EyePoint, Inc. (EYPT) Earnings Call Transcript & Summary

Good day, ladies and gentlemen, and welcome to EyePoint Pharmaceuticals Data Call at American Academy of Ophthalmology. [Operator Instructions] I would now like to turn the conference over to your first speaker today, Mr. George Elston, CFO. Sir, the floor is yours.

Thank you, and thank you all for joining us on today's conference call to discuss our positive top line safety and efficacy results from the Phase I DAVIO trial evaluating EYP-1901 for the treatment of Wet AMD. I am George Elston, the CFO of EyePoint Pharmaceuticals, and with me today is Nancy Lurker, President and Chief Executive Officer; Dr. Jay Duker, Chief Operating Officer; Dr. Dario Paggiarino, Chief Medical Officer; and Dr. Carl Regillo, KOL and Chairman of the company's Scientific Advisory Board. Earlier this morning, we issued a press release detailing our results. We are using slides to accompany our remarks today, which will be found in the Investor Relations tab on the corporate website, www.eyepointpharma.com, along with a replay of our webcast, shortly after our call ends. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, financial projections and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is filed with the -- and on file with the SEC, and in other filings we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals.

Thank you, George. Good morning, everyone, and thank you for joining us. Today, we are excited to discuss our positive top line DAVIO Phase I Data Trial of EYP-1901 in Wet AMD patients showing positive safety and positive efficacy signals across a range of key parameters. These data were just presented this morning by Dr. David Boyer at the Retinal Subspecialty Day of the American Academy of Ophthalmology 2021 Annual Meeting. These results today bring us one step closer to changing the standard of care for patients by offering an in office sustained delivery treatment option with the potential for -- to every 6-month dosing. Before we discuss the data, I'm going to provide a very brief overview of our company and our lead product candidate, EYP-1901. Then I will turn the call over to Dr. Jay Duker, who will discuss our clinical results in detail. We are also pleased to have Dr. Carl Regillo, Chair of Eyepoint Scientific Advisory Board join us today. He's a renowned ophthalmologist and retinal specialists, who will share his perspective on the data on today's call. So turning to the first slide. We are very pleased, especially now with our positive DAVIO readout that we have a compelling pipeline focused on retinal disease. EYP-1901 will advance into Phase II trials for Wet AMD, diabetic retinopathy and retinal vein occlusion after the positive Phase I top line results were read out today. YUTIQ50 is our potential 6-month treatment for posterior uveitis and that is entering Phase III, and it does support a sNDA filing. And then we continue to have additional molecules and mechanisms of action under evaluation. Now as you all know, we have our Durasert technology, which is what we use in our DAVIO trial, which is a proven intravitreal drug delivery platform, and it continues to perform. It provides nice sustained local drug delivery, it's constant zero order kinetics, which provide a stable release of drug in the eye over weeks, months or years. And now it continues to be safely administered to thousands of patients' eyes. This was reinforced by the DAVIO trial and across 4 FDA approved products. And then finally, we have our commercial franchises, YUTIQ and DEXYCU, and our 2021 net product revenues are improving as the COVID-19 restrictions are eased across the US. And now I'm going to turn the call over to Dr. Jay Duker, our Chief Operating Officer, to review our top line Phase I results in detail. Jay?

