and high-dose Eylea.
So you can see ballpark, it's all about, you know, the same running between, you know, 40%-50%. I will say in the Eylea HD study, they only reported treatment-emergent AEs. They didn't report all of them. So in the way we reported it, those-- if they reported the same way, it might have been a little bit higher. In summary, about the safety, we've treated now about 170 patients with our drug, and we have no ocular or systemic SAEs related to the drug. There were about another 150 patients treated with oral vorolanib during those studies, and again, none, no ocular SAEs reported. There were certainly systemic SAEs from the oral treatment.
This is the reduction in treatment burden figures, about 85% in the 3 milligram and 89% in the 2 milligram, and this is historical against what they received leading into the trial. This is the same type of calculation, but this is more prospective. All the patients in the Eylea arm were to receive three injections over six months, and so we measured against those three injections, and you can see there's still about an 80% reduction in treatment burden. But notice the aflibercept arm didn't receive 3.0 injections, it was 3.3, because three eyes or 6% got rescued despite getting three injections. Also note that you can't be rescued on a day that you're getting a mandated injection. So the aflibercept eyes could only be rescued three times. The 1901 eyes could be rescued six times.
So again, quite a difference here. So this really, again, I think, speaks to the ability of our drug to keep patients stable. About two-thirds of the eyes could go up to six months without a rescue, and if you ask the question of how many received just zero or one, it's 80% of the eyes got either no rescue or just one rescue. This shows you at each visit, percentage of eyes rescue-free. Two take-home messages from this slide. The first is, it's been hypothesized by others that tyrosine kinase inhibitors are slow to work in the eye. We don't believe that's true of our drug. If it was slow to work, then you should see an excess of rescues at month three and month four, till the drug got going, and you don't see that.
The second thing is the curves are nice and smooth, which suggests that we still have drug working after six months. If the drug had run out in four months or three months, I think you'd see a sudden dip in the number of rescue-free eyes. These are the anatomic results, and remember I said that normal is up to about 280 microns. This is a generally well-controlled group going in. Remember, it's these are eyes that were previously treated, and so they were on pretty good control anatomically. And notice there was some gain in central subfield thickness in all three arms, but the difference between the Eylea and the 1901 arms was under a standard deviation of the test. Very, very small. And this shows it graphically.
At the beginning, notice all the eyes got a little bit drier because of the load. And then between month three and month four, they all gained a little bit of CST, not much. The difference here, though, is our eyes remained very stable, where we see that typical sawtooth pattern that we see from every other month Eylea. That was noted in VIEW 1, VIEW 2, and retinal specialists in general ignored it because it didn't affect the visual acuity. But what most retinal specialists want is the ability to extend in-- out the number of... lower the number of injections, extend out the intervals without sacrificing vision or anatomy, and that's what we showed in this trial. We did a subgroup analysis also, which I want to show you.
There was a question that came up: Well, perhaps, did your eyes do so well because of the supplements? The supplements raised their vision. And it turns out the opposite was true. This slide shows you all the eyes that were unsupplemented at all three groups up to month six. In the 2-milligram dose was 0.6 letters better than Eylea. The 3-milligram dose was 0.1 letter better than Eylea. So quite the contrary, the unsupplemented eyes actually did better than control. This is the OCT of the unsupplemented eyes, again, showing similar findings, very flat anatomy. Also telling you at the end, month five, month six, after our drug went in, it's not as if the drug stopped working and the eye started gaining fluid. They were perfectly stable.
To summarize, this slide shows you the results that I've gone over before, and on the right side, some of you may know that prior to the results, we had set some floors as to what we wanted to see from the results as of going forward, and we did much, much better than those floors. I want to now shift to a brief overview of our plans for phase 3, and these are plans at this point, but remember, this is all based on the Type C meeting that we had with the FDA and subsequent comments that the FDA has made two , or actually even three, I would say, big differences between DAVIO 2 in the pivotal trials. The first is the length of the study.
