EyePoint Pharmaceuticals, Inc.

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

Thank you, and thank you all for joining us on today's conference call to discuss iPoint's third quarter 2025 financial results in 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 door review in wet AMD and DME. I will close with commentary on the third quarter 2025 financial results. We will then open the call for your questions where we will be joined by Dr. Ramiro Ribeiro, our chief medical officer. Earlier this morning, we issued a press release detailing our financial results and recent corporate developments. A copy of this release can be found in the investor relations tab on the company website, www.ipointpharma.com. 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 Dugard, President and Chief Executive Officer of I-Point.

Thank you, George. Good morning, everyone, and thank you for joining us. I am pleased to discuss with you today the tremendous progress we've made during the past quarter, continuing our strong track record of execution. As you will hear, our momentum underscores our confidence in the differentiated clinical profile of DuraView, our lead program, and its potential to transform the treatment paradigm into two largest retinal disease markets, wet H-flated macular degeneration, or wet AMD, and diabetic macular edema, or DME. I'd like to start with a brief overview of our recent highlights. DuraView is on track to be the first to file and first to market among all current investigational sustained delivery wet AMD and DME programs, positioning DuraView at