Thank you, Nancy. Before I discuss the DAVIO Phase I data, I'd like to share some brief background on this trial. We were granted a safe to proceed by the FDA in December of 2020. We enrolled our first patient in January of 2021 and then successfully enrolled the entire trial in under 4 months. This is a tribute to the terrific team assembled at EyePoint. As most of you know, I became a full-time employee of EyePoint just 2 weeks ago, and I've been asked by many people why? My answer is simple. The people, the culture and the technology. I want to acknowledge our CEO, Nancy Lurker, who had the vision to see what EyePoint could become and have the skills to assemble the team who's making it a reality. On to the depth. I think most of you know that we have excellent FDA-approved anti-VEGF medications that are both safe and effective. The problem is they don't last very long. This slide illustrates what happens in the real world. There's a robust improvement in vision typically in the first 3 months. But in the real world, much of that vision is lost by year one. This is another study that just came out a couple of months ago, that looked at the effect of missed visits during COVID. Patients who are getting anti-VEGFs who did not show up for their visits due to COVID lost vision and some of them lost vision with a delay of just 5 weeks. Sustained release options may give practitioners and patients improved outcomes in such circumstances. We have a novel approach to Wet AMD therapy that we call EYP-1901. It's vorolanib and Durasert, bioerodible. Vorolanib is a small molecule tyrosine kinase receptor inhibitor with activities against all isoforms of VEGF and PDGF. It has been previously studied as an oral agent in 2 Wet AMD trials, Phase I and Phase II. There were strong efficacy signals, but systemic toxicity halted the Phase II trial, but there was no ocular toxicity noted. We've put vorolanib into a bioerodible form of our Durasert implant. This is similar to YUTIQ, RETISERT and VITRASERT, but the main difference is no polyimide shell, which allows it to be bioerodible. The drug release dynamics show an initial burst due to drug at the surface of the implant, followed by constant zero order kinetic release for months. And you can see here a picture of one of the implants in one of our patients' eye. We believe we'll get effective blockage of all isoforms of VEGF, because we lock at the receptor level. So on to the Phase I trial results. This is the key take-home messages from the Phase I interim data. All objectives were successfully met. We have positive safety data with no ocular serious adverse events reported, no drug-related systemic serious adverse events reported. All the ocular AEs were Grade 2 or less except for one, Grade 3, which was not drug-related. It was progression of disease. We'll also show you some positive efficacy data. Stable visual acuity in OCT, which is what we would expect in a previously treated wet AMD population, with a median time to rescue of 6 months, we'll also show a clinically significant reduction in treatment burden. This study outlines the structure of the Phase I trial. It was open-label, dose escalation, no control arm. There were no mandated EYP-1901 retreatments in this trial. We enrolled only previously treated Wet AMD patients, but we had no exclusion for disease activity or presence of fluid with the exception that after their initial standard of care injection at 1-week visit, they couldn't have an increase of 50 microns of fluid. Now this is important to note about the way the trial was structured. At the screening visit, all patients received the standard of care injection whatever they have been receiving prior. 7 to 10 days later, they got EYP-1901. We're showing you interim results of 6 months, we have 4 dose groups, the low dose 440 microns, which had 3 patients, the low mid dose, approximately 1 milligram with 1 patient, the mid-dose 2 milligrams with 8 patients and the high dose 5 patients approximately 3 milligrams. This is the characteristics of the participants, along with some follow-up. This is what you would expect for such a Wet AMD trial, more women than men, best corrected visual acuity mean about 69 letters, mean CST, almost 300 microns. And this was a fairly heavily treated group, on average, 8.76 injections per year prior to enrollment. We are really proud of the follow-up, despite COVID out of the possible 170 visits, patients made 168 or 99%, also attribute to our investigators and their team. So let's look at the safety results now. We had no ocular serious adverse events, no drug-related systemic SAEs. In addition, there were no reports of vitreous floaters, no endophthalmitis, no retinal detachments, no implant migration in the anterior chamber, no retinal vasculitis, no posterior segment inflammation. We had 1 eye that developed mild iritis or anterior chamber cell and flare. It occurred 2 weeks after EYP-1901, but also 3 weeks after a standard of care injection. It was treated with a mild steroid drop and resolved in 8 days without sequelae. And I might add, this was asymptomatic, patient was not aware. We also had 1 eye with an asymptomatic vitreous hemorrhage from the injection, the hemorrhage was observed, and there was no alteration and visual acuity. This slide shows all the ocular AEs to date. At the top is the AEs of particular interest. We did have 3 patients with reduction in best corrected visual acuity due to disease progression. Here are the results. Since this was a previously treated population, and we know all the visual acuity gains in Wet AMD are typically made in the first 3 months, we would have expected and hoped for stability, which is what we got. For all 17 eyes at 6 months, the visual acuity was minus 2.5 letters. Now notice, in some of the graphs, as we broke it down by dose, there's a fluctuation, and that's due to the need for rescue. This is the alterations in CST, Central Subfield Thickness. And again, we would expect stability in an adequately treated population, and that's what we got. The mean CST was a reduction of 2.7 microns at 6 months. Again, there is some alterations in some of the dosing cohorts, notice again the sawtooth pattern in the low dose. This was caused by a patient who required rescue at month 1. And as I will show you, we enrolled 3 patients with very severe disease who required rescue at month 1. Notice, those 3 patients not only were not well controlled by EYP-1901 at month 1, they were not well controlled by standard of care, which they had received 5 weeks prior. This graph shows the rescue free rate up to each visit, up to month 4 76% of the patients were rescued free, up to month 6, 53% of the patients were rescued free. The median time to rescue is 6 months. And at this moment, we still have 8 out of 17 patients who have not been rescued. This breaks down rescue free rate by dose. The black bar of 100% looks terrific. But remember, that was just 1 patient, who still has not been rescued. This chart shows you the reason for first rescue. And again, I'd like to highlight, 3 of the patients, 1 in the low dose and 2 in the high dose group required rescue at month 1. So they not only were not well controlled by EYP-1901. They were also not well controlled by standard of care. This is unusual. My colleagues can tell you that most patients would -- under our rescue criteria would not have needed another standard of care injection after 5 weeks. However, this speaks to the fact that we allowed virtually all patients with Wet AMD to be enrolled. This is the swimming lane plot that shows the significant reduction in treatment burden after EYP-1901. We have data for approximately 1 year prior to enrollment. We normalize the data to show for each patient, what was the average number of injections they received on a monthly basis prior to enrollment. And then what did they receive for the 6 months after enrollment. And you can see for the entire cohort, we had a 79% reduction in treatment burden. The only patients that required more than 1 rescue for the first 6 months were the 3 patients who had to be rescued at month 1. All the other patients received just 1 rescue treatment. We break it down also by different dosing. You can see that on the right. And here it is by doses, the low dose, medium, again n equals 1, mid dose, and high dose. This shows it another way, 79% reduction in treatment burden, which we believe is highly clinically relevant. And by each of the dosing cohorts. Let me show you a couple of the patients now. This is a patient who was diagnosed with Wet AMD 9 months prior to enrollment. And you can see on the left that OCT at the time of diagnosis, the patient had received a total of 6 anti-VEGF injections prior to enrollment in our study, and you can see a time of enrollment on the right patient was fluid free. This is the 1-month visit. No rescue, fluid free, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months. This patient has now gone 9 months with no significant change in CSD or visual acuity has not been rescued. Let me show you one of the eyes that require rescue at one month. This patient would be considered a failure of both EYP-1901 and standard of care therapy, this is how the eye looked prior to treatment at screening. Notice, a large pigment of field attachment, a lot of intraretinal fluid, subretinal fluid hard exudate, a very active eye. This is the patient at 1 month. And if you look at the central SIS, the intraretinal fluid, they've actually increased 5 weeks after an EYLEA shot. The patient got rescued at month 1. At month 2, they were practically dry. Month 3, fluid was back, got rescue number 2, month 4 dry again, month 5, fluid is back, month 6, dry. So even though this patient required 3 rescues over 6 months, including 1 at month 1, EYP-1901 in a sense is a combination therapy, if you will, in this patient, still reduce the treatment burden by about a third. Let me show you a third case. This patient entered the study with subretinal fluid prior to treatment. This is after 8 anti-VEGF injections. This is month 1, no rescue, month 2, no rescue, month 3, you can see the subretinal fluid has returned at the temporal side of the pigment feel detachment, but no rescue. Month 4, only a sliver of the fluid is left. Month 5, even less and month 6, practically dry. So we believe this type of case may actually change the paradigm for retina specialists. If you were treating such a patient with a single injection at month zero with a standard of care injection, one would assume that since month 3, there was no fluid and the medicine was out of the eye that this patient wouldn't require another injection. But because we have what we believe is true sustained release, this patient did not require rescue injection and the fluid did dry up. So again, to summarize, all Phase I clinical trial objectives were met. We have positive safety data, no ocular SAES, no drug-related systemic SAES, the ocular AES, the majority were mild and to be expected. Efficacy stable visual acuity in OCT across all 17 patients, median time to rescue is 6 months, 76% of eyes were rescue free up to 4 months, 53% rescue free up to 6 months and a significant clinical reduction in treatment burden by almost 80%. We're also showing a durability of response with 8 of the 17 eyes still rescue free as of today. And 1 eye, as I showed you, is now out 9 months. We believe this shows proof-of-concept for Vorolanib as a therapy in Wet AMD. So the summary of clinical findings, favorable safety and tolerability profile for EYP-1901, proof-of-concept for significant activity of Vorolanib in the Wet AMD setting and a demonstrated ability for Durasert technology to deliver controlled extended-release of active drip over months in a bioerodible forum. This implies a highly significant improvement to the dosing frequency relative to standard of care, if we continue to show it in subsequent trials. So what are our next steps? We're advancing EYP-1901 into 3 Phase II clinical trials. Wet AMD should initiate expected by 2022, diabetic retinopathy also in 2022 and retinal vein occlusion by 2023. We have asked for and will be meeting with the FDA for a Type C meeting next month. We would like to be further informed about our clinical trial development to speed our pathway to pivotal trials and hopefully, eventual FDA approval. We're going to use the clinical findings and the observations around biomarkers from DAVIO to help refine Phase II clinical trial design. Now what do I mean by that? This is an example of something that we might do. I'm certainly not saying we will do, because remember, our last patient got their 6 month visit only 4 days ago. So we're still at the very early stage of evaluating these OCT biomarkers. We had 4 patients enter the study with intraretinal fluid in their central foveal [ caught on ] OCT. And we all know intraretinal fluid portends a poor prognosis for vision. So if we did an analysis without those 4 patients who presented with intraretinal fluid at screening, the end of the study would have been 13, but look at the rescue free rates. 100% of eyes could go up to 4 months that didn't have intraretinal fluid, 92% at 5 months and almost 70% at 6 months. This is what the post hoc analysis would show for those 13 patients who did not have inter retinal fluid, look at the swimming lane plots now without the patients also who required rescue at month 1, a substantial reduction in treatment burden. So we believe that this is a paradigm-shifting potential and Durasert in its bioerodible form has demonstrated that it can deliver small molecule agents successfully to the post year segment. We're looking at different molecules and different mechanism of action. We think we can tailor and control the dosing frequency for different indications in patient populations and we can also inject multiple implants simultaneously. Our focus is on executing these multiple clinical trials for EYP-1901 in the next year or 2, and we expect to apply this new technology enhancement to further expand the scope and scale of new indications. I'm going to stop now, and I'm going to leave this slide up, because we believe this is the most compelling data from DAVIO, the clinically significant reduction in treatment burden. I'd now like to introduce my colleague, Carl Regillo. Carl is the Director of the Retinal service at the Wills Eye Hospital in Philadelphia. He also is the Chair of our Scientific Advisory Board. Carl is an excellent clinician and surgeon. And he's one of the most well-respected Retinal specialists in the world. Carl, can you give us your perspective on the data you just saw?

