Good morning, everyone. Thank you for joining H.C. Wainwright's fourth annual Ophthalmology Virtual Conference. My name is Max Maher, and I'm an analyst here on the corporate access team. H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to both public and private companies across multiple sectors and regions. We have a total of 24 senior publishing analysts and over 640 companies covered across all sectors. Please visit hcwco.com for more information. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. Please join us for panels that will be available live in streaming on Thursday, August fifteenth.
With that said, have a productive and enjoyable day, and I would like to introduce our presenter, Jay Duker, President and CEO of EyePoint Pharmaceuticals.
Thank you, Max, and thanks really to the entire H.C. Wainwright team for inviting me to speak today. I will be making some forward-looking statements, and for those of you who want more details, please visit our website. EyePoint Pharmaceuticals is a clinical stage company that's dedicated to improving the lives of patients suffering from serious retinal diseases. Our lead asset is called DURAVYU, which is vorolanib intravitreal insert. It's currently about to start phase III trials in wet age-related macular degeneration. DURAVYU, as well as our pipeline, represent potential multi-billion dollar market opportunities, and we deliver drugs via proprietary, proven technology that's called Durasert. In the case of DURAVYU, we call it Durasert E for erodible. EyePoint has a strong balance sheet. We've got $280 million of cash and investments as of June thirtieth, 2024. This slide represents our pipeline.
DURAVYU is currently in two active programs: wet age-related macular degeneration, for which we showed statistical non-inferiority to standard of care in a phase II trial. We're also in diabetic macular edema or DME. That trial is fully enrolled, and we expect top-line data in the diabetic macular edema trial in Q1 of 2025. Also in our pipeline is EYP-2301, which is the small molecule razuprotafib, which is a Tie2 agonist. We've been able to reformulate razuprotafib from its former subcutaneous delivery to sustained-release intravitreal delivery in Durasert E, and we're currently working on preclinical tox and PK data. In addition, in the pipeline, we are working on potential complement inhibition via sustained release, also using Durasert E technology. So Durasert E is a sustained release formulation that is completely bio-erodible.
It's performed in the retina specialist's office via a standard in-office intravitreal procedure. The inserts then provide continuous daily therapeutic dosing via what's called zero-order kinetics, which means essentially a microdose is released every minute of every day, every week, every month, until the insert is out of medication, which in the case of DURAVYU, at least in animals and in the laboratory, is approximately nine months. The DURAVYU is designed so that the drug load is depleted prior to full matrix erosion. And so in humans, we believe that the drug load should be delivered over nine months or less, with the bio-erodible matrix representing less than 10% of the volume and the weight of the insert, going away several months later. Vorolanib is a small molecule tyrosine kinase inhibitor.
It is a highly selective pan-VEGF receptor inhibitor, and this brings a new mechanism of action to VEGF-mediated diseases. Instead of blocking the ligand, we are blocking at the receptor level, and we block all isoforms of the receptor, which means we should be blocking all isoforms of VEGF. In addition, we block PDGF, which could potentially mean less fibrosis in wet AMD. In doses that we're using in humans, there's no therapeutic blockage of Tie2, no inhibition of that receptor, and that's important because Tie2 blockage would lead to upregulation of angiopoietin-2, which would destabilize retinal blood vessels. In a preclinical model, we showed that vorolanib may be neuroprotective, and that has been now published. And of course, I already mentioned the potential anti-fibrotic aspect of blocking the PDGF receptor. This slide shows an image of DURAVYU insert.
They're cylindrical, they're solid, they're heavier than water. After injection, they sink to the bottom of the vitreous cavity and generally stay there. Our drug, vorolanib, is immediately bioavailable. In fact, because of some excess vorolanib on the surface of the inserts, within the first few weeks, we get very high doses of the drug, which, several weeks later, go into that zero-order kinetics, which I mentioned. We believe in humans, we will be able to get therapeutic levels for six months or longer, and again, the drug should be fully depleted by nine months. One important aspect of DURAVYU is it can be shipped and stored at ambient temperatures. It does not require refrigeration or freezing. We've performed four clinical trials with DURAVYU, and they're listed here on the left. DAVIO was the phase I wet AMD trial.