The pivotal trials will have a primary endpoint of approximately one year. It'll be week 52 and week 56 combined, not eight months, as we did in DAVIO 2. The second big change is we want to get a label for re-injection, and therefore, we will be re-injecting in the pivotal trials, and we plan on doing it every six months. The third difference is the number of inserts that we injected in the high dose in DAVIO 2 was three, and the low dose was two. But I think as you go through that data, you can agree that there really wasn't a dose response. And frankly, many people in the company didn't think there was gonna be a dose response, because once you're enough over the IC50 at zero-order kinetics, you've got the receptor blocked, and it's gonna stay blocked.
What that tells us, though, is there's no reason to test three inserts in the pivotal trial. We're gonna go forward with two inserts and one insert. The actual payloads have yet to be determined because we do have some flexibility around payload. We expect to start the first trial in the second half of this year. It will be U.S. and Canada. The second trial will be primarily OUS, and that should start several months later. This is an outline of the plan for that trial. It looks very similar to the outline that I just showed you for DAVIO 2, with the exceptions that I just mentioned. So the NPDR trial, called PAVIA, again, readout is coming next quarter. PAVIA enrolled 77 patients with moderate to severe non-proliferative diabetic retinopathy, and the primary endpoint in this study is not visual, it's structural.
A photograph is taken of the retina at day one, and then a photograph is taken at month nine, and a reading center independently evaluates the degree of retinopathy on a scale called the DRSS, and the standard is a two-step reduction in the DRSS. So that's what we're looking for at the nine-month visit, with secondary endpoints trying to prevent diabetic macular edema and proliferative diabetic retinopathy. So we should have that, again, results in the second quarter. However, from a safety perspective, just to update you again, of the 77 patients, probably approximately 50 got our drug, and that there had been no ocular or systemic SAEs related to the drug. We had two ocular SAEs, a hemorrhagic posterior vitreous separation, which is a common occurrence in diabetes, and an eye getting an injection, and that was eight weeks after the study eye.
And again, we don't know whether that eye received our drug or not, and we had a fellow eye get macular edema. The VERONA trial is our name of our diabetic macular edema trial, and then actually, we're proud to say we dosed the first patient yesterday. And so that trial is relatively small, planned to be 25 patients, 10 in each, a dose of EYP-1901, and a five-patient control group getting aflibercept. Everybody gets an aflibercept shot on day one, and then they either get a sham or they get our drug, and these are diabetic macular edema patients who have macular edema. So they will, a patient who's completely dry would not be in this study.
The primary endpoint is the time to first supplement, and so what we're looking for is a difference between the 1901 eyes and the aflibercept eyes for time to first supplement. And this is the supplement criteria that we're using. Starting at the first month, you can see that's actually pretty similar to what we use for wet AMD. There's one additional supplement criteria here, which is after three months, if the eyes haven't started to show anatomic improvement, we're going to supplement them also. So the last topic I want to cover is razuprotafib Durasert E or EYP-2301. For those of you who, you know, may have been following this, Aerpio was the name of the company that was developing this. They called it AKB-9778, and they were developing it in diabetes, diabetic retinopathy, diabetic macular edema, but were delivering it subcutaneously.
This is a Tie2 agonist, so it should stabilize the retinal vasculature, work well in conjunction with the anti-VEGF. They showed really terrific anatomic data, but the visual acuity data was not as good, and, therefore, they didn't continue the program. Our scientists were able to reformulate razuprotafib to put it into Durasert E, and we believe we can get therapeutic levels for six months or longer with a single injection. Our balance sheet looks great. Equity financing successful about a month ago, and again, we have about $330 million right now in cash and investments, which will take us through multiple key data inflection points and should take us through top-line results of both wet and pivotal trials. One of the things that I'm really proud of in this company is, is we've really executed well.
The first patient ever dosed with our drug, EYP-1901, was dosed in January 2021, and we have robust top-line phase 2 data in December 2023. You can see all the green checks. There are things we said we were going to do, and we did. We have a few more boxes to check in 2024, as you can see, but I'm optimistic that the team will check the boxes. Thank you very much, and happy to entertain any questions. I'm just also would like to introduce our CFO and EVP, George Elston, who's right next to me.
Thanks again, Jay, for such a wonderful presentation, and we just want to thank this, you know, take this time to thank the broader EyePoint team here sitting with us, Nancy, George, Michael, and Erin, just for your commitment in innovative and sustainable ophthalmology. So thank you so much. Now, moving on to Q&A. Please be reminded, for those of you online, you can feel free to submit those. I can read them off to you, and then for those of you in the audience, please feel free to raise your hand.