Sure. Thanks, Jay. Happy to be here. I think it's really very exciting. It was just at the meeting to see it presented. In fact, I presented the data. So we see in all this now come together, and I'm really encouraged with what we're seeing here. I think the evidence looks strong. And I think this validates the TKI, tyrosine kinase inhibition is an established validated pathway for treating wet AMD. I'm particularly encouraged by the safety data. And you're right, when you look at these [indiscernible] plots, we get a nice sense of before and after, before the therapeutic intervention with EYP-1901. All these studies, especially Phase I and when you're dealing with previously treated patient populations, they're biased towards high need. Those are the patients most motivated and investigators are most motivated to want to introduce sustained delivery, and that's what this is. So we see the baseline characteristics, very frequent injections for all these patients. And mostly good response because at baseline patients for acute on average was good, a mean number of treatments up at 9 annualized. So we're treating these patients very frequently to establish and maintain disease control. So now we introduce EYP-1901. And what I -- the way I look at it, sort of top-level here is, only 3 out of 17 showed a response that doesn't necessarily indicate a great disease control, but the rest are definitely showing us a clear benefit with the introduction of EYP-1901. And those 3, you're going to get those high need patients, something we call them practice and suboptimal responders when you see exudation 4 or 5 weeks after an injection. And so those are particularly aggressive cases. But the rest pretty much cut through the spectrum of patients we manage in practice, and we're seeing excellent exhibitive control with a great reduction in the need for rescue or standard injections with our anti-VEGF biologics in the first 6 months. Pleased to see median time to retreatment at 6 months, and the majority of our patients getting these 4 months. When we start to get over 4 months into 6 or beyond, as you show it some great cases, that's true sustained delivery. Nothing even emerging, and I presented the [ Prisma ] data, that's 45% obtaining about 4 months of treatment. So this exceeds the standard paradigm of what we're doing and what we're about to do. You can't argue against the great safety profile with no serious ocular serious adverse events in only 1 case of very mild iritis. I'd always like to see the individual cases. Cases 1 and 3 were very, very impressive. And we've seen that in some of the other TKI programs. And so it's great to see it here, too. I like case 3, in particular, because I have a lot of experience with port delivery. And we'll see little fluctuations in fluid as time goes on, but we're seeing excellent control overall. And you can't argue against case 1. In case 2, again, occasionally, you're going to get a super aggressive type of patient with wet AMD. And in practice, we struggle with those. In fact, those are the types of cases you'll see investigators on the podium talk about needing to treat even every 2 or 3 weeks sort of before the 4-week standard.

