Good afternoon. Thanks for listening. My name is Jay Duker. I'm the President and CEO of EyePoint. I'd like to thank Goldman Sachs for inviting us to present today. We are a publicly traded company, and I will be giving some forward-looking statements. If you'd like our full legal disclaimers, I invite you to go to our website. EyePoint is the leader in sustained-release drug delivery for retinal diseases. Our lead asset is called DURAVYU, which consists of Vorolanib, a small molecule tyrosine kinase receptor inhibitor, which is best in class. It's patent protected. It's in our patented Durasert E sustained delivery technology, which makes the inserts fully bioerodible. We are currently in two pivotal phase III trials in wet age-related macular degeneration. The first trial is called the LUGANO Trial, and we announced several weeks ago that the trial is now fully enrolled with over 400 patients randomized.
The second trial is called the LUCIA Trial. We announced it's 60% enrolled as of several weeks ago, and we've updated our guidance to have full enrollment in the LUCIA Trial in the third quarter of this year. In addition, we're the only TKI program to be in diabetic macular edema, or DME. We had highly positive efficacy and safety data from our phase II VERONA trial in DME. In fact, we've had favorable safety profile across multiple indications with over 190 patients treated with DURAVYU to date. Our cash looks great. We currently have $318 million at the end of the first quarter, which gives us a runway into 2027, approximately a year post data from the phase III trials. This is our pipeline. Again, we are in phase III in two wet AMD trials, LUGANO fully enrolled, LUCIA by 3Q.
We have positive phase II DME data, and we will be updating our DME plan later in the year for pivotal trial. In addition, we have EYP-2301, which is the small molecule called razuprotafib that we've been able to put into sustained release. This is a type two agonist, and we will be advancing it for serious retinal diseases. We have some pretty good treatments for wet age-related macular degeneration. They're safe and effective, but they all lack one thing, which is durability. There is significant evidence that we need more durability in wet AMD. Many patients are chronically undertreated, and in the long term, many patients lose vision because they are undertreated. The short-acting current anti-VEGFs put a great burden on patients, on practitioners, on families, and on society. Missed visits can result in permanent visual loss.
There's evidence that even one missed visit in scheduled therapy could result in significant visual loss. The fact that we have an aging population with increased lifespan only means there's going to be more and more patients who get wet age-related macular degeneration and require long-term therapy. Diabetic macular edema is another area for which we have good treatments, anti-VEGFs that are safe and effective. Durability is needed. Diabetic macular edema typically affects working-age people who have multiple concurrent clinical problems, have to go to multiple doctor visits. The significant burden of intravitreal injections, especially in the first year, means that patients can be very non-compliant in this disease. DME is prevalent. About a quarter of the patients will develop it. Currently, the market is about $3 billion. Up to 51% have delayed or missed visits resulting in significant visual loss. Our solution is DURAVYU.
DURAVYU, again, is a small molecule tyrosine kinase inhibitor that is in our patented delivery system that we call Durasert E, E for erodible. The Durasert delivery system has already been in four FDA-approved products in a non-erodible form. Durasert E is, each insert is tiny. It's about one five-thousandth of the vitreous cavity. It's delivered in the retina specialist's office with a standard intravitreal injection. Durasert E provides continuous dosing, what we refer to as zero-order kinetics. Zero-order kinetics means after initial burst of the drug, you get a steady state release for the lifetime of the insert. In humans, we believe the inserts will last a minimum of six months in all patients. The majority of patients should have the drug depleted by month nine. These are solid injectable inserts.
They're in a biorotable matrix, and they are designed to release the drug fully before the matrix goes away. What you don't want is your matrix to go away before the drug is fully eluted because you will then have free drug particles in the eye, which can be a problem. We have a favorable safety profile across multiple indications. Again, this is a fully erodible matrix. Vorolanib is a small molecule tyrosine kinase inhibitor. It selectively inhibits all VEGF signaling because it inhibits all VEGF receptors. In addition, it inhibits PDGF, which should lead to an inhibition of fibrosis. In the long term, there are three reasons why wet AMD patients lose vision. The first is non-compliance. The second is fibrosis. Our drug should tackle both of those problems. Durasert E, again, one five-thousandth of the vitreous cavity for each insert.
