EyePoint, Inc.

Good morning. My name is Michelle and I'll be your conference operator today. At this time, I would like to welcome everyone to the iPoint fourth quarter 2025 financial results and recent corporate development conference call. There will be a question and answer session to follow at the completion of the prepared remarks. Please be advised that today's conference is being recorded at the company's request. I would now like to turn the call over to Greg Elston, Executive Vice President and Chief Financial Officer of iPoint. Sir, please go ahead.

Thank you, and thank you all for joining us on today's conference call to discuss iPoint's fourth quarter and full year 2025 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer of iPoint. Jay will begin with a review of recent corporate updates and discuss our clinical programs for DuraView and wet AMD and DME. I will close with commentary on the fourth quarter and full year 2025 financial results. We will then open the call for your questions where we will be joined by Dr. Romero-Ribero, our chief medical officer, and Mike Campbell, our new chief commercial officer. Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of the release can be found in the investor relations tab on the company website www.ipoint.bio. 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 timelines, 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 on file with the SEC, and in other filings that we have made or 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 Dr. Jay Duker, President and Chief Executive Officer of I-Point. Thank you, George.

Good morning, everyone, and thank you for joining us. 2025 was defined by significant progress and achievement for iPoint as we made important advances that set the stage for success and potential value creation for the year ahead. As a result of our exceptional clinical execution, driven by our de-risked and patient-centric programs, our lead asset, DuraView, is on track to deliver top-line data in wet H-related macular degeneration, or wet AMD, beginning in mid-2026. In parallel, we advanced to review as the only tyrosine kinase inhibitor, or TKI program, in diabetic macular edema, or DME. We are pleased to report that as of last week, the first patients were dosed in both pivotal phase three DME trials. With a strong cash position that is expected to fund operations into the fourth quarter of 2027, and multiple inflection points on the near-term horizon, we are entering a transformative period for iPoint with significant momentum. Our conviction in DuraView's blockbuster potential is underpinned first and foremost by its compelling clinical profile. In our phase two trials in the largest retinal disease markets, a single dose of DuraView demonstrated durable efficacy with improved vision and tight anatomical control. Importantly, DuraView has a favorable safety profile with no safety signals in over 190 patients across four completed clinical trials. The safety trial so far remains consistent, in the ongoing phase three Lugano and Lucia trials for wet AMD based on continued masked internal safety review and two interim reviews conducted by the independent data safety monitoring committee. In addition to its robust clinical profile, we continue to believe that the potential for every six month dosing via standard in-office intravitreal injection, a best in class delivery technology and a novel multi-MOA that inhibits VEGF, PDGF, and IL-6 via the JAK1 receptor with no TIE2 inhibition are the key drivers of its differentiated profile. This unique profile positions Duravue to address both VEGF-mediated vascular leakage and IL-6-mediated inflammation that contribute to disease pathogenesis in wet AMD and DME, thereby potentially enabling improved long-term outcomes for patients with fewer injections. Our confidence is also grounded in our established and clinically rigorous approach throughout DuraView's development. Our Phase III wet AMD program was intentionally designed to inform real-world practice and generate meaningful data for the retinal community by comparing DuraView to on-label of Flibrosept as the control. Additionally, we will be evaluating statistical superiority in treatment burden reduction and six-month redosing to support a compelling and relevant label. Based on the success of our large Phase II W02 trial and with our proven regulatory pathway and strong execution to date, we believe our WET-AMD program is uniquely de-risked and optimized to support success. We look forward to reporting top-line data beginning in mid-2026. The clinical and regulatory rigor that defines our approach also extends beyond WET-AMD, as we work to position DuraView for multiple indications. We are pleased that randomization is now underway for both COMO and COPRI, our two pivotal phase three trials in DME, where we expect to drive rapid enrollment by leveraging our pre-existing clinical trial infrastructure and investigator network. In line with our WET-AMD program, our DME program follows an established non-inferiority design, with an on-label standard of care control and redosing every six months. It was similarly informed by impressive Phase II data from the Verona trial, where eyes treated with DuraView demonstrated meaningful visual and anatomic improvements as early as four weeks. We anticipate top-line data in the second half of 2027. and look forward to building upon our strong track record of clinical execution as we advance DuraView through our Phase III DME program. We believe that DuraView is well positioned to be the first to market among all current investigational sustained release programs in both wet AMD and DME with a potential best-in-class profile. And we remain focused on building DuraView into a durable franchise targeting the largest retinal disease markets. With a combined current global market of $10 billion and growing, wet AMD and DME make up the vast majority of the global branded retinal disease market. Duravu's unique MOA, robust clinical data package, proven release technology, and attractive storage and administration benefits offer a compelling value proposition that we believe will address the longstanding need for innovation and support strong commercial positioning. As part of our ongoing commercial readiness efforts, we are thrilled to welcome Michael Campbell as our new chief commercial officer. Mike is a seasoned commercial leader with a proven track record of successful product launches and oversight of prominent ophthalmology franchises, including Lucentis and Zydra. As we prepare to deliver on iPoint's next milestones, including potential approval and transformation into a fully integrated commercial organization, Michael's deep commercial expertise will be instrumental as we position to review for a successful US launch. In addition to strengthening our commercial leadership, we continue to expand operations at our 41,000 square foot CGMP manufacturing facility in Northbridge, Massachusetts. The facility has been online for over a year, supported by about 60 full-time employees, and continues to not only support the CMC submission for our planned new drug application, or NDA, but also commercial supply. As we near regulatory submission, we are preparing for pre-approval inspection, underscoring our growing independent commercial readiness and commitment to ensuring that we are well equipped to deliver DuraView to patients if approved. Before passing it over to George to review our financials, I'd like to thank the entire I-Point team for your continued dedication to improving vision and patient outcomes. We are proud to advance our therapeutics for the benefit of the entire retina community and grateful to the patients, study coordinators, and clinical investigators who make our research possible. As we look ahead, we are excited about the upcoming milestones and the opportunities in store for us to extend our leadership in sustained ocular drug delivery. I will now turn the call over to George.