Thank you, Dr. Carl Regillo, very much, and we appreciate you taking the time today out of what I know is a very demanding schedule that you keep. So in summary, and based on the data discussed today, we remain excited about EYP-1901's potential and looking forward to entering our Phase II trial. I appreciate everyone listening, and we're now going to open it up for Q&A. Operator?

[Operator Instructions] Your first question is from the line of Ken Cacciatore from Cowen & Company.

Congratulations team. It's great to see the data. Dr. Regillo, you touched on it. I'd love to hear both your -- again and maybe a little bit more detail and Dr. Duker, if you wanted to weigh in. Just that comparison, you touched on faricimab, but maybe the other long-acting VEGF and other long-acting TKIs, if you could put it into perspective, understanding it's really early data. And then also, wondering if you could just talk about the type of patient you could see with this type of results, assuming that this -- these types of results where we concluded, obviously, we don't have the full data set yet, but as we run through Phase II and Phase III, if this, generally speaking, holds up. Can you just talk about the type of patient that might be able to benefit from a different approach? And then I'd just say lastly, you did touch upon the more disease burden patients. They did have a reduction in treatment, even though, they were more disease burdened. It would seem as if to a layman that those might -- if they're not responding well to a VEGF, maybe putting an underlying TKI in and rescuing with a VEGF even makes potentially even more sense. So as I look at the data, that looks interesting. But I'll leave it there and let you respond.