Our scientists have been able to manufacture this in a way that it is now 94% drug, only 6% matrix. We have shown in animals and now in humans, looking at our diabetic macular edema data, that we have no delay in the onset of our drug release. In animals, we've shown the drug reaches the choroid within hours and within a day is at therapeutic levels. The zero-order kinetics results in no fluctuations, which should mean no fluctuations in control of the fluid, which is important for long-term visual acuity. We have no free-floating drug particles in the eye. Interestingly, we don't need cold storage. We can be shipped and stored at room temperature, which is a real advantage when you think about how big the freezers that retina specialists have to have with all the current FDA-approved products. Also, very important, we have no PEG.
PEG has been implicated as the cause of potential vasculitis in sensitive patients. We do not have any PLGA. PLGA releases into an acidic environment and has the potential to cause corneal toxicity. We have completed four studies so far: the DAVIO phase I wet AMD trial, the DAVIO two phase II wet AMD trial, PAVIA NPDR trial, and VERONA phase II DME trial. A total of 191 patients treated with our drug with no safety concerns. We have had no DURAVYU-related ocular or systemic SAEs reported to date. There has been good to excellent efficacy shown through these four trials. I am now going to talk a little bit about our exciting wet AMD program, the LUGANO and LUCIA trials. These trials are designed as a non-inferiority primary endpoint. This is an established approval FDA pathway. The last four wet AMD approvals have been with a non-inferiority design.
We had a non-inferiority robust phase II trial, which showed excellent results. Our phase III program was modeled after that. We have had proactive FDA interaction, both at a type C meeting in 2022 about our pivotal program and again at an end of phase II meeting in April of 2024, with agreement with the FDA on the trial design and written alignment on our masking and our non-inferiority margin of - 4.5 letters. This is also what we refer to as a real trial design. Doctors are used to the on-label 2 mg EYLEA control arm. They know how it is going to behave. A drug against it, they will know how to use this in the real world. To review the DAVIO two phase II wet AMD results, we had two doses of our drug, 2 mg and 3 mg versus an on-label EYLEA 2 mg control.
There was essentially no change in visual acuity at the primary endpoint. The 2 milligram arm was - 0.3 letters worse than EYLEA. The 3 milligram arm was - 0.4 letters worse. When you did this as a p-value, the p-value for these being identical to control was 0.0009. We had essentially the same control of vision that on-label EYLEA had. I've emphasized safety already, but the reduction in treatment burden was about 80%, depending on how you measured it. Reduction in treatment burden can refer to a retrospective look back on how many injections did these patients receive leading into the trial. We had about a 90% reduction in treatment burden looking at it this way versus how many shots within the trial did the patients get after the load. We had about an 80% reduction looking at it that way.
This was a tough-to-treat group in our phase II. They were previously treated patients who, on average, had about 10 injections a year normalized leading into the trial. In the United States, on average, patients receive about six injections a year. This truly was a needy VEGF-mediated disease patient population. Two-thirds of the eyes made it about six months after our drug was inserted without any supplement, and about 50% made it a full year. We had excellent anatomic control. Anatomy is measured on optical coherence tomography, or OCT, with a normal foveal thickness of about 300 microns. Anything above 325 is considered to be abnormally thick. You can see from this slide that the anatomic control was less than one standard deviation of the test. This went on to inform our phase III trial design, which you can see on this slide.
The phase III trial design consists of two arms: DURAVYU 2.7 mg, which is our higher payload insert with 94% drug payload, against on-label aflibercept control. All patients get randomized on day one. They receive aflibercept at day one, week four, week eight. 30 minutes later, they either receive their first dose of DURAVYU or they receive a sham. Patients come in monthly and are evaluated monthly. Every other month, the DURAVYU arm gets a sham. The aflibercept arm gets another aflibercept. At week 32, a second injection of DURAVYU is given. We are hoping for a label of every six months. This is a two-year trial, but we expect to submit the NDA at the end of one year. Again, the primary endpoint is non-inferiority change in visual acuity between the DURAVYU arm and the control arm with a blend of week 52 and week 56.
LUGANO is fully enrolled. LUCIA should be fully enrolled in 3Q of this year. A couple of announcements to make about this as well. We're really proud to announce that the EMA has approved our protocol. So we now have approval of the two largest regulatory agencies in the world. Some of you may be aware that the EMA barrier to approval for clinical trials is somewhat higher than the FDA. That also leads us to be optimistic that should our trials prove to be positive, we could get approval in Europe. We have now the first European site in the Czech Republic up and running and have now enrolled the first OUS patients in the LUCIA trial. This is a timeline for the trials. Again, starting in January of this year, and you can see how rapidly we were able to enroll LUGANO.