Thank you, Jay. We ended 2025 with a strong balance sheet of $306 million in cash and investments driven by continued stewardship of our resources and $173 million follow-on financing in October. As the financial results for the three months and full year ended December 31st, 2025 were included in the press release this morning, my comments today will be focused on a high-level review of the quarter. For the quarter ended December 31st, 2025, total net revenue was $0.6 million compared to $11.6 million for the quarter ended December 31st, 2024. The decrease was primarily driven by the recognition of remaining deferred revenue related to the company's agreement for the license of Utique product rights in the second quarter of 2023. Operating expenses for the quarter ended December 31st, 2025 totaled $71 million compared to $57 million in the prior year period. This increase was primarily driven by the ongoing Phase III trials for DuraView and WED-AMD and DME. Net non-operating income totaled $3 million, and net loss was approximately $68 million, or $0.81 per share, compared to a net loss of $41 million, or $0.64 per share, for the prior year period. Turning to the full year ended December 31st, 2025, total net revenue was 31 million compared to 43 million for the year ended December 31st, 2024. The decrease was primarily driven by the recognition of remaining deferred revenue related to the company's agreement for the license of UTIC product rights in the second quarter of 2023. Operating expenses for the full year ended December 31st, 2025 It totaled $275 million versus $189 million in the prior year period. This increase was primarily driven by the ongoing Phase III trials for DuraView and wet AMD and DME. Net non-operating income totaled $12 million and net loss was $232 million or $3.17 per share compared to a net loss of $131 million or $2.32 per share for the prior year period. Cash and investments on December 31st, 2025 totaled $306 million compared to $371 million as of December 31st, 2024. We expect the cash and investments on December 31st, 2025 will enable us to fund operations into the fourth quarter of 2027, well beyond key milestones and NDA preparation for the phase three wet AMD program in 2026 and fully funding the Phase III Pivotal DME Program. In conclusion, we are incredibly pleased with I-Point's progress in 2025 and are well capitalized to continue advancing Duravue through both of our late stage development programs. I will now turn the call back over to Jay for closing remarks.