DAVIO 2 was the Phase II wet AMD trial. The PAVIA trial was an NPDR trial that we read the top line out from earlier this summer, and the VERONA trial is the DME trial that I mentioned already. We've now treated a total of 191 patients with DURAVYU, with good follow-up and very favorable safety profile. We've seen no DURAVYU-related ocular or systemic SAEs. I'm gonna go over now the results of the Phase 2 DAVIO trial in wet AMD. This was a multicenter randomized trial of previously treated wet AMD patients. We enrolled 160 patients, and the patients were randomized to one of three arms. The high dose of DURAVYU was 3 inserts or 3 milligrams.
Approximately, the lower dose was 2 inserts or 2 milligrams, and by the way, those multiple inserts are all delivered with a single injection through our sterile injection system. The control group was on-label aflibercept. All patients in this study needed to get an anti-VEGF injection 2 weeks, 5 weeks prior to screening, and then once they were randomized, at day one, week 4, week 8, all patients received an aflibercept injection. At week 8, thirty minutes after the aflibercept, they either received a DURAVYU or they received a sham if they were randomized to the aflibercept group. Patients were then seen monthly, and they were evaluated for disease activity on a monthly basis. Every other month, the aflibercept arm received another aflibercept on-label. The DURAVYU arm received a sham for masking.
All three arms could be subjected to supplemental injections if they met the criteria for disease activity. The primary endpoint in this study was non-inferior change in visual acuity, and this was measured as a blended endpoint between week 28 and week 32. This is the baseline characteristics of the patients enrolled in the trial, and as you read across, you can see they're well-balanced. Two things to note: First of all, the mean CSTs were essentially normal. Up to 280 microns is a normal fovea. The reason they were normal in this case was, what I mentioned already, is that all patients had to receive an anti-VEGF 2 weeks to 5 weeks prior to screening.
The red circle shows the number of injections normalized over the prior year that these patients received, and on average, it was close to 10 injections in all three groups. This shows you that this was a heavily pre-treated group, a group of patients that needed a lot of anti-VEGF therapy to maintain their vision and their anatomy. This slide shows the top-line result of best-corrected change in visual acuity compared to the aflibercept control. And in fact, in the blended endpoint, you can see the 2-milligram arm had less than half a letter difference than the Eylea arm, as did the 3-milligram arm. And this was highly statistically significant, not only to 97.5% confidence interval in non-inferiority testing, but a p-value for difference of 0.0009 or less for both groups.
This slide represents the reduction in treatment burden that the 2-milligram and 3-milligram arm showed over the prior year. Meaning the patients, this is retrospectively, the patients received approximately, on average, 5 injections over the prior 6 months leading into this study. For the 6 months after they received DURAVYU, you can see they, in the low-dose arm, it was 0.55 injections of supplement, and the high-dose arm was 0.73. That represents the numerator, the mean number of injections over 6 months. The denominator gives you an over 80% reduction in treatment burden over history. We also calculated reduction in treatment burden prospectively. Remember, all the patients in the aflibercept arm mandated to receive 3 injections after week 12.
You can see they in fact received on average of 3.28 injections because there were rescues in the aflibercept arm. And when you do the prospective reduction in treatment burden, you still get numbers right around 80%. This slide represents the percentage of eyes that were rescue-free up to each visit. And notice, that at month 8, which is six months after DuraVu went in, about two-thirds of the eyes were rescue-free. In comparison, actually, despite getting 3 Eylea injections over from between month 4 and month 8, the 6% of the control arm, the Eylea arm, still needed supplement. Again, showing evidence that this was a group of patients that required a lot of treatment. This is the swim lane for 2 milligrams, and this shows some interesting things.
You obviously can see on the left, those black dots represent the number of injections that the eye got prior to enrollment, and then on the right, the red dots are the number of injections that the patients got after they received DURAVYU. And you can see it's quite a bit of reduction. Some interesting things, if you even look at the bottom patient, which is patient 53 on the right, you'll see that this patient got 3 supplements. And you might say, "3 supplements, that's quite a, quite a number of supplements." When you go back and look how many injections that patient got leading into the trial, that still represents a significant reduction in treatment burden. The next slide, this is the same swim lane plot, but this is for the 3-milligram arm, showing similar results.