Was it that good?
Compelling.
Very good, but I'll kick it off with just one question from my side. Again, I think the DAVIO 2 results were definitely, you know, phenomenal. I think we can all universally agree on that. As you get ready for the next sort of, you know, phase of development, 2024 seems like a very, you know, catalyst-rich year, as well as 2025. Are you thinking about sort of, in terms of BD, are you thinking about sort of partnership in any way as you gear up for a commercialization in the future? If so, is it regional, or is it sort of more of a platform play, and what is your selection criteria in choosing the right partner for EyePoint?
Terrific questions, and I can say, our strategy around that has changed markedly since the data in the fundraise. I think if you'd asked the question a few months ago, I think my answer would have been, given the macroeconomic environment and given the uncertainty around our data, we probably would seek a partnership for ex-US, both clinical and commercial, to help fund the studies. We don't need that anymore. We can fund the studies ourselves, so that at this point, we're not really seeking a clinical partnership. However, we're a small company, and while I am quite confident in the company's ability to commercialize and market this drug successfully in the United States, we were a commercial company only seven months ago, and much of that commercial team is still with us.
The idea of commercializing the Anti-VEGF globally, ex US, is daunting, and I think, at some point, when the time is right, we would seek a global strategic partner to help us with the commercialization of EYP-1901.
Thank you so much, Jay. Maybe one more question on, perhaps sort of in-house manufacturing and so on.
Yep.
What is your plan for that?
So, again, excellent question. So, we manufacture EYP-1901 ourselves. There's quite a bit of technological know-how that goes into this, and we do that right now at our headquarters in Watertown, Massachusetts. We have the capacity at Watertown to make EYP-1901 for the first two pivotal trials and probably even the pivotals beyond that. However, we recognize that capacity is going to be limited... and as a result, we initiated the start of a manufacturing facility. Almost two years ago, that process started. So, we have a manufacturing facility under construction about 45 minutes west of our headquarters in Northbridge, Massachusetts.
It's a 40,000-sq-ft facility, and when it's online, it should satisfy all the commercial, EYP-1901 needs, along with we're still a supplier, for YUTIQ, for our partner Alimera here in the United States, and our partner Ocumension in China, and that would be easy to take care of that as well. The building is up. It's almost completely enclosed. We probably have six more months of construction, and then, of course, we need it to get, cleared and approved by the FDA. But we are on target and under budget with that facility, and we are confident that we'll be able to handle the commercial needs there.
One more thing that I'd like to, you know, point out and tip my hat to George, is I have to—I gotta wear a lot of hats, and I gotta keep tipping them to George. He's done such a great job. But we have a really, really good lease. We don't pay rent until four months after we take occupancy. Our landlords wanted to really try to build a biotech hub in Northbridge, and we're the first tenants, and so we got a terrific deal. All costs are, they're paying for upfront, but it's to our complete specifications.
Thanks again, George. Thanks again, Jay. One last question for George. I think we touched on a little bit about the strength of your balance sheet as you get ready for, again, catalyst-rich 2024 and 2025. Can you just elaborate a little bit more on where your balance sheet stands and how you're funded?
Yeah, so we updated this morning in an 8-K that we have $330 million of cash and investments at 12/31. Very happy with our balance sheet. We paid all of our debt off last year. Our cash guidance is through top-line data in both of the wet AMD phase III trials, which is into 2026, and it also includes covering all of our ongoing phase IIs as well. So we're very well capitalized through these key catalysts.
Perfect. Thank you. I think we have one question from the floor.
Could you speak to the PAVIA study? How much of that is de-risked from the recent wet AMD results, and what do we still need to learn in that indication?
Yeah, that's a great question. If you all heard, it was about the PAVIA study. So, every anti-VEGF that's worked in one indication has worked in all the indications. So the fact that we not only showed that EYP-1901 worked in wet AMD, but worked really well, we do think there's likely to be read-through for NPDR. The other things to note about NPDR is the shorter-acting biologics that are approved, Lucentis and Eylea. If you space out the injections too far, you lose the effect. So it's clear that constant or near-constant suppression of VEGF leads to probably better results in that disease, and therefore, a sustained-release system like ours should yield good results.