Thank you, George. I-Point's progress in 2025 reflects the strength of our programs and our consistent execution. As we prepare to drive value through transformative catalysts in 2026, we will continue to be guided by our de-risked, clinically rigorous, and patient-centric approach. We are well-positioned to deliver on our near-term priorities, including reporting top-line data for the Phase III Lugano trial anticipated in mid-2026, with LUCEA data to closely follow, completing enrollment in our Pivotal Phase III DME program in the second half of 2026, and preparing for regulatory filing in WET-AMD, assuming positive Phase III data. Thank you all for your attention this morning. I'll now turn the call over to the operator for questions.

Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. As usual, we'll try to get to as many questions as we can through the course of the call. Please limit the number of questions you ask to one to give others a fair chance to participate. One moment while we compile our Q&A roster. Our first question is gonna come from the line of Tess Romero with JP Morgan. Your line is open, please go ahead.

Good morning, guys. Thanks so much for taking the question.

Good morning, Tess.

So, Jay, George, can you clarify the rate of ocular AEs that you have seen across your cumulative safety database with DuraView, in particular around the incidence of vitreous floaters and cataracts? And then, relatedly, what specifically has the physician's feedback been around your safety profile? Thank you.

Sure, Tess, happy to address that. As you probably recall, we've treated over 190 patients in completed trials. That's one phase one and three phase two trials. And the number of cataracts that were measured by the investigators in those 191 patients is 5.8%. In contrast, if you just look at the W2 data, The cataracts in the DAVIO2 study in the study arms was approximately 8%. In the ILEA control arm, it was numerically higher. It was 9%. So this is an elderly population. You do expect cataracts. But of course, in the controlled DAVIO2 trial, there was no mismatch between the cataracts at all. With respect to vitreous floaters, once again, in the entire population, 5.2% of the DuraView patients reported floaters, which is, again, consistent with what you might see in any type of study that has injections into the eye. So I think to answer the second part of the question, which is how do the clinicians perceive it, I think one of the main reasons that we were able to enroll the wet MD trials so rapidly is the doctors had really good phase two data to evaluate both the efficacy and the safety of our drug. And I think that gave them great confidence in enrolling patients. I think, again, I'd like to make one more note on safety and efficacy. We think of visual acuity as the primary efficacy endpoint, which it is for all of these studies. But visual acuity also is a safety outcome. And again, just to remind the listeners, in the W02 trial, our treated patients in wet AMD gained vision. And in fact, in the unsupplemented eyes in W02, the treatment arms gained 2.1 letters over the course of the trial, which is actually numerically greater than the ilea arm gained. The ilea arm, again, at that point was getting three injections over that timeframe because it was on label ilea. So that to summarize, We're very comfortable with our safety. We've had no ocular or systemic SAEs attributed to our drug. And in those four prior trials, no safety signals.

Thank you. Thank you. And one moment for our next question. Our next question comes from the line of Yatin Uciha with Guggenheim. Your line is open. Please go ahead.

Hey, guys, thank you for all the details. Just a quick one on the regulatory front. Just love to hear from you. How are you thinking about recent sort of FDA chatter around single study driven regulatory approvals? Does that change your strategy? Is this curious? What is possible? And then, Jay, I appreciate your comment on the safety. Clearly, it has been pretty good across phase two studies and also phase three blinded review that you have provided. Anything on opacity that you can comment? Like, how are those numbers relative to what we see with other TKIs in development? Thank you.