Again, we were enrolled over 400 patients in about seven months. It is, we believe, the fastest enrolling wet AMD trial recorded to date. LUCIA started several months behind but is enrolling at approximately the same rate. We expect top-line LUGANO data in mid-2026, top-line LUCIA data several months later. They are identical trials. If we have a positive top-line in safety at LUGANO, we have every reason to believe LUCIA will have a similar result. I'd now like to talk a little bit about diabetic macular edema. DME is also a prevalent problem worldwide. We did a phase II VERONA trial in DME. The attempt here, of course, is to reduce the treatment and visit burden in diabetics without harming the visual acuity outcome.
You can see from this slide with the four approved products how often the patients need to come in for injections. At the bottom, what we hope to accomplish with DURAVYU with every six-month dosing. The VERONA trial enrolled only active DME patients. They had to have decreased vision, and they had to have significant fluid to be enrolled in the trial. This is the first trial which we enrolled patients that 100% had wet maculas. On day one, the patients received aflibercept. Then 30 minutes later, they either received 1.3 mg of DURAVYU or 2.7 mg of DURAVYU, or they received a sham. The primary outcome of this study was not visual acuity. The primary outcome was time to first rescue. There were no other mandated injections in this trial after day one.
The patients came in monthly, and they could be subjected to supplemental injections if they met supplemental criteria. This is the top-line result of the VERONA trial. The high dose, the 2.7 mg dose, which is the dose we're using in the phase III and our presumed go-to-market dose, showed that the primary endpoint was achieved, extended time to first supplement versus the aflibercept control. We had early improvement in both best-corrected visual acuity and anatomy measured by central subfield thickness on OCT, with the improvement of seven letters at the end of the trial and - 76 microns drier in CST. Again, safety looked very good. No SAEs reported due to the drug. This is the curve of visual acuity. I'm only showing the first part of the curve here because no patients received the supplement before week 12.
This is directly head-to-head EYLEA versus DURAVYU. You can see at week 12, the blue line, which is the high-dose DURAVYU 2.7 mg, was significantly better than EYLEA. I also like to point out week four. Week four is directly head-to-head DURAVYU against a single EYLEA in a wet population. Look at the improvement in visual acuity and drying that occurred as early as week four. This was sustained for most patients throughout the study. If you're a patient and you have decreased vision and a wet macula due to DME, would you rather get better at four weeks? Would you rather get better in six months? I think most of us would pick four weeks. This is an early and sustained effect in visual acuity through the length of the study.
At the end of the study, all three arms ended up with the same visual acuity, which is fine because in the pivotal trial, we'll likely do a non-inferiority. We don't have to be better than EYLEA. We just can't be significantly worse. Within this trial, however, there was a single outlier. If you go back and look at the blue line again and look between week 20 and week 24, notice how the visual acuity drops. That drop was a single patient who lost 20 letters. They were late coming in. That week 24 visit should have been a week 20 visit. By the way, they did get supplemented at week 24, and their vision came back.
If you take that patient out of the equation and just look at the rest of the patients in the high dose, the high dose gained 10 letters, significantly better than EYLEA. This is the anatomy. Once again, what's powerful about this is the anatomy and the acuity, the structure and the function match perfectly. The visual acuity improved in four weeks, and the anatomy improved in four weeks. That tells you it's real. This is, again, what retina specialists look for. They look for the improvement in anatomy because we know that the visual acuity can lag sometimes in this disease, especially when treating with anti-VEGFs. It can take many months for the vision to improve. With a high dose, we had early and sustained improvement in both the vision and the anatomy.
That continued in the high dose and in the low dose as well throughout the study with 75 micron improvement versus only a 43 micron improvement in the EYLEA arm. We then went on to do a subgroup analysis and said, "Let's just look at the eyes that were unsupplemented. They purely got our drug, or they purely got a shot of EYLEA. Let's see how they did." The top is the visual acuity. Again, the blue line is 2.7 mg DURAVYU only after that single shot with EYLEA day one. Notice that the improvement in vision is seven letters at week four and about 10 letters at week eight. It is very fast vision improvement. It is sustained. The line is flat through the rest of the trial. What this tells you is when this drug works in DME alone, it works really well.
