EyePoint Guggenheim 3rd Annual Healthcare Innovation Conference

Sure. Yatin, first of all, thanks very much for the invitation. I think most people are aware that we were running two near-simultaneous phase III trials in wet age-related macular degeneration for our lead asset, DURAVYU. The first trial, LUGANO, read out in July. Second trial, LUCIA, read out in October. Unfortunately, and quite unexpectedly, both trials missed the primary endpoint, which was non-inferiority change in visual acuity at week 52, week 56, averaged compared to an on-label two milligram EYLEA control. The positive part of the study, of course, were the secondary endpoints, and we did very well with the secondary endpoints, which again made the primary result even that much more surprising. First of all, from a safety perspective, we treated about 450 patients with DURAVYU between these two studies, and we re-injected them.

The safety at week 56 included a re-injection in all patients. We showed that the drug continues to have a very, very nice safety profile, with really no concerns, and we believe that the read-through to diabetic macular edema, or DME, from a safety perspective, de-risks the DME results. Some of the mild asymmetries we saw in the safety really had to do with the fact that there were more active patients with wet AMD in the wet AMD trial in the DURAVYU arm than in the control arm, which was, I would say, intuitively obvious when you saw that there were more rescues in the DURAVYU arm than in the control arm. Obviously, we don't expect to see something like that in DME, nor would we expect to see something like geographic atrophy, which is an AMD-related effect.

The second thing that's encouraging is the control of the fluid.

The difference in the pooled data on OCT from the two studies at week 56 was only 10 microns, which is about the same difference, frankly, we saw in the phase II. 10 microns from a clinical perspective is not meaningful. Normal foveal thickness, or CST, on the OCT is about 325 microns, so you are talking about a standard deviation worth of change. That, again, quite encouraging that we were able to control the exudation quite well. Finally, both trials showed a near-identical reduction in the treatment burden after the load of, on average, two fewer injections in the DURAVYU arm. While maintaining vision is a prerequisite for approval, and improved vision, which we did show, by the way, both trials did show that DURAVYU could improve the vision, you want to see the added benefit of reduction in treatment burden.

That type of result also, we believe, is going to be a positive read-through to diabetic macular edema.

Correct. Again, to be fair, there was about two and a half times more floaters- Yeah in the DURAVYU arm, but it was under 10% in the pooled data.

When you look at the timing of that, remember, these are inserts. They are not a liquid being injected. It is probable that most of these safety events around floaters were the patients actually visibly seeing the inserts as they were injected or shortly thereafter. We have used inserts in retina for decades now, and patients do occasionally note that they can visualize them, but virtually never is it a concern.

Yeah, that is a good question. Just to recall, in the phase II, we enrolled only previously treated patients and had a quite positive result. The decision to enroll naive patients was several-fold. First of all, we believed it would de-risk the trial, and secondly, a broader label.

But in the end, when we looked at the results and broke it down by previously treated or naive, there really was not a big difference in the results. The previously treated patients did a little bit better, but not, again, statistically non-inferior given the size of that arm.

Yes. I'd like to add before we talk about the studies, if I could go into a little bit of the pathophysiology.