Thanks for the question, Jordan. So for the first question, the regulatory front, yeah, I think in general we would all welcome a more rapid and less expensive pathway to drug approvals. But as you heard this morning, and as I think most listeners know, we have two identical Phase III wet amputee trials underway that are reading out this year. In fact, the FDA would allow us to file with a single trial. Our second trial is only two months behind. And so overall, I don't know that that would give us any particular advantage in the single trial. In DME, we have two simultaneous trials that we expect to read out in the fourth quarter of 2027. And given that other regulatory agencies around the world are probably still not aligned with single trial, we don't believe we have any reason to alter our approach for these two indications. Future indications, of course, we will discuss with the agency. With respect to single trial in retina studies, I think that it's certainly something the agency may be considering in the future. Of course, there are rules around single trial filing that the FDA updated in 2023. Those rules are already out there. And in order to do that, you not only need to have a large trial, but you need confirmatory evidence that your drug is active if it's single trial. Of course, in the case of rare diseases, there are exceptions that are made. But wet AMD DME, unfortunately, are not rare diseases. So with regard to the regulatory pathway, we think our pathway is de-risked. We have taken the non-inferiority approach, which is the approach essentially five of the last approvals have taken. And we've got two trials in each of those large indications already in motion. With respect back to safety for a second, opacity is a sign that the masked investigator can see when they look into an eye. They see if there's a blockage in their ability to look into the eye, either in the back of the eye and the vitreous or in the front of the eye and the interchamber. In our W02 trial, we had about a 1% rate of vitreous opacity. We had no rates of anterior chamber opacity. That has not been seen at all with DuraView in any of the treated eyes, and we wouldn't have expected it. DuraView is designed to hold the drug until the drug is fully eluted, so we have no free-floating drug particles. We've not seen any migration of the inserts. The inserts so far at least, have not been reported in humans to break up into pieces. They just slowly buy a road and release their payload, which, again, I'd like to remind everybody, our scientists have been able to upgrade the inserts so that they're 94% payload. They're only 6% matrix. So we haven't seen any antigen opacity, and we wouldn't expect to. And the vitreous opacity percentage is low.

Thank you, and one moment for our next question.

Our next question comes from the line of Yigal Notramovitz with Citigroup. Your line is open, please go ahead.

Yeah, hi, Jay and team, thank you. I'm just curious with regard to the conduct of the wet AMD trials before they read out this summer and into the early fall. Will there be additional looks at mask safety? What will the cadence of those be and will you be reporting that to us as you proceed. Thank you.

Thanks, you all. We've got Romero on the line, our CMO. So, Romero, feel free to answer that question about continued safety looks in the WID-Indy trials.

Hey, Carl. Good to hear from you. So we have as a safety monitoring body for the studies, both internal mask review that we do as ongoing basis, as well as the independent data monitoring committee that reviews the unmasked data. The last DMC meeting was in November. At that point, they review the data from patients. And I remind you that at that point, we had over 25% of patients getting the second dose. The safety profile of the review so far has been consistent with our previous experience in the phase one, phase two studies, with nothing new to be aware. Our next DMC meeting is scheduled in May, so that's going to be the next opportunity for that group of physicians to review the L-mask data and provide updates to us.

Okay, thank you. And just one question on biomarkers. I know you identified IL-6 recently. I'm just wondering what additional biomarker work may you be doing to further explore the activity profile of RONIB?

Yigal, thanks for that question. Additional biomarker work around the JAK1 receptor and its ability to block downstream effects of IL-6. We will have additional data on that. that we're presenting at ARVO in May. We have additional ongoing studies to really try to assess the impact of that in humans. With respect to the rest of the potential receptors, we did a very extensive evaluation of the kinome last summer at the time that we discovered that virolinib was a potent inhibitor of JAK1 with an IC50 of about 80 NM And we didn't discover at the time any other significant receptors involved in retinal disease, either positively or negatively, that Virolinib was active against. Got it.

Thank you.

Thank you. And one moment for our next question. Our next question will come from the line of Clara Dong with Jefferies. Your line is open. Please go ahead.

Hi, good morning, guys. Thanks for taking my question. So just in terms of the DERIVOS MLT magnetic profile beyond the VADGF inhibition, so how prominently do you expect this magnetic differentiation to really be featured in your regulatory discussions and maybe eventual commercial messaging as well? And is there any plan for you to report more preclinical evidence of the IL-6 inhibition MOA in the future? Thank you.

