EyePoint, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Sure. First of all, thanks for having us. Yeah, so, as many of you are aware, we talked about our top-line results from LUGANO recently. I'd like to start out with the positives because I'm a positive guy. We did really well on the secondary endpoints. First of all, from a safety perspective, we were never concerned about the safety of the medication, but this was the first study in which we re-injected it, and so the safety looked really good even with re-injection. The second really positive aspect of the secondary endpoints was the anatomic control of the wet AMD. As you are probably aware, ophthalmologists, retina specialists, we look at OCTs to say, “Is there active fluid?

Is there not fluid?” At the primary endpoint of the trial, there was virtually no difference in the fluid in the central subfield thickness between our drug and on-label aflibercept, which was the control. So we had really terrific anatomic control. A reduction in treatment burden over 40%, after the load, which would correspond to approximately two fewer injections a year in the real world, which was excellent. When you looked at supplement-free rates, 76% up to six months, 54% up to a year. So over half the patients were successfully treated with our drug alone. When you look at other things like zero to one supplements at the end of the year, there was almost 80% of the patients in the DURAVYU arm had either zero or only one supplement. Remember, in the real world, if we're approved, a supplement's not a failure.

What doctors and patients want is a reliable way to reduce the treatment and the visit burden, keeping the anatomy and the vision stable. When you take another step and say, how about two supplements a year? Well, two supplements and two DURAVYUs is four injections a year, so every three months. We had almost 90% of the patients who were under control at four injections or less per year, which would, again, in the real world, would be tremendously better than anything we have right now. The elephant in the room, obviously, is we missed the primary endpoint. The primary endpoint, again, is non-inferiority change in visual acuity, measured from day one to an average of week 50 to week 56.

While we had excellent anatomic control and fewer supplements than expected, suggesting that the wet AMD control was really good, there was a real mismatch in the 15 letter losers between the DURAVYU arm and the control arm. What do I mean? Historically, if you look at 2-milligram EYLEA, whether it's VIEW 1, VIEW 2, way at the beginning, or any time 2-milligram EYLEA was used as a control, one would expect between 4%-5% of eyes losing 15 or more letters. In our DAVIO 2 phase II, 7.7% did. But in the phase III, it was only a half a percent, which is really unprecedented. When you look at the 4%-5% who lose 15 or more letters, some of those are eyes in which EYLEA just doesn't work.

There are eyes that have wet AMD, which even the monthly treatment, you can't control them. That's probably 1% or 2%. The other is eyes that lose vision for other reasons. These are elderly patients, and so they're going to get cataracts, they're going to get detached retina, they're going to get glaucoma, they're going to get geographic atrophy. The amazing part is in our control arm, there were none of those that lost 15 or more letters. That's really the mismatch. We've done some post-hoc analyses looking at that. One of them, what we did is we took all the 15 letter losers, and we said, you know what, let's just randomly divide them in half. What would have happened if they were randomly put into each group?

We did that 10 times, and each time we were non-inferior with the change in vision from -1.3 to -2.0 letters. What we're hopeful, looking ahead at the next trial, LUCIA, is if there is a regression to the mean in the control arm, then we are confident that we would be non-inferior. Moreover, we looked at these nine patients who lost vision in our arm, but primarily didn't lose it from wet AMD. Their wet AMD control was good. Why did they lose vision? One was a retinal detachment. There was only one retinal detachment in our arm. There was one in the control arm. The big difference is they were both successfully repaired with one operation, but the eye on our arm had never had cataract surgery. So that eye got a significant cataract right after the surgery, which is typical.

The eye in the control arm did have cataract surgery and wasn't going to get another cataract. That's the type of mismatch that unfortunately we saw. The other thing we saw was six eyes that lost vision due to geographic atrophy primarily. We've now, as of today, we've published some new findings on geographic atrophy, which I'd like to review.

Please. First of all, when you looked at 15 letter losers in the DAVIO 2 trial, which had about 100 patients treated with our drug, none of them lost 15 or more letters from geographic atrophy.

In fact, there was double the rate of 15 letter losers in EYLEA versus us in the phase II. Looking at the phase III, geographic atrophy was allowed in the trial to a certain degree. About 10% of the EYLEA eyes had it at the beginning, and about 8% of our eyes had it at the beginning. At the end of the trial at one year, it was 29% EYLEA versus 24% us. That's not statistically different, but numerically higher in the EYLEA arm.

suggesting that our drug does not cause new GA. The next question is how about speed the growth of GA? We looked at that as well, and historically, if you look at the studies on geographic atrophy, it's typically about 2 to 2.2 millimeters squared per year. Our rate was 1.7 millimeters squared per year, so under what is typical. The other way to really do it is to look at the fellow eye because it's almost like a self-control.

If you've got a patient that has geographic atrophy in both eyes, they tend to progress at the same rate, and that's what happened in our trial. It was 1.7 in the DURAVYU eyes, 1.6 in the fellow eye. So there's no evidence from that analysis that our drug sped the growth of preexisting geographic atrophy.

What we did find was that the geographic atrophy started closer to the fovea, approximately 800 microns to the fovea at the start versus 1,000 microns in the control arm. It progressed at the same rate, but it started closer. We think that that's the primary reason for the mismatch.

I see. We've gone back, and again, looked at a lot of different aspects of the safety and the efficacy in the data from LUGANO.