From a safety perspective, this is the first trial that we used EYP-1901 in diabetics, younger population, you know, potentially with other comorbidities, and so far, again, there's been no sign of any significant safety issue. So, we remain optimistic in the results there, and if we get results that are favorable, we would expect to initiate two pivotal trials in non-proliferative diabetic retinopathy soon afterwards.
Thank you. I have a question on just, how you're thinking about HD Eylea and Vabysmo and how that changes, and what effect it has.
It's a great question about the newer drugs that are biologics and seemingly do last a little bit longer. So first of all, remember, we're maintenance therapy, and so we're always unless we get a label for naive, we would be it would be treated with in conjunction with like and blockers. So I would say in general, it's getting very confusing for retina specialists out there. We've got regular Eylea, we got Eylea HD, we got Lucentis, we've got Vabysmo, we've got brolucizumab, which is not used much in the United States. We've got Avastin off-label, and now we have a bunch of biosimilars and a lot more coming. And the payers are starting to tell us more and more of what drug we can use.
I think in general, our view is we're agnostic to them in that the message to, to retina specialists is: get your patients as dry as you can, as stable as you can with any of them, and hand them over to us, and if our results hold, we'll be able to take 2/3 of the wet AMD population out, six months or longer with just our drug alone. For us, though, a supplement is not a failure. Supplements are fine. Doctors don't care what they inject. They just want to be able to control the pace of injections better. They may want to inject every three months, every four months, but they want to be able to do it safely and effectively without putting risk to their patients.
So again, when you think of an idea of, you know, what happens if in the real world, if you get a little fluid, you need to supplement? Well, if you kind of, again, extrapolate and do the math, in the 2-milligram arm for the six months after 1901 went in, there was 0.55 supplements. So let's say that holds into the real world. That'll be 1.1 supplements for 12 months, + 2 of our drugs. That's three injections over 12 months to 100% of the wet AMD population. I think no, no other drug is going to be able to match that. High-dose Eylea and Vabysmo in general, again, I can speak with, I wouldn't say authority, 'cause I'm not that busy anymore, but I still do see patients. I still do use those drugs.
They're giving us, in many patients, a little more longevity, but you're not going to jump a patient from every four weeks to every five weeks, every six weeks to four months. The biology doesn't work that way. We can do that, and we did it in both the phase 1 and the phase 2. So that even if you believe that our only benefit is longevity, there's still gonna be a lot of patients out there who are gonna welcome the opportunity to come in fewer times. From four times a year to three times a year is still very good for patients. So again, it's great to see advances in the field, always, but from our perspective, it really doesn't change our value at all.
Great, thank you. Curious your thoughts on the Susvimo safety issues and how that has impacted your views on just the market opportunity for port delivery.
Sus- Susvimo?
Yes.
The refillable port?
Yeah.
So, port delivery, again, I take a step back, big picture. Obviously, there's some really smart people trying to make these biologics last longer, and the best that they've come up with is a surgical procedure that puts a, you know, piece of plastic across someone's sclera. The problems that people encountered is, as I think you know, it's off the market now, not only endophthalmitis in about 1.5% of patients, but dislocation of the device and problems with the membrane. So it, it's a—for us, it was a almost a proof of concept that sustained release works. That is a true sustained release device, and they also got it FDA approved.
And so I think you can look at their phase three trial and look at the structure of it and say, "This is a pathway forward," and we've certainly done that. From a commercial perspective, before it went off the market, I don't think it was, I would say, selling a lot of them. The company, I understand, is gonna bring it back. I think that doctors and patients would probably feel better about having an intraoffice, biodegradable option, because, of course, if you don't like our, our drug, eventually it's gonna go away. If you don't like a port, it's in your eye for forever, and therefore, there's always that underlying risk that you might get endophthalmitis from that foreign body.
So again, I think that the idea of sustained release. This is, you know, the first one that got approved, but I think that we have some advantages.
Thanks, again, everyone. Thanks again, Jay and George, for a wonderful presentation and Q&A session, and thanks for everyone for joining us today. This now concludes the session.