Yeah, Clara, great question. Thanks for it. And a bit complicated because, you know, the story, I think, is still unfolding. Ultimately, what we all want is better visual acuity. Our patients, certainly, and the physicians who treat them. And so the great thing about what we do is eventually it's all about the data. And what we hope to show, and really, if we can show it, I think, primarily in our DME trials, is that that additional IL-6 blockage does give a more rapid onset of visual acuity improvement. That's what we showed in the Verona data. If you recall, as early as week four, the treatment arms with DuraView had already separated from ILEA. We were already four to five letters better and about 40 microns drier than ILEA. And we believe most likely that's the effect of the IL-6. IL-6 has also been implicated in wet AMD. I think it may be perhaps a little more difficult to winnow out the effects of IL-6 in the wet AMD population, but I certainly wouldn't rule out that we might end up with better visual acuity in the wet AMD population overall. Again, I mentioned earlier with respect to subgroup analyses, the subgroup in W2 that was not rescued ended up with slightly better vision than on-label ILEA. With respect to regulatory, I'm going to let Romero take a stab at that. And with respect to commercial, Mike Campbell's here, and maybe Mike can try to take a stab at how that might affect us commercially. Romero, why don't you go ahead first?

Yeah, sure. Thanks a lot for that question. So the regulatory path that we're following with both the WET-MD and the DME studies is a non-inferiority approach. So if we show that BCVA are similar to the control arm, that, of course, might be sufficient for regulatory agents. With that, for both wet EMD and DME study, as part of our analysis plan and hierarchical testing, we are going to be testing for superiority on the CBA. And as Jay mentioned, there are a body of evidence suggesting that IO6 has a role in both DME as well as wet EMD. So we're going to be investigating that in our phase 3 clinical studies.

Thanks, Ramon. And Mike, if we're able to show this additional benefit of IL-6, can you perhaps comment on the commercial aspects of that?

Yeah, thank you, Jay. And hi, Clara. The commercial approach, specifically with visual acuity and safety, and as Jay mentioned, our unique MLA, gives us a real opportunity here with IL-6 as part of that complete package. I mean, the messaging around this and the opportunity to commercialize gives us patients and providers a real opportunity potentially to have a best-in-class, durable approach to treating wet AMD and DME. As Jay mentioned, if there's an opportunity to be able to show the benefit of IL-6 in the DME population, that has a real meaningful commercial opportunity to really separate yourself in a marketplace.

Thank you. One moment for our next question.

Our next question will come from the line of Greg Stefanovich with Mizuho. Your line is open. Please go ahead.

Good morning. Thanks for taking my question, and congrats on first dosing in your DME Phase III studies. Maybe a question for Mike as the new chief commercial officer. As you come into the company, how are you thinking about commercial prep for the potential launch of DuraView, what are the key steps that are needed at iPoint over the next 6, 12, 18 months to ensure an optimal US commercial launch, especially when you might be going head to head in the competitive landscape versus another competitor? Thanks.

Go ahead, Mike. Yeah, thank you, Greg. There is a complete go-to-market strategy and approach for sure. As we think about the opportunity here, and to your point, potentially even having a competitor in the marketplace, there's a lot of precision that goes into a go-to-market approach, especially in this specialty retina marketplace. So it's areas, for example, around not only positioning and messaging the market research, the pricing research, all of that is priority, along with patient access and services. I mean, we can have a fantastic, and we believe we will have a fantastic opportunity here, but if you can't really get good at allowing patient access through coverage and reimbursement, then it can really hinder you. And so there's a lot of effort that we're putting behind making sure we have the right rigor to come to market and make it easy for doctors to be able to use DuraView, but also easy for patients to access DuraView. And just lastly, I would also add that there's a lot of really good work that is going on and will continue to go on around coverage with the payers and good payer research that we've done.