Sure. A lot of questions there. I make sure I remember the first one. Oh, yes, the comparison. I think all the TKI programs are showing a biologic effect. There's no doubt about it. And as I use the word validation, this program in complete probably has the best data set, very strong, I think, overall. And the nice thing about it is, it's pretty clear that a solid sustained delivery platform that's injectable is preferable to suspension. Suspension, you got to expect some degree of dispersion. So unless keen on that approach, especially intravitreal. And we've seen issues with that. And that can obscure vision, cause inflammation. We're not seeing any of that, of course. And that's great. Plus we're dealing with a platform that's already commercially available. And so we know it has a good established safety profile, and it's nicely biodegradable. I agree, you made some great points, especially in the high need patients, that those patients are still benefiting. And Jay made reference to that, too, because it still reduced the treatment burden, and that's what patients want, and that's what we want. Patients don't want to get injections. They don't want to come to the office and get injections as frequently as we have to do right now in practice. And I think this type of approach applies to many of our existing patients. I'm convinced the majority really. And there's -- from a sustained release standpoint, the data for executive control is fantastic with something like port delivery. Again, I've had a lot of experience with that. But of course, we just heard it actually in a nice discussion section at the Academy that, many doctors are going to be reluctant to embrace that or utilize it frequently just because it's a device, it's a surgery. And it has unique adverse events, and we tend to be a little gun-shy there. And so that's going to be utilized going forward probably in a very limited number of patients. It is what it is. But this data set looks very similar to also the encouraging gene therapy. If you notice, when you look at the swimmers lane plot with what you're seeing out of both gene therapy programs with wet AMD, you'll get a few that just breakthrough that still need frequent injections inevitably. That's the case. And that's what I was made reference to, that you're always going to get a few of those. But gene therapy has unique issues, although, again, it looks promising. Here, this is titratable, and that makes us -- it's very comfortable in the hands of us the treating physicians to have something we can titrate, turn off and so forth. Gene therapy has a long way to go, of course. But I think as a TKI platform, this is looking really good.

And I just -- I hope to be able to answer your third question, if I can remember, Ken, it was about perhaps how -- which kind of patients might benefit. So I think we're looking at this in 2 ways. The first way is, the most immediate, which is we want to get this FDA-approved as expeditiously as possible. Once it's FDA approved, we hope, then I think the repo community is going to figure it out, and Carl can certainly chime in when I'm finished with this. But here's the way I think it's going to work. I think we're going to have identified a significant proportion of the population that will do well with EYP-1901. Doctors will try it, but they'll see the patient at the beginning frequently and see how they do. And let's suppose we have a label for 6 months hypothetically, and they do well at 6 months, they'll just keep injecting every 6 months. That will be some segment of the population. There might be a patient who you inject them with EYP-1901 and they are fluid in a month or 2. And I think that doctor will need you to decide to do a combo therapy, perhaps, like what I showed you with the second case or just say it's not working, I'm to go back to standard of care, and there's nothing wrong with that either. And I think you'll have a third population who are clearly getting a reduced treatment burden with EYP-1901 which is -- they're not needing the injection every 4 weeks, 5 weeks, 6 weeks. They can go every 3 or 4 months down the lane. And even though for those patients, they may not make it out as our label suggests, I think that they will still benefit from that type of treatment. So again, this is hypothetical, and I'm happy to see if Carl might agree is that how the retina community might approach this?

Yes, I agree. And I think we're dealing with 2 types of treatment, if you will, sequential therapy, meaning you start with standard intravitreal injections of one of our anti-VEGF biologics. And then you go on to a sustained release platform here with TKI. And therefore, you get this good disease control with that mode of action or add-on or supplemental therapy. And that's the analogy there is actually what we do sometimes with our DME patients that have high need for or inadequate response to anti-VEGF will add a similarly long-acting steroid, such as OZURDEX. And that often allows us to back off, and you mentioned it, back off on our decrease the frequency of the anti-VEGF, and patients, of course, benefit from that disease -- not just disease burden, meaning frequency of office visits and injections, but potentially better long-term vision outcomes.

Next question operator?

Your next question is from Yatin Suneja of Guggenheim Partners.

And let me congratulate you all as well, very good results. Just a couple for me. So first is on the 3 patients that were rescued in month 1. Can you maybe just talk about what are potential strategies to maybe screen them out in future studies? And then with regard to the 8 out of 17 patients that did not require any rescue, like what were the defining characteristics? Are there -- or is there a strategy where you can leverage either OCT biomarker or something in your enrollment criteria moving forward in Phase III to sort of get that type of patient population? And then I have 2 more.

