Ladies and gentlemen, thank you for standing by. Welcome to EyePoint Lugano topl ine data readout. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Dr. Jay Duker, President and Chief Executive Officer of EyePoint. Please go ahead. Thank you very much. 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 mg or on-label aflibercept control. This is the first study that looked at repeat dosing of DURAVYU. It was given every six months. The primary endpoint is one-year efficacy and safety. The studies are planned to go on for two years for safety. The primary endpoint of both studies is non-inferiority mean change in vision from day one 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 eight, the eyes that were randomized to DURAVYU got a DURAVYU injection about 30 minutes after their third EYLEA. DURAVYU was then redosed every six 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 eight 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 six 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 six 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 nine showed good anatomic control of their wet AMD, and six of these nine eyes received a supplement at some point in the study, but none of the supplementation improved their vision. These nine 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 nine asymmetric eyes are removed. Notice about five letter improvement that is maintained throughout the trial. The solid purple line is the visual acuities of the nine 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 nine 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 0.5%. 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 nine asymmetric patients. You can see at top left visit prior to supplement, these patients had about a three-letter gain in their vision. But at the supplement visit, they were - 2 letters in their vision, which is about a five-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 nine cohort who got supplemented. It was only six, and presumably, the other three 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. Numerically, however, it was higher in the control arm, and therefore suggesting that DURAVYU showed no trend of worsening of geographic atrophy. We conclude that neither the supplement criteria or any DURAVYU-induced AEs drove the primary result. How about the secondary endpoints? Let's talk about reduction in treatment burden first. Again, we had a 42% reduction in treatment burden. This averages to about 1.1 supplement injections per year in the DURAVYU eyes. But from a clinical perspective, if this drug is approved and available to clinicians, they might expect two fewer injections per year in their DURAVYU patients, which we believe would be an outstanding result for patients with wet AMD. The supplement-free rates demonstrate our potency and durability. Up to week 32, that is six months after the first DURAVYU, 76% of the patients were supplement-free, and 96% had received only one or zero supplements, with 99% getting two or fewer supplements. At the end of the first year, it was 54% supplement-free, with almost 80% getting either zero or one supplements. At week 56, almost 90% of the wet AMD eyes that were treated with DURAVYU were stable with two or fewer supplements. That is four injections annually or fewer controlled almost 90% of the wet AMD eyes. This slide shows you the subgroup analysis for the unsupplemented eyes in both DURAVYU and control. This was over half the population, 54%. You can see in this subgroup, DURAVYU was non-inferior to on-label aflibercept with only - 1.8 letter difference. Looking at the anatomic control, it was excellent, with only a 3-micron difference at week 56. This slide also helps to show that our supplement criteria appeared to be adequate. If you believe that some of these unsupplemented eyes were losing control on DURAVYU, then you would have expected the OCTs to get worse as the study progressed, and you can see that they didn't do that. They remained stable. Both stability in vision and stability in anatomy in over half the eyes with our drug alone. Anatomic control, you've seen these graphs already, but to just to reiterate, a 4-micron difference at week 56 with the typical sawtooth pattern that we see with every other month EYLEA and lack of a sawtooth pattern in DURAVYU. Safety. AE profile, we believe, confirms a favorable safety profile with repeat dosing. We had no cases of insert migration into the anterior chamber, no anterior chamber opacities, no free-floating drug particles were observed, no cases of retinal vasculitis, no cases of severe IOI, and in fact, as I already mentioned, there was only one case in each arm of IOI, and in the DURAVYU arm, it was treated for two weeks with topical medications and got better. Less than 1% rate of retinal detachment and endophthalmitis in each arm. There was a mismatch in floaters, but all cases of floaters were mild or moderate and didn't require treatment or have any impact on vision. As we previously reported, there was a low discontinuation rate of about 6% in each arm. This is the entire AE chart for all adverse events that occurred over 2%. As I mentioned, we had about 2.5 x the rate of floaters as aflibercept, but they really didn't cause any visual decrease. None