Jay, if I could just quickly follow up here. Phase III trial designs in DME are just slightly tweaked or different from the Phase III trial designs in wet AMD. Just wondering if you could point us to reasons why they're slightly different in terms of kind of loading doses, maybe maintenance doses, just things like that.

Sure. Go ahead, Romero. Yeah, Greg, thanks for the question. So when we look at our DME study in comparison to our WAC-MD program, there are two main differences. The first one is on the control arm. For non-fiority studies, the FDA mandates that you use on-label medication. And the on-label regimen for Flibercept in DME is five loading dose, followed by every eight weeks. So that's how we're going to be dosing patients in the control arm. The other difference is that for the DME study, we are now dosing due review at day one. If you recall from the wet MD study, we actually dose due review after the three loading dose at week eight. The reason for doing what we're doing in the DME study, which is to dose at day one, is to try to replicate the findings that we had in our Phase II study. If you recall from the Phase II study, we dose patients on day one with Afibicept Plus to review compared to Afibicept alone. And then in that study, we show a greater improvement in BCVA and CST early on in the study at week four. And we believe one of the reasons could be because of the role of IL-6, JAK1 in the DME disease. So we believe that if we can replicate those findings in the phase three study, providing patients an earlier improvement in BCBA and CSD is going to be something that is going to be advantageous for our patients.

Thank you very much.

Thank you. One moment for our next question. Our next question comes from the line of Debenjana Chatterjee with Jones. Your line is open. Please go ahead.

Hi. Thanks for taking my question. One more on safety. So we saw a handful of cases of uveitis and iritis in competitive trials. Could you just tell me again about your broader clinical experience in terms of this kind of inflammatory signals, even if mild or moderate, on your review? And also, is there anything intrinsic to your insert design, injector, or the overall product profile that you believe mitigates this kind of event?

Sure, Devanjana. Thank you very much for the question. With respect to intraocular inflammation, The studies usually divide it into iritis, which is inflammation in the front of the eye, and while somewhat troublesome, not typically sight-threatening, vitreitis inflammation in the back of the eye, a little more serious, and uveitis, which usually refers to inflammation in both those cavities. We do know historically biologics can cause inflammation, and there are various rates to the biologics. When they were first out, you know, there are papers that were written that up to, you know, 10% or more of patients at certain times were getting at least mild inflammation. Obviously, inflammation is not ideal. And one of the real issues, even in mild inflammation, is the concern that it might actually be an infection, which can be much more serious. So with respect to the 191 patients that we have treated in those four studies, We had two cases of iritis, and both cases were mild, treated with topical drops, and resolved quickly without any sequelae. We had no reported cases of uveitis, no reported cases of vitritis. So the overall intraocular inflammation rate is just those two patients, about 1%. We're optimistic and confident that our drug shouldn't cause inflammation to any large degree because virolin, of course, is a small molecule. It's not a biologic. We're not gene therapy. And the matrix that we're using, that 6% matrix in the inserts, that matrix has been used in our prior FDA-approved products. And there was virtually no, very low rates of inflammation reported in those previous products. So, given that and given the safety profile we've obviously seen in humans, which I just reported, the safety we've seen in animals, intraocular inflammation is not something we're very concerned about.

Thank you. Thank you. And one moment for our next question. Our next question comes from the line of colleagues with Baird. Your line is open. Please go ahead.

Great. Good morning. Thanks for taking our questions. I know we still have a number of months still before the top line readouts of the what AMD studies, but just a clarifying question on the reduction in treatment burden, the secondary endpoint. How do you plan on measuring that? Would that include the loading doses or is that measured after the loading doses? Just curious, you know, on the math there and just what our expectations should be for reduction treatment burden. And then just an addendum to that, what would be clinically meaningful? Thank you.