Okay. Well, we'll get back to it. Thank you very much for excellent questions. And I'm going to answer the second one first, because the answer is, this is a direction that we're going, but it's far too early for us to know this. We need to really get close look at the OCT data and coordinate with our reading center. I think I'm going to let you know that we've got aqueous Humor data also for Vorolanib levels. We are -- it's far too early to try to correlate that to response. So we've got a lot of work to do, and we're prepared to do it. To answer that second question, which is -- which eyes do best. The way you screen them out though, other trials have done this prior, and there's a couple of different strategies we can use, and we're contemplating any of them. And I think, again, the overriding goal here is to get FDA approval as quickly as possible with as broad label as possible. So keep that in mind with my answer. So one of the things we could clearly do that could have not enrolled those 3 bad eyes, if we'd like to call them, is we could have a run into the trial, a lead-in. In other words, the investigator would do a standard of care injection and do an OCT. See the patient back a month later. If the OCT a month later meets rescue criteria for that study don't enroll them. And the ones who don't meet respiratory enroll. That would have been a simple way that probably could screen out those patients. We could do other things like ad screening, look at OCT characteristics like intraretinal fluid or degree of subretinal fluid or size of the [indiscernible] detachment, size to the corneal vascularization. There's just a lot of things that we are really excited to look at to try to get that data. But we don't really know what the answer is yet. But overriding, we're going to make it as simple as possible, as broad as possible, but we do want to try to identify what we hope is the large subpopulation of what MDIs that do well with us.

Jay, I think you'd also mentioned about the paradigm-shifting potential. So can you just talk about what does it mean from a patient perspective from treatment burden? Obviously, the slide that you have up right now, pretty powerful. Clearly, we can see in the yellow box to the left side, right? What does it mean for off it visit requirement and how you might employ a PRN dosing strategy using this drug in your practice?

Yes. So it's, again, without the exact data to inform the retina specialists on how many patients can go 6 months, 9 months, 4 months, et cetera. We don't know that exactly. It's going to be hard to give that type of direction. And the other thing we hope to inform the retina community is what are the parameters that allow a patient to go that long. It does appear -- the patient I showed you, the first patient that entered dry and stayed dry for 9 months. And it may be that the patients and we know from the EYLEA recent high dose EYLEA study that 50% of patients who are getting EYLEA every other month or dry. So that could be 50% or more of the population are dry, and they may do very well. But I think the retina community is one that because we all have our own OCTs, we like to individualize therapy for patients. And that's why I mentioned this already. I think we're going to -- if the FDA approve, the retina community will figure it out. But I also think there's going to be a benefit to have the peace of mind for patients and practitioners that even if the patient misses a visit, there's anti-VEGF on board. And so that type of idea that, yes, I'd like you to -- you were coming in every month. I think you should come in every 3 months now, and maybe that will be adequate. But if you miss a visit in the back of your mind, you're thinking that may be okay. I don't know, Carl, do you want to pipe in here?

Sure. When we first had the anti-VEGF biologics, we utilized more or less PRN like approach. And we then went to, what I'll call a better and validated treatment approach, which is the treating extend approach. And with short-acting biologics, the treat and extend approach works really well, because you can fine-tune individual patients' needs. But it's within a narrow time frame, 4 to 12 months. As we get into now therapeutics that are much more longer acting, I think you're going to see a shift back to PRN, because we want to more precisely pinpoint when the patient is going to need treatment. And it's going to dovetail perfectly timing-wise with home OCT, which is on the very near horizon. So I think regardless of the approach, port delivery, these TKI delivery systems, we're going to probably utilize that. That's what I'm predicting. And I think patients will also like that approach. It is telemedicine, in essence, to not have to come to the office, and then we have a certain trigger, certain amount of recurrent exudation that will then determine when the patient needs to come back to the office and be retreated. So I think the future is going to change substantially.

And then maybe a final question. Can you just talk a little bit about the regulatory endpoint. How the development that could look like? Is it going to be a non-inferior and how the treatment burden -- reduction in treatment burden can get incorporated in those endpoints?

Yes. Let me just comment on that, that right now, it's too early, and we're still finalizing our plan. So we'll certainly inform everybody once we lock down our Phase II study designs.

Your next question is from Jennifer Kim of Cantor Fitzgerald.

Congrats team on just some impressively clean clear data. I have a few questions here. Do you happen to have data on hand on what the average BCVA change and OCT change were in patients who didn't require rescue at 6 months and what that looks like at month 6?

We haven't. It wasn't part of this presentation. We have, again, 2 parts to this answer, Jennifer, and thank you for the question. We have a lot of data that we just didn't have time to share, but some of it still isn't finalized data. And so some of it, we haven't had a chance to really analyze. Remember, the last 6 month patient visit was only a few days ago. So we do expect to be able to share that in the future, but it's not in a format that we could be comfortable saying this is what those unrescued patients definitely will look like from visual acute OCT perspective.