of the patients reported wanting to have the inserts removed. Really didn't seem to be an issue with repeat dosing. We will be digging into that a little bit more, but based on the temporal association, we think that some of these floaters were probably visualization of the insert. Neovascular age-related degeneration, you'd expect with more supplements, we would have a higher rate, and that accounts also for the retinal hemorrhages, the retinal edema, and the subretinal fluid. Those are all events that one would see with active wet AMD. Notice again, though, cataract, intraocular pressure, dry age-related macular degeneration, no difference. What are our conclusions? First of all, we believe these results are clinically meaningful and potentially impactful commercially, if approved. While we didn't hit the non-inferior margin in the total population, we were non-inferior when we excluded this asymmetric cohort of nine eyes who experienced severe visual loss unrelated to wet AMD. We believe this study shows favorable safety profile with redosing. 42% statistically superior to standard of care reduction in treatment burden. 80% of the eyes could go up to week 56 with zero or one supplement, and the anatomic stability was excellent, with only a 4-micron difference, confirming both our potency and our durability. Why do we have confidence? First of all, we showed that half the patients could be supplement-free at one year with stable vision and OCT, which potentially means 50% of the wet AMD patients out there could receive just two injections a year of our drug showing stable vision and anatomy. This evidence gives strong potency data and durability data based on the OCTs. This is the first TKI to show a vision gain in phase III. In the totality of the results, we believe we have demonstrated the potential to change the treatment paradigm. We also have a lot of confidence in LUCIA. The strength of the ad hoc analysis and the secondary endpoints gives us confidence in hitting the primary endpoint and the secondary endpoints in the upcoming LUCIA trial. We expect to show that data in the fourth quarter of this year. If positive, we expect to engage the FDA in a discussion of our wet AMD data package, and we hope to submit that in the first half of 2027. We look forward to advancement of the DME program with both pivotal trials reading out in Q4 of 2027. Thank you very much, and happy to entertain any questions that you may have. Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question will come from Tess Ramiro with JPMorgan. Your line's open. Hi, Jay and team. Sorry to see this update this morning. Thank you for the wholesome presentation. I wanted to ask a regulatory question here. What are the pushes and pulls that we should be thinking about around approvability potential as we think ahead, and your expectations of file in the fourth quarter? Is it the case that you will need two positive non-inferiority trials to file? Then I have one follow-up. Yeah. We don't believe that will be necessary. As I'm sure many of you are aware, there are at least two instances that we're aware of in the ophthalmic division of the FDA, where there were approvals of a drug with one phase III that was positive and one phase III that was negative, the Apellis drug and Outlook. There are a myriad of other studies like this, outside of ophthalmology with approval. Also, remember that just a few months ago, the agency updated their guidelines around single trial approval. What was important with the single trial is supportive results on distinct pre-specified secondary endpoints. I think we showed that. Consistency among the subsets. I think we showed that. High-quality conduct with missing minimal data and a mechanistic MOA that directly targets the major driver of the pathophysiology. I think if LUCIA is positive, we're going to have a strong package to submit to the FDA. We are confident that if LUCIA is positive, that the FDA will look very favorably on the package. Okay. Just as a follow-up here, what gives you confidence that you won't have a confounding cohort in LUCIA as well? Well, I think, again, looking at the data, having eyes in an elderly population that lose vision from geographic atrophy, which is unrelated to wet AMD therapy or other diagnosis, is not unusual. Having none of them in the control group is highly unusual. Again, those type of diagnoses, additional anti-VEGFs don't stop glaucoma. They don't stop the cataract after retinal detachment repair. What we would expect is not that these would not occur at all in LUCIA, but they would be balanced. Had they been balanced, then we would have hit the primary. I didn't show a slide on this, but we've already done an analysis like that, where if we had taken all the 15 letter losers and just split them evenly between the two arms and did that randomly, and we did that over 10 x randomly, and each time we were non-inferior. We believe that it's likely that this was due to chance alone and that we won't see a similar split in LUCIA. Beyond that, if you just look at the efficacy and you look at things like the control of the anatomy, our drug did a great job controlling it. If you look at the supplement free, 54% were treated with our drug alone, with non-inferiority change