Colleen, thanks for the question. First of all, the reduction in treatment burden is to be measured after the load, since all the patients in the WIT-AMD trials get loaded with three monthly injections. The treatment burden clock, so to speak, starts after that. So in the first year of the trial, The DuraView patients mandated should receive two DuraView injections. The ILEA arm, the control arm, has a mandated five injections. So if there's no supplementation in the entire study, we would expect that 60% reduction in treatment burden in the DuraView arm. can tell you that our expectations, there will be some supplementation, probably in both arms, just like there was in the W02 trial, although we do believe it's likely that there will be less supplementation in the Phase III for various reasons. But if you apply the supplementation rates that we saw in W02 to the Phase III, we would have an approximate 40% reduction in treatment burden, which is excellent. So I think from the perspective of what the doctors want to see, I think any kind of significant reduction in treatment burden will be welcome because a supplementation with a TKI in the real world is not a failure. doctors don't mind doing injections. They just want to do fewer, number one. And obviously, the more important thing is they want to get better visual acuity for their patients in the long term. So the concept of sustained release is not about reduction in treatment burden. That's a positive side effect. But what we really want to see is better vision control in the long term, and we believe we can provide that. I think some doctors may be excited about the possibility of using two MOAs, having a ligand blocker biologic and having a receptor block a TKI at the same time. And that may prove to be better for long-term visual acuity results. So this whole idea of supplementation, it has a strict definition within the trials. But in the real world, I think the doctors will approach it a little bit differently. Now, as part of the trial, I think, Romero, maybe can you comment on the superiority testing that we'll be doing about treatment burden?

Sure, Jay. So our high-echo testing, number one is going to be, as I mentioned before, the non-inferiority on BCDA. The next one is going to be superiority on treatment burden. The study... you know, of course, is well-powered for the primary endpoint and non-FER-TPCVA. For this key secondary endpoint, the treatment burden, the study is also well-powered, and we should be able to detect a difference, even if the difference is 10 percent or 7 percent.

Thank you. Great. Thanks, Mark.

One moment for our next question. Our next question will come from the line of Lisa Walter with RBC. Your line is open.

Please go ahead. Hi. Good morning, team, and thanks for taking our question, and congrats on the progress. Maybe just one on safety. Wondering how we should think about the safety profile in Lugano Lucia as it relates to Davio 2. I believe in Davio 2, the 2-milligram arm performs better on things like eye pain, cataract, and floaters versus the 3-milligram arm. But my question is, how much of the safety differences in Davio2 are due to the two arms using a different number of inserts versus a different amount of drug? And how might this impact safety in Lugano Lucia, where two inserts are being used, like the two milligram arm in Davio2, but the amount of drug is closer to the three milligrams that was used? Any color here would be helpful. Thanks.

Sure, Lisa. First of all, with respect to dosage, we have animal data that shows no maximally tolerated dose of rolinib so far. And we dosed animals with approximately 10 times higher dosing than we have ever done in a human. So we don't believe there will be any sign of virulinib toxicity at the current doses that we're using, even with reinjection. So no, I don't believe any of the AEs reported have been due to virulinib. And I'd extend that to say, you know, so far, all the TKIs that have been used for wet AMD As far as I know, there's no AEs that have been suggested to be due to the drug itself. So these drugs that the doses we're using appear to be very safe in the back of the eye. With respect to insert number, the numbers are too low to really know, and that's not something we're really essentially considering. There was a higher incidence of floaters in W2 with a three milligram three insert versus the two milligram two insert. And maybe it had to do with the number of inserts, but given that we're using two inserts in the phase threes and ongoing, it's not much of a concern. And especially because the rates were low and we had nobody report decreased vision due to the inserts. We had nobody leave the trials due to the inserts. Nobody has to have the inserts removed. So from a clinical outcomes perspective, we're really not concerned either about the number of inserts we're using or the doses of varroa that we're achieving. I think that the safety in the entire cohorts really speaks for itself.

Thank you, and one moment for our next question. Our next question will come from the line of Yeo Jin with Laid Long Co. Your line is open, please go ahead.

Good morning, and thanks for taking the questions. And I recall in the press release, you have mentioned that there's a floater and the mechanism of actions of the drug could potentially reduce that. So could you elaborate a little bit more on that?