Okay. That makes sense. And then for -- maybe for Carl and Jay, in the post hoc analysis of the patients without IRF, I was just curious how common is -- in real life, how common is the incidence of IRF at baseline? And then how big is that population?

Well, again, intraretinal fluid in a patient who just had an anti-VEGF standard of care 5 weeks prior, and has been previously treated, I don't think it's common. We had 4 out of 17, almost 20%, 25%. I think the number is the real works less. Carl, what do you think?

Yes. After the induction phase, you have approximately -- I know this has been established with aflibercept, up north of 70% of patients are drawn, say, dry or nearly dry a month after the third dose. And so in many of those patients, of course, can be extended beyond that. When you look at the treatment extend data and you look at the distribution of disease-free interval in treatment, up 25% of patients are being dosed every 4 weeks, but many of those are dry. They're not necessarily wet, they just need to be delivered treatment frequently to stay dry. And of course, by definition, anyone that's extended longer is going to be dry. And so the majority of our patients are really good responders with the current anti-VEGFs and the ones on the horizon, and they look to be about the same, drying effects and so forth.

And my last question is, I know it's early to talk about the next steps. But heading into the Type C meeting, can you maybe lay out the key questions you have and the guidance -- the specific guidance you want heading into the pivotal. I know you've talked before about different potential pathways. You can take 2 expedite development. What are the ones that are sort of under consideration as you look at the data today?

Yes, Jennifer, thanks for the question. Until we actually meet with the FDA and get some of these answers, I think that it's too premature to discuss it. But the purpose of this is we are thinking forward, we are not thinking just about the next study. We're thinking about the pivotal. We're thinking about label, we're thinking about how it's going to get used in the real world. And so we'd like, if we can, to design a wet AMD Phase II trial that resembles the pivotal trials as closely as possible. And in order to know that, we got some questions for the FDA. So that's a general answer, but that's the rationale behind the meeting.

Okay. Great. That's really helpful. And congrats everyone again.

Your next question is from I-Eh Jen of Laidlaw & Company.

And my congrats to the severe outstanding outcomes. Maybe just I have 3 questions here. First one is a little bit technical in terms of the IIF screening, you mentioned the 2 possibilities. Could you sort of give us a little bit pros and cons of each of these options and maybe some more color on that?

Sure. First of all, please don't take it to mean that we're going to do IRF as a parameter that would screen out patients in our next trial. That has not been determined at all. I just wanted to show you an example of what a type screen out might look like. The issues really is when you have a lead in type thing like that, you lose patients. In other words, patients who say, yes, I'd like to be enrolled in this trial, they get a shot, they get an OCT. And then you're going to have probably more screening failures certainly than if you don't do something like that. The other option, if we're going to use OCT, and I'm not saying we definitely are to screen out certain patients is, you ask the investigator to look at the OCT themselves at screening. This is the quickest and most expeditious way to do it and make a determination that the patient is eligible or not. And obviously, that is quick, the patient's right there, if they meet the other criteria, you can enroll it in that day. But the problem is obvious, which is what an investigator says is intraretinal fluid or subretinal fluid or size of the membrane is not necessarily what a reading center will say. And so most reading centers will provide within 1 week turnaround service where you can have a screening OCT Fluoroscan color fundus photographs done, send it to the reading center within a week. They'll tell you meet screening criteria or not. So those are just 3 ways that it can be done, how we're going to do it until we've really done the analysis of the rich data set we got even from 17 patients. We got a lot of data to go through. We really can't say because we just don't know yet.

And maybe 2 more quick questions. First one is that this is interim data. So I assume there will be the final twelve month data. When you guys anticipate this could be reported? And would that be -- what type of value you are considering?

Well, thanks for the question. We are planning on giving an update to the data angiogenesis in February. And 6 months from now is May 2022. And so somewhere around that time frame, we should be able to update the final data, safety and efficacy. That has not yet been determined yet. What type of venue it will be following that May date. But certainly we will add some more data at angiogenesis in February.

Maybe my last question here is that to Dr. Regillo, that or actually to Jay as well. Do you anticipate if the data coming forward, continue to show similar patterns as we have seen today? Do you feel this should be a first-line therapy to replace the current standard of care? Or how would you see that potentially do get out in the marketplace?