in visual acuity and excellent control of the anatomy. We have a highly potent drug that is durable and that, if approved, we believe doctors will welcome its use, and we believe this can really help a lot of patients if approved. We're going into LUCIA with a lot of confidence. Thanks, Jay. Thank you. The next question will come from Faisal Khurshid with Jefferies. Your line is open. Hey, guys. Thank you so much for taking the question. Can you just confirm the outcome on the primary endpoint, including what the bottom range of the confidence interval was for BCVA in the ITT population? I am going to ask our Chief Medical Officer, Ramiro Ribeiro, who is here with me, to comment on those numbers. Hey, Faisal. So when we look at the full analysis set, including all patients, the difference in BCVA was about 3.8 letters, and the confidence interval crossed the 4.5 letter at about 5.7. What is very interesting is when we remove the nine patients, again, this is only 4% of the patient population, the difference between the groups is 2.4 letters. So those 9 patients represent 1.4 letters. And then we are below the 4.5 confidence interval for the non-inferiority. So again, I think this represents compelling evidence that the effect of those 4% patients driving the results. And then one very interesting analysis that we have done also, instead of looking at the mean change, we look at the median change. Again, with that type of analysis, we also observe the impact of these extreme values. And then with the media analysis, we also show non-inferiority against only aflibercept. Got it. Thank you, Ramiro. Just as a follow-up, does that mean that for that 2.4 number, the bottom end of the confidence interval for that was pretty close to 4.5? If so, how should we think about that going into LUCIA, considering that past precedent and what AMD has shown variability between identical trials? Thank you. Yes. I wouldn't call it very close. I think the lower limit was around 4. I don't think that's very close. If we get that result in LUCIA, that would be favorable. Great. Thank you for clarifying. Thank you. The next question will come from Yatin Suneja with Guggenheim. Your line is open. Hey, guys. Thank you for taking my question. Thank you, Jay, for walking us through in details. Definitely those nine patients, a little bit unlucky on those nine. Remarkable control on OCT. The question I had for you is, maybe just repeat, if you could, when physicians treat, what is more relevant to them? Is it the OCT or the BCVA? With regard to the FDA, are you going to have an interaction with them before the next study reads out, just to get a sense of how they might be handling these nine patients? If at all, would love to sort of get some clarity on the FDA front, how they will treat this study, in terms of those nine patients. What about the previous DAVIO studies, right? Could those be used as a supporting evidence, even though the patient population was different? If you can maybe just sort of frame the full package for us. Thank you. Sure. Let me work my way backwards. Yes, the full package will get submitted, DAVIO 2 will be confirming evidence, especially vis-à-vis the safety. The second question you had was about regulatory interaction. It's too early to really have a clear pathway. Obviously, we've been working diligently over the last few days since the study was unmasked to understand the results. We will, in the future, have a more clear path and discussions with the FDA. But it's too soon to know that. As for how we treat in the real world, I think Tarek Hassan. Tarek, if you're here, can you say hello? Are you on the call? Yeah, I am, Jay. Yes, I am, absolutely. Tarek, so you're obviously still a highly regarded, very busy practicing retina specialist. The question was, when a patient comes in for a visit with wet AMD, what's more relevant to you, anatomic control or visual acuity? Well, it's obviously both. When we think about the things that we can control within the bounds of a treatment that we may have in our hands, it's ultimately really the anatomy that we have the most impact upon that. So we deliver the drug to do the best we can with the disease at play, in this case, wet AMD. So we want to dry the eye as much as possible. We want to control the growth of the wet AMD lesion. We hope it translates into a visual improvement, which it does in most cases when the primary driver of vision loss is that. Of course, we care about vision. It's just that so many other confounding things, like we saw in this trial, for example, can affect the vision, and that's out of our hands. We wish we had more drugs and more therapies for these other things. But in short, we care about both, but we have in our hands something that we can try to fix anatomy, and we hope the vision correlates. Thank you. Thanks, Yatin. Any other follow-up for you? No, I'm good. Thank you. Okay, great. Thank you. The next question is going to come from Steve Seedhouse with Cantor. Your line is open. Great. Thanks so much for taking the questions. I have two. The first one is, are you planning to amend or update the statistical analysis plan in LUCIA just to pre-specify this type of secondary analysis, excluding these etiology patients, just to build some