About two-thirds of the patients received no supplement up to month six, and even patients that required supplement appeared to do so in general at a much reduced rate of what they were getting leading into the trial. This is the anatomy of the patients. This is, again, represented by OCT, which measures retinal thickness. I mentioned already 280 microns approximately is normal. About 10 microns is the standard deviation of the test. Anything over 300 microns is considered to be thick. And when an eye has high VEGF levels, the macula becomes thicker. A couple things to note.
First of all, for the first 3 months, all 3 arms had a slight reduction in the thickness of their maculas, suggesting that even though eyes were heavily pre-treated and received an injection 2 weeks to 5 weeks before the trial, some were still undertreated and got a little better anatomy from the load. Between month 3 and month 4, all 3 arms did show a little bit more fluid, but not a lot, and then after that, the DURAVYU arm stabilized. If you look at the green line, however, that's the Eylea arm. Notice how it's sawtoothing. That sawtoothing pattern tells us something very important, that we enrolled a group of eyes that absolutely needed treatment. If this were a group of eyes that didn't require treatment, you would expect that the Eylea arm OCTs would be generally flat.
The other thing that this shows with the sawtoothing is if you superimpose that sawtoothing on VIEW 1, VIEW 2 after the load, which are those are the two pivotal trials that got Eylea approved, you can see that the sawtooth pattern is almost identical. That suggests that we enrolled a patient population that was very similar to the patient population in VIEW 1, VIEW 2. The difference at the end between the arms, you can see 12 microns from DURAVYU 2 milligrams, and only 5 microns from DURAVYU 3 milligrams, which is minimal. This slide represents the primary endpoint at the top, non-inferior change in visual acuity, which I mentioned already, and you can see all the secondary endpoints were also hit, including, and most importantly, safety.
We did some subgroup analyses of DAVIO 2, and I'd like to highlight one of them. This is the subgroup of patients that were not supplemented. So about two-thirds of the DURAVYU arm were non-supplemented. 94% of the Eylea arm is non-supplemented. And this is the visual acuity results, and notice that the non-supplemented eyes in DURAVYU actually numerically did better visually than the Eylea patients did. So this slide shows you that this unsupplemented eyes did very well, and the use of supplementation did not drive the results. This is the anatomy of the unsupplemented eyes. And again, what you see is the sawtooth pattern in Eylea, showing you that this was a group of patients that absolutely needed treatment. But again, notice how flat the anatomy was after month 4 in the DURAVYU arms.
In fact, if you look at month 8, there's virtually no difference in the anatomy between the unsupplemented eyes that were treated after month 12 with nothing else other than DURAVYU, and the supplemented eye or the eyes in the control group, which received every other month Eylea. Just recently, we reported the 12-month top-line results from this trial, and again, the trends that we saw at 8 months continue with some excellent results. This is the change in visual acuity at month 12. At DURAVYU 3 milligrams, the higher dose showed absolutely no difference between the visual acuity change in Eylea, whereas the DURAVYU 2 milligram was again under a half a letter difference. Again, highly statistically significant. In the anatomy at month 12, the sawtooth pattern of the Eylea arm didn't change.
These eyes continued to need anti-VEGF, but you can see, nice, continued flat of the curves in the DURAVYU arms. At month 12, if you look at the high dose, they... it was right on par with Eylea. Once again, we had no DURAVYU-related ocular or systemic SAEs in this trial, with no signs of the insert migrating into the anterior chamber. Of that 191 patients that I mentioned that we treated, we've seen no evidence of insert migration. We've seen no evidence of retinal occlusive vasculitis, and there was a very low patient discontinuation rate in this trial. At month 8, the discontinuation rate was 4%, and none of the discontinuations were related to DURAVYU treatment.
So the top-line summary, after a single injection of DURAVYU, eyes were able to maintain stable visual acuity and excellent anatomic control, and at month 12, about half of the DURAVYU eyes were supplement-free. Interestingly, at month 12, approximately 22% of the Eylea eyes received the supplement. So, once again, more evidence that suggests that this group of patients that we enrolled was a highly anti-VEGF needy group. So I'd like to now discuss our phase 3 pivotal trial design. We have two nearly identical pivotal trials planned. The objective is to show that DURAVYU, when administered every 6 months, would give similar visual acuity outcomes to on-label aflibercept while reducing the treatment burden. We're gonna enroll approximately 400 patients in each of these two trials.