I'm sorry, Yale, you asked about the mechanism of action reducing.

Of the drug that potentially could reduce floater or something of the nature.

No, I'm not sure I followed that, Yale. The mechanism of action of Virolinib, again, includes its anti-VEGF effect, potentially the anti-PDG effect to give a benefit to fibrosis, and potentially the anti-IL-6 effect to give a better and quicker results in visual acuity. I don't think the MOA would have any effect on patients' perception of floater. And again, given that the rate of floaters for the whole 191 patients was 5.2%, I just don't think it's a concern.

Okay, yeah, I just read it. It says to prevent the free-floating drug particles. Okay.

That's the design of the inserts. And once again, the design of the insert, as it's already stated, we design these inserts so they control drug release until the drug is gone. That's the whole purpose of a sustained release insert is to control the drug release at therapeutic levels for an extended period of time. And so we would not expect free-floating drug particles. We haven't seen free-floating drug particles in any of the animal studies. And so far, there have been no reports of free-floating drug particles in the eye. So that is more of an effect of the delivery system, not the MOA as we're all in it.

Okay, great. That's very helpful to clarify that. And maybe a quick one. How many sites for the COMO and the corporate study in total ended? Some of those are ex-U.S. versus in the U.S.

Yeah, Romero, why don't you take that question, please?

Yeah, so we have both studies are global studies, so we have sites in the U.S. as well as outside of the U.S. We are planning to have approximately 140 sites across both studies. And we are leveraging a lot of the infrastructure that we use for our YTMD program. So a lot of the sites that are part of DME, most of them were also part of our YTMD program. And which was very interesting and very encouraging for us is that all sites from the YTMD program that we invited to participate in the DME studies, they agreed to be part again of the DME program again, I think highlights the confidence of the investigators in our clinical program.

Okay, great. Thanks a lot. I very appreciate it.

Thank you, and one moment for our next question. Our next question comes from online of Daniel Gadolin with Chardon. Your line is open. Please go ahead.

Hey, good morning, and thank you for taking my question. In your conversations with KOLs, what are you seeing in terms of which patients they would initially be willing to focus on when considering Virolanib? For example, are they thinking more of stable patients versus newly diagnosed patients or patients with hyperaden? And second part is, how do you expect the steps or requirements to affect the adoption of Virolanib? Thank you.

Thanks, Daniel. First of all, with respect to patient selection, I think we're all speculating a little here because we don't have the phase three data in the label. But if one extrapolates from the phase two data, I think that at the beginning, where most doctors will try it, is there patients who are being treated more frequently than they would like? every four weeks, every six weeks, every eight weeks. I think that will be the initial adoption of it. And as doctors get comfortable with its therapeutic profile and its safety, I think it will get expanded. Now, I'll modify that a bit, which is if we can show in the clinical trials that we can deliver better vision than ILEA on label, or that we're antifibrotic, or that we have neuroprotection, other benefits that are potentially that we might see, then I think the adoption will be much broader than that. I mean, if we can show that we're anti-fibrotic, I think retinal physicians will acknowledge the fact that fibrosis in the long term is an important cause of visual loss. And if you can prevent it from happening, you will result in improved vision over the years. So I think it will start off with the eyes that likely need a lot of treatment, but it may expand well beyond that. With respect to step therapy, we wouldn't anticipate it would be an issue. First of all, again, we don't know what our label will look like, of course, but our study in wet AMD is being done with a three-injection load. So if the label contains use of DuraView after three injections of an anti-VEGF, for example, then that automatically puts us beyond the initial injections into a branded drug. I will say we are looking into the possibility of Our different MOA and our six-month efficacy, if it's there, in the IL-6 blockage, if we can show a benefit there, to be considered different than the ligand blockers, which may also be advantageous to us in the long term. But, of course, that's all dependent on the data we show in the pivotal trials.

Okay, great. Thank you.

Thank you. I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may now disconnect. Everyone have a great day.