These patients were not gaining fluid or losing vision at the end of the trial. Again, look, the second graph at the bottom is the CST, early improvement of 120 microns. Now, these eyes started at 420 microns. 420 - 120 is 300 microns on average. They were normal within a month after injection. It was sustained throughout the study. Again, about 70% of the patients were rescue-free in the high dose and t he results were really, really fabulous. Now, I want to show a couple of cases. This first case is from the 2.7 mg arm, and they did not get supplemented. This is purely with our drug. On the top left is the screening. You can see this eye has swelling. If you have never seen an OCT before, these black areas in here, that is the fluid within the retina.
Best-corrected visual acuity is 50 letters. That's not great. 20/20 is 85 letters. You can see between screening and day one, the eye got worse, dropped four more letters, and got more fluid. What did they receive before? They had two EYLEA injections 12 months and 10 months before enrollment. They had a Vabysmo seven months before enrollment. Vabysmo probably wore off by then. You can see this is active disease. How did they do? Take a look. At month one, that is a normal foveal contour, normal macula, and improved about 20 letters at month one and stayed improved through month six. You could argue, "Maybe that EYLEA did the job for that month one." Maybe, except that the EYLEA would have worn off by month six.
That shows that immediate improvement in good longevity of our drug in this DME patient. The next case, I think, is even more impressive. If you look at the top right here, you can see this patient got Avastin nine months before enrollment and then basically got monthly Vabysmo. If you think the retina specialist is giving monthly Vabysmo, why are they giving it monthly? Because they feel like they need to. Otherwise, they would have extended the interval here. How did they look two months out of the last Vabysmo? They had a cyst of fluid. They had 72 letters. Several weeks later, after screening, when they actually got enrolled, they had even more fluid. At month one, they had less fluid, not a lot less, still had some activity. You might say, "Okay, that was the EYLEA effect." Maybe.
At month four, there's almost no normal foveal contour. Look at the improvement of about 15 letters. That's three lines on the eye chart. Look at month six. No fluid, no normal foveal contour, 80 letters. Here is six months after our drug went in. Take a look at what they were two to three months after Vabysmo. I think you argue in this eye, our drug was better than Vabysmo for DME. The summary of VERONA is we met the primary endpoint for both doses, immediately clinically meaningful results without a full load of aflibercept, just one. We got that significant improvement, and it lasted in the high dose through the length of the study. The subgroup analysis showed that the supplement-free eyes were what was really driving the excellent result and continued favorable safety and tolerability.
We have an end-of-phase II meeting scheduled with the FDA for next month. We will update investors and analysts at likely the end of the summer, early fall, and what the plan is for DME. At present, we intend to start the DME pivotal trial or trials in 2026. We're very proud of our new manufacturing facility. Our planning all along has been to grow EyePoint as a successful pharmaceutical company, not just thinking about the next clinical trial success, but long-term success and long-term drug development. We realized several years ago that our Watertown facility was not going to be adequate for commercial. We sought out a new facility. We looked all over the United States, ended up with a site about 45 minutes west of Watertown in central Massachusetts in a small town called Northbridge.
We built a 41,000 sq ft facility with eight state-of-the-art clean rooms that opened in October. This is built to U.S. FDA and EMA standards. We actually had the FDA involved in some of the planning. We had their sign-off on the plans. We are in the midst of doing DURAVYU registration batches to support the future NDA filing. We would expect that this facility could fully support, if successful, the commercial activity for DURAVYU both in the United States and ex-U.S. We believe that we can make over 1 million inserts a year potentially in this center. This has been a really, I think, terrific story of execution by EyePoint. I do like to brag that the first patient ever treated with DURAVYU was treated in January of 2021.
Here we are about four and a half years later, fully enrolled in one pivotal trial with another one about to fully enroll, a brand new manufacturing facility, and really terrific efficacy and safety data for our drug. The green checkmarks show you some of the things we have done in the last year with upcoming events, the end-of-phase II meeting for DME, full enrollment for the LUCIA Trial we expect in 3Q, and top-line data for LUGANO mid-2026. Thank you again for the invitation. Appreciate you all listening. If there are any questions, happy to answer.