In each trial, we'll have two arms, one dose of DURAVYU at 2.7 milligrams versus the on-label aflibercept control. The primary endpoint is change in best-corrected visual acuity blended, but, unlike DAVIO 2, where the endpoint was at week 28, 32, the endpoint in the pivotal trials will be a combination of weeks 52 and 56. The significant secondary endpoints are safety, reduction in treatment burden, and the percentage of eyes that remain supplement-free and anatomic stability. Some of the key trial design elements about our trials, and they were designed to drive global regulatory and commercial success. At present, we are the only sustained release wet AMD program under study that's evaluating reinjection for the label, and we think that's an important distinction.
Being able to redose as soon as every six months with sustained release, I think will give patients and physicians flexibility. We're planning on enrolling patients with active wet AMD, both previously treated and treatment naive. And remember, even the treatment-naive patients, by the time they get DURAVYU, will not be treatment naive because they'll have received three loading doses of Eylea. Sham injections will be used for masking, and the primary efficacy endpoint will be again at 12 months, and that's the basis for the NDA submission. We will monitor all the patients for an additional year, and so we'll have safety data over two years. At present, we are on track to be the first sustained release wet AMD program under study that is planned two pivotal trials to enable NDA submission to the FDA.
This is an outline of the trial, and this looks very similar to what I've showed already with DURAVYU. Differences again, primary endpoint is at approximately one year, and we're reinjecting every six months. The broad patient population, both previously treated and naive, has the potential to really enhance the trial outcome, and we also believe it will increase commercial opportunity. We think enrolling a broad spectrum of wet AMD population that's seen in the naive eyes will increase the number of supplement-free eyes. It will also give us a broader label with global reimbursement, and we think so enrollment will be speedy. We have, at present, actually over 100 sites selected to be in the first trial.
All patients, again, will receive the three loading doses, so even though they may have not received any treatment prior to enrollment, they will prior to receiving DURAVYU. This again broadens our commercial opportunity, we believe, by broadening the type of patient that we're enrolling. Remember that we enrolled a very tough-to-treat population in DAVIO 2, but the patients who what we refer to as pseudo-naive, meaning they had been only diagnosed three months prior to enrollment in DAVIO 2 and had received two injections, they had a supplementation rate that was lower than the average patient in DAVIO 2. So we think that those pseudo-naive patients speak well for the ability for the naive patients to maintain vision without supplementation. I want to talk briefly now about the VERONA trial, which is Diabetic Macular Edema trial.
This trial is now fully enrolled with 27 patients, top-line data in Q1 of 2025. These are all previously treated DME patients with active DME. They had to have abnormal OCTs. The primary endpoint here is time to first rescue. We will be measuring visual acuity, supplement-free rate, et cetera, as well as safety, but different endpoint than what we looked at in the wet AMD phase II. This is the supplementation criteria for VERONA. The top four are the same as what we used in DAVIO 2 for wet AMD, but we added an additional one, which is at week 12, if the CST has not gone down, then supplementation should be given. And finally, a word about razuprotafib in Durasert E, which is EYP-2301. Razuprotafib is a Tie2 agonist.
This is a new molecular entity that we have patented, and we will be testing this in serious retinal diseases, most likely as supplementation to standard anti-VEGF to try to get superiority of visual acuity. By agonizing Tie2, you downregulate Angiopoietin-2 and upregulate Angiopoietin-1, which does give increased vascular stability in the retina. This slide shows you some upcoming presentations. This month, we have American Retina Forum. We're presenting at Retina Society in Portugal in September, and the EURETINA meeting, which is in Barcelona, also in September. We're doing further subgroup analyses for the 12-month data at the Pre-Academy Subspecialty Day in AAO, and we have an encore DAVIO 2 presentation at FLOREtina. And I'd also like to point to 2 recent publications concerning EYP-1901.
We have published the phase I trial now, as well as some good background on vorolanib as compared to other TKIs that are under study. Thank you very much for your attention.
Jay, I just want to thank you so much, you and the whole team from EyePoint Pharmaceuticals, obviously for leading a great and productive presentation today. Obviously, all of us here at H.C. Wainwright are recognizing how much work goes into putting together a corporate deck like this. So thank you from everyone here at H.C. Wainwright.
It was my pleasure, Max. Thanks for having me.
Of course.