Sure, yes. This is Carl. Actually, I don't think any of the sustained delivery approaches are going to be necessarily first line. That's not to say in practice, people wouldn't sometimes consider that. But in general, I think we're going to start with our current way we treat wet AMD with the anti-biologics upfront. We're just not going to have the data. There won't be any studies to look at first line. And you just might need higher levels and more frequent, more aggressive treatment at first. So that's why I wouldn't consider whether it's this approach or port delivery or gene therapy, any of these that are in the assisting release category, long action -- long-acting approaches to be utilized first line. But keep in mind, the 98% of the patients I see every week are previously treated established patients. That's -- and that's why every time we get a new and exciting treatment that looks like it adds value. We saw that going from Lucentis to EYLEA. It gets -- it's a big launch, right? It's very successful out of the gate.

But ultimately, would that be a goal potentially as the first-line existing has some experienced in the real-world and sustained what was anticipated goal?

But this may be a label issue, too. We didn't do any untreated patients in DAVIO. And so we don't have any data on that. And it's certainly possible that the company may never have data on previously untreated patients. We may see a maintenance therapy. And there's nothing wrong with that. There's nothing wrong with a patient getting 2, 3 or 4 EYLEA's every month, getting dry and then getting a sustained release treatment. That's -- might be a perfectly acceptable way to go in the future. So I don't think you should be comparing us or any true sustained release to any treatment that's getting a label for monthly. That's not what we're doing here. We're trying to reduce the visit burden and the treatment burden and possibly, we hope, of course, get better visual beauty results because we hope to have long-term anti-VEGF on board. So if patients can't make visits or miss visits, it hopefully will not affect their visual acuity as much as what's happening in the real probe right now.

Again, congrats.

Your next question is from Yi Chen of H.C. Wainwright.

Could you please comment on why the Moto's and Mito seem to appear to perform better than the high dose? And whether there are any observed differences in safety profile between doses?

Yes. So first of all, I'll remind you that the end of the study was 17. We only had 3 eyes in the low dose, one in the medium low, 8 in the medium and 5 in the high. So 1 patient in either direction can really skew things. Remember also that the 3 patients who got rescued at 1 month, 1 of them was in the low dose, 2 of them were in the high dose. So if you look at -- if you were to just take those patients out for a moment and look at the results without the 3 patients who got rescued at 1 month, the rescue free rate up to 6 months in the low dose would be 33% in the medium -- the low medium to be 100% rescue free because that patient still hasn't rescued. Medium dose would be 50% and high dose would be 60%. So that does show, again, I hate to say it with such low numbers, a bit of a dose response, a bit, but we'll certainly be looking at dose response in the future trials. The good news for us in the future trials is we had no real toxicity hearing. Certainly, no dose-limiting toxicity. So while we haven't selected the doses yet for the next trial, I think DAVIO reassures us, that if we choose to go with a high dose, it's certainly going to be a safe option.

So is DAVIO trial going to help you select the final dose or the upcoming Phase II trial will have multiple doses as well?

Well, we haven't completely decided that yet. But if I answer the question at a general level, that's typically what Phase II trials do, is give you confidence in your final doses. Remember also that this is a bit, as I've said, 3 or 4-dimensional chests, because we not only have multiple doses, we have multiple intervals. We can choose multiple intervals for reinjection of EYP-1901. And what we will do is choose the dosing level that's safest and most effective and also choose interval or intervals that give retina specialists the most flexibility. So we are looking for a flexible label. And I think you'll see that reflected no matter what we choose in the future studies. That will be one of the rationales by the dosing intervals that we select.

Let me also add that we want to be able in that design to take into account reimbursement. So that if you end up with some patients, and we -- that have to get treated with standard of care a little more frequently, that's okay. And we -- or excuse me, if we want to move it up and patient needs to get retreated more frequently. They need to know that that's going to get reimbursed, because as you can see in this study, we didn't get to 100% after 6 months. So we don't expect that patients are different, and we need to be able to have flexibility for doctors as well as for reimbursement.

Got it. And do you expect different doses might perform better for different patient -- sub-patient groups, such as those with intraretinal fluid?

Yes, it's certainly possible. And that's something when we expand the studies and get a little more experience with those OCT biomarkers coming into the study and other potential characteristics of the eyes that we're going to be able to answer that question better. We just don't know yet. And it's too small.

I am showing no further questions in the queue at this time. I would like to turn the call back to Nancy Lurker.

Yes. I just want to thank everyone for your participation on the call today. And I do want to say that looking ahead, we do plan to initiate a Phase II trial in Wet AMD in 2022. Let me just again remind you that we do have a scheduled Type C with the FDA on December 1, to discuss the details of our go-forward planning and make sure that we get guidance for our registration trials. Finally, I want to give a huge shout out to our fantastic team at EyePoint Pharmaceuticals. Thank you for all that you did to bring our Phase I study to conclusion. And I also want to especially thank the DAVIO investigators, the patients and the site personnel who participated in this study and who were vital to its success. We could not have done this without you. This concludes our program, and we look forward to future updates.

Thank you, speakers. Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.