prospective sort of credibility for the case that you'll ultimately make to the FDA? I'm going to ask Ramiro to answer that question. Yeah. Thanks, Steve. I think it's very fair to take some learnings from the phase III study and then apply for an upcoming phase III study readout. We're certainly going to spend the next two months looking into the LUGANO data, try to learn as much as possible so that we can apply any learnings into the LUCIA readout. Okay. Thank you. Jay, I think I heard you mention in response to a prior question that the margin for the confidence interval was about four letters, associated with that 2.4 letter difference in that ad hoc analysis. But when you exclude the nine patients, obviously, that are outliers, presumably that reduces the variance quite a lot in that subgroup. So how much did that affect sort of that four letter outcome? And when you did that simulation, I think you mentioned splitting up those nine patients across the two arms. In those 10 simulations, how close does the non-inferiority margin get to the 4.5 letter threshold? Yeah. Good question, Steven. Again, I'm going to ask Ramiro to address them. Yeah. Let me just recap it first. On the full analysis set with all patients, the difference between DURAVYU and aflibercept was 3.8 letters, and the lower bound of the confidence interval was 5.7. Once we removed those nine patients that lost vision not because of wet AMD, then the difference between DURAVYU and aflibercept was 2.4 letters, and the confidence interval, the lower bound was four letters. Once we did all those simulations that Jay referred to, where we split in half the patients that lost 15 letters. Of course, varies a little bit, but then the confidence interval for all those 10 simulations was less than 4.5 letters, as low as 3.7. But of course, on those 10 simulations, it varies a little bit. Thank you very much. Thank you. Our next question will come from Yigal Nochomovitz with Citigroup. Your line is open. Yeah. Hi. Thank you for taking the question. I wonder if you could spend a little more time just explaining the mechanics of how you came to identify these nine patients that contributed to this highly asymmetric analysis. Can you just walk through what the process was there to find them? Can you also talk about what you plan to do with respect to any pooling of data for these two studies, assuming LUCIA is positive. What types of pooled analysis might we expect when LUCIA reads out? Or would that only be later? Thank you. Sure, Yigal. We are happy to address both. When we first took a look at database lock of the masked data, overall, the group showed about a 3% or so rate of 15 letter loss, which is right in line with what we would have expected and maybe even a little lower than what we saw historically in these trials. When we unmasked, of course, we realized that the 15 letter losers were highly asymmetric and mostly in our arm. We did an analysis of them, including the 15 letter loser in the EYLEA arm, which was, first of all, was this 15 letter loss due to continued activity of wet AMD? The answer was very few. The second group was, did these patients lose vision due to wet AMD even though the control was good? The answer was, again, very few. That happens. You can control the anatomy, win the battle, and lose the war because of various reasons. But in those small number of eyes, I believe it was three, the anatomy was well controlled, but the visual loss was due to wet AMD. The other nine eyes, of which there were none in the control arm, lost vision with well-controlled wet AMD due to other things. Six, again, geographic atrophy, two due to glaucoma, and one due to the detached retina that while was reattached, had significant decreased vision due to cataract and epiretinal membrane. Looking at the GA patients, and we have shown them to some KOLs now already, and I think they agree that all of them had GA at the beginning of the trial. We will be looking more closely at the progression and the progression of GA, not in the 15 letter losers, but in the other patients to try to determine was there asymmetry or not. But at least on a population basis, based on the reading center assessment of geographic atrophy and the investigator's assessment of dry AMD, there does not appear to be a difference between the groups, and in fact, on a numerical basis, we noted higher numbers in the control arm. I think your second question was about pooling, correct? Yeah. Ramiro, do you want to answer that one? There you go. As part of any NDA submission with two phase III studies, one of the ask is always to pool the two studies together to again show the consistency of the results. Then you submit to the FDA. When we think about LUGANO, as Jay mentioned, we unfortunately have those nine patients. But other than that, the data looks very consistent. It makes sense clinically on how those nine patients behave and how they affect the data. So if LUCIA is successful, then we would certainly pool the data to show the overall benefit of DURAVYU. Okay. I am just curious, have you done sort of the downstream calculation, figure out what you would have to show from a lower bound of the non-inferiority confidence interval and the point estimate for BCVA in LUCIA, such that when you take the ITT populations for both studies on a pooled basis, you would generate an overall positive result globally for both trials. Is that a calculation you have done or plan to do? I think we need to look into that a little bit more. We do not have that precise calculation at the moment. I think you can look at a range which would be positive, but we do not have those exact numbers right now. All right. Thank you very much. Thank you. Our next question is going to come from Graig Suvannavejh with Mizuho. Your line is open. Thanks for taking my question. I'd like a follow-up if I could. I don't believe we've touched upon the debate around the contribution of treatment-naive patients versus treatment-experienced patients. Were you able to see anything within those nine patients that could be attributed to this difference? If you just comment on that dynamic. Then a second question is probably a bigger picture question, which is, given this data set and maybe given the data set from your rival competitor with their first phase III data, how should we be thinking about overall the TKI class? Any thoughts on how maybe differently or not you're thinking about this class in general? Thanks. Sure. The second question I think I'll take first, which is TKIs work in wet AMD. This is now, I believe, the ninth trial that has confirmed that there's biologic activity, durability, and the ability to control the anatomy using TKIs. If there are multiple TKIs that are approved, I think that there's certainly room in the market for that, but I would think that label and safety are going to be the things that would set us apart. I think that based on the safety that we've shown and the potential for label, since obviously we went up against on-label Eylea, I think that that would have the ability to set us apart. Your first question about the breakdown. In the nine patients, six of them were naive and three of them were previously treated, which is obviously consistent with the whole cohort. When we did subgroup analysis of the whole cohort, there was not a big difference in the result between the naive or the previously treated. We don't think that one group necessarily drove the top-line results. Thank you. The next question will come from Annabel Samimy with Stifel. Your line is open. Hi, everyone. Thanks for taking my question. I want to clarify one point. Can you just tell us the treatment burden reductions and the rescue-free rates, this was based on the total population or also excluding the asymmetry? Separately, given, there's always been a little bit of subjectivity in BCVA related to various reasons. To what extent does FDA weigh anatomical control of wet AMD more so than BCVA, and are there examples of this in past wet AMD studies beyond the TKIs? I know that KOLs value OCT tremendously, but I'm just curious to know how FDA treats OCT and weighs it against. BCVA in this kind of scenario. Sure. The first question was the secondary endpoints. All of those secondary endpoints that we showed you included the nine eyes, including the supplement three subgroup analysis. The nine eyes were included. Of course, only six of them, I'm sorry, three of them had not been supplemented. So that 1.4 letter difference you saw in the non-supplemented eyes between us and the control group would have been 1.1 letters if those three outliers were not included. But to answer your question directly, all the subgroup analysis was the entire population, including the nine. The FDA, really since the beginning of OCT 30 years ago, has said that anatomic endpoint for diseases like DME and wet AMD is a secondary. It's not the primary endpoint. But it needs to corroborate things. I mean, the FDA understands what the anatomy control means. There isn't a direct necessarily correlation between visual acuity and anatomy. There is a correlation, but it isn't one-to-one. Therefore, it's strong corroborating evidence that we have potency and durability to show this type of an anatomic result. But that in and of itself doesn't get us to approval. Okay. All right. Thank you. Thank you. The next question will come from Debanjana Chatterjee with JonesTrading. Your line's open. Hi, thanks for taking my question. I have a couple. Were there any additional DURAVYU arm patients with sub 15 letter losses, I mean, like between 8 - 14 letters that can be attributed to the same non-wet AMD etiologies, who fell below the cohort threshold and remained inside the 202 patients that excluding the asymmetric cohort comparator line? Debanjana, thanks for the question. Excellent question. We haven't had time to analyze that yet, but we certainly will. Sure. Can you also confirm the six patients who did receive supplemental injections with no visual acuity improvement, was the OCT fluid confirmed fully resolved and stable at the visit immediately preceding each of the patients' vision decline, or only at some point during the follow-up? I don't know the answer to that off the top of my head about the presence or absence of fluid before. I believe in the geographic atrophy patients, at least some of them did get a supplement, and early in the trial, it may have been due to active wet AMD, but not at the end of the trial. That is, again, we're going to need to go through carefully and look at each of those cases. To answer the question, I think what you're getting at is were some of those nine supplemented for wet AMD? I think the answer is probably yes. That didn't lead to the visual loss because the control was excellent. Sure. I have one last follow-up. Do you see any read-throughs to COMO and CAPRI trials in DME? Is there any changes you would implement to the trial design there? Well, certainly no trial design changes. I do not think that trial design played any role here. I am even more optimistic about our role in DME. There is no geographic atrophy in DME. That does not happen. You do not expect to see any kind of asymmetry there. Our phase II DME visual results were even stronger, and OCT results are even stronger. So that I think this really de-risks the DME diagnosis even more because look at the safety. Look at the efficacy with respect to treatment burden. Look at the efficacy with respect to anatomic control. All of this points to a potent drug with durability that is safe. All of that, in my mind, in our mind, really de-risks the DME program. As well, frankly, as we have said already, de-risks the LUCIA result. Appreciate the insights. I will hop back into the line. Thank you. Thank you. The next question will come from Yale Jen with Laidlaw & Company. Your line is open. Good morning, and thanks for taking the questions. I would just like to get some sense of any difference in terms of a patient baseline or other characteristics. For example, where the patient was enrolled and treatment-naïve versus treatment-experienced between the LUCIA and the LUGANO studies, so we get a better sense of any expectational handicap. I am going to let Ramiro talk a little bit about baseline imbalances and whether there is anything necessarily that might be gleaned about LUCIA. Yeah. First, on the LUGANO study, as Jay mentioned, we saw some small imbalances at baseline on BCVA, but those get adjusted in the model and didn't have an impact on the primary endpoint. The LUCIA study in comparison to LUGANO, the study design is very similar, exactly the same. The only difference is that we had in LUGANO 100% of the patients coming from the U.S., LUCIA, 80% U.S., and then 20% outside of U.S. So in terms of baseline characteristics, and we presented this at a conference earlier this year, we should expect them to be similar between the two studies. Okay, great. That's very helpful, and best luck for LUCIA. Thank you. The next question is going to come from Lisa Walter with RBC Capital. Your line is open. Oh, hi. Good morning. Thanks for taking our question. Maybe a couple here on LUCIA. Jay, if you plan to file with LUCIA alone, could the FDA require a more stringent non-inferiority margin for one trial versus two? Then just on the rescues, wondering if you can give us a little bit more color here and give us a sense of the cadence of rescues, if they are occurring closer to the start of the trial or maybe closer towards the end, towards the primary endpoint. Any color here would be helpful. Thanks so much. Yeah. First of all, I don't think there's anything to suggest that one trial versus two changes a non-inferiority margin. Statistically, that wouldn't make any sense. I don't think there's any data that would suggest that. As for the cadence of the rescues, we talked about this going into the trial, that the top line primary endpoint was going to be total patient population, but the FDA has asked us to do sensitivity analyses around the rescued eyes. None of the sensitivity analyses was there a higher penalty paid for late rescue versus early rescue. We haven't done a real analysis on that yet, and frankly, I'm not sure it's really going to be helpful to do so. I think you can glean from the number of eyes that only received one rescue at 8 months versus the number of eyes that only received one rescue at 56 weeks, that there wasn't a lot more rescues weighted towards the end. But again, not sure that data is anything that either the agency or anybody should make any deal about. If there are no further questions, then I'd like to conclude with just a few more remarks. First of all, while obviously the totality of the result was not exactly what we hoped for, DURAVYU showed that it's got the potential to change the treatment paradigm in wet AMD. The safety is strong. The anatomic control was terrific. Over half the eyes were controlled through the end of the first year exclusively by DURAVYU. In those non-supplemented patients, they were non-inferior to on-label EYLEA. As we really look closely to all of these results, we remain highly confident that DURAVYU has the potential to evolve into tomorrow's standard of care. I want to thank all the LUGANO investigators and the patients who entrusted us to preserve their vision. I also need to thank our team here at EyePoint. They are extremely talented and hardworking, but I especially want to mention Ramiro's clinical team, Robin's IR team, our IT team, and our entire executive committee, who really performed at the highest level with the unmasking of the data. We have a lot more to come, and we're really optimistic about the future. Thanks, everybody. This concludes today's conference call. Thank you for participating, and you may now disconnect.