EyePoint, Inc. Common Stock Study result

Good morning, everybody. Thanks for giving us your time this morning. I am pleased to report the top line data from the first of our two wet AMD pivotal trials for DURAVYU, the vorolanib intravitreal insert. These are our legal disclaimers, and this is the agenda for today's meeting. EyePoint is a leader in sustained drug delivery for retinal disease. We are currently in two phase III programs in the two largest retinal disease markets, wet AMD and diabetic macular edema. Beyond today's discussion, we also have multiple potential catalysts over the next 16 months, including LUCIA phase III data, a potential wet AMD NDA filing, DME top line data expected in about a year. We have had excellent execution in our four phase III trials with rapid enrollment and a commercial cGMP facility in place for our U.S. launch.

DURAVYU has significant advantages, and we believe it represents a differentiated program. We have broad clinical programs, as I have already mentioned, wet AMD and DME. We show a very favorable safety profile. Our trial design is clinically relevant. One potential advantage is this multi MOA mechanistic edge that RTKI may show in clinical trials. We not only block all the VEGF receptors in PDGF, but we also block the JAK1 receptor, which gives us the ability to block the downstream effects of IL-6. Our Durasert technology has been approved in four prior FDA products. This slide shows you at the top our wet AMD program, at the bottom the DME program, and today's focus is on LUGANO, the first of two phase III wet AMD programs. This is the design of both LUGANO and LUCIA trials. In LUGANO, we enrolled 432 patients.

They were randomized to two arms, one to one, DURAVYU 2.7 milligrams or on-label aflibercept control. This is the first study that looked at repeat dosing of DURAVYU. It was given every 6 months. The primary endpoint is one-year efficacy and safety. The studies are planned to go on for 2 years for safety. The primary endpoint of both studies is non-inferiority mean change in vision from day 1 to averaged week 52, week 56 versus the aflibercept control, and the non-inferiority margin is -4.5 letters. Key secondary endpoints are listed on this slide as well. This is the schematic of the study. A couple things I would like to highlight. First of all of the eyes in the trial were loaded with monthly EYLEA. At week 8, the eyes that were randomized to DURAVYU got a DURAVYU injection about 30 minutes after their third EYLEA.

DURAVYU was then redosed every 6 months, while the EYLEA control was redosed every other month. The reduction in treatment burden calculation is performed after the EYLEA load. Note that the week 56 injections do not count. They are in the second year. Therefore, by design, the DURAVYU eyes each will receive two DURAVYUs in the first year after the load, and the EYLEA eyes should receive five EYLEAs after the load. Here are the results. First of all, baseline demographics. Nothing really to note here. As is true in most wet AMD trials, it is predominantly a female population. We enrolled both treatment naive and previously treated eyes in about a 75/25 ratio. The previously treated eyes were a heavily pretreated group with on average over seven injections a year leading into the trial.

For those of you who recall the DAVIO 2 previously treated cohort, they came in with more injections. Remember, in DAVIO 2, injections were given right up until the time of randomization. In this trial, none of the eyes could have been treated with an anti-VEGF within 8 weeks of screening. Further baseline characteristics. Best corrected visual acuity. DURAVYU eyes started about a letter and a half better, and the total CNV areas was a little bit larger in DURAVYU. The larger the CNV in general, the worse the eyes will do. But analysis so far do not suggest either of those factors played into the results. I have highlighted a couple of things in the medical history. First of all, about 25% of the DURAVYU eyes gave a history of having dry AMD going into the study, versus about 22% of the aflibercept arm.

But almost twice the number of patients in the DURAVYU arm gave a history of having glaucoma. This slide shows the top-line results. We believe that LUGANO demonstrated clinically meaningful results that reinforce its potential of DURAVYU to improve the treatment paradigm in wet AMD. When DURAVYU was studied for non-inferiority by excluding an asymmetric cohort of only nine eyes or 4%, DURAVYU was non-inferior. However, in the full data set, confounded by these nine asymmetric patients who experienced visual loss greater than 15 letters from non-wet AMD etiologies, DURAVYU was not non-inferior. When looking at the secondary endpoints, 42% reduction in treatment burden through week 56. Remember, the ceiling was 60%, and this was highly statistically superior to standard of care. About 76% of the eyes in DURAVYU were supplement-free up to week 32. That was 6 months after the first DURAVYU went in.

54% remained supplement-free through the end of the first year, meaning over half of the eyes in the DURAVYU arm were controlled exclusively by DURAVYU. Anatomic control was excellent. The CST difference at week 56 was only four microns, and we showed continued favorable safety profile. Let us look at the visual acuities first. What you are seeing on this slide is the graph of the visual acuities. The top gray being the control arm, and DURAVYU is in purple. You will see when we excluded this asymmetric cohort of nine eyes, DURAVYU was non-inferior to on-label EYLEA. So who are these asymmetric cohort? Remember, these are elderly patients, and they can lose vision for reasons other than wet age-related macular degeneration. That is to be expected. In the DURAVYU arm, however, nine patients lost greater than 15 letters of vision due to non-wet AMD etiologies.

That included 6 patients who lost significant vision from geographic atrophy, dry AMD. Two patients lost vision from glaucoma, and one lost vision following a retinal detachment. Interestingly, all 9 showed good anatomic control of their wet AMD, and 6 of these 9 eyes received a supplement at some point in the study, but none of the supplementation improved their vision. These 9 eyes accounted for a total of 258 total losses of letters. Why are we calling this asymmetric? Because in the aflibercept control group, surprisingly, none of these eyes lost more than 15 letters due to a non-wet AMD diagnosis. Looking at the graph top right, the dotted line is the DURAVYU eye's visual acuity results when the 9 asymmetric eyes are removed. Notice about 5 letter improvement that is maintained throughout the trial.

The solid purple line is the visual acuities of the 9 patients who lost vision due to non-wet AMD diagnoses. Notice they never really gained vision, and they steadily lost vision throughout the trial. When looking at their anatomy, what's surprising at first glance is that their OCTs were actually thinner than the rest of the cohort. The cohort overall showed good control of fluid. But when you think about it, geographic atrophy is atrophy, and it's no surprise that those 9 eyes actually had thinner maculas than the rest of the cohort. This was not due to active wet AMD, however. This slide shows the full data set, showing that the primary endpoint was not achieved. There was approximately 3.8 letter difference between the two groups. Recall, if the 9 eyes were removed, it dropped to a 2.4 letter difference.

The bottom graph is the CST on OCT, central subfield thickness, and notice again, at the end of the trial, there was only a 4 micron difference. So why are we calling this asymmetric? This slide shows you the number of 15 letter losers that occurred in prior studies that involved 2 mg EYLEA. And you can see looking at the right side of this chart, it hovers around 4%-5% and averages about 4%. In LUGANO, at the bottom, it was only a half a percent. So this was highly unusual in an elderly population that there weren't additional patients who lost significant vision due to non-wet AMD diagnoses. So what did our preliminary evaluation conclude about this? The first question is: Was this asymmetries in adverse events? Is that what resulted in the visual outcome result? And the answer appears to be no.

Cataracts were evenly balanced between the two arms. Intraocular pressure increase, evenly balanced. We had very little intraocular inflammation or IOI, only one patient in each group, and the IOI was not severe. These are investigator-reported percentages of dry age-related macular degeneration, and you can see, while no statistical difference, there was a trend for more dry AMD overall in the aflibercept arm. There was one patient in each arm that had a detached retina, and that percentage is typical for this type of trial. However, the eye that had the detached retina in the aflibercept arm gained a letter. The eye in the DURAVYU arm lost 40 letters. That appears to be due to the onset of a cataract and an epiretinal membrane unrelated to wet AMD. The second question might be: Were these eyes under-supplemented? Did our supplement criteria cause the result?

The answer appears to be no. Supplementation worked as expected. The top line of this graph on this slide represents the visual acuities of DURAVYU patients who received a supplement without the 9 asymmetric patients. You can see at top left visit prior to supplement, these patients had about a 3-letter gain in their vision. But at the supplement visit, they were minus 2 letters in their vision, which is about a 5-letter difference, which is exactly what we tried to capture in our supplement criteria. By the second visit post-supplement, the eyes were back to where they were a month prior to supplementation. The bottom graph is the patients in the 9 cohort who got supplemented.

It was only 6, and presumably, the other 3 did not get supplemented because the investigator deemed that the visual loss was not due to a VEGF-mediated disease, not due to wet AMD, and therefore, a supplement wouldn't help. In fact, the visual acuities at the supplement visit in these eyes were already down 14 letters. Notice what happened post-supplement, essentially no change in the visual acuity, confirming that this visual loss was not due to wet AMD. How about geographic atrophy? I already showed you the investigator's assessment of geographic atrophy. What you're seeing here is the reading center assessment in a masked fashion. At baseline, the two groups were evenly matched with geographic atrophy, 8% in DURAVYU versus 10% in control. At the end of the trial, no surprise, this happens in wet AMD eyes. There was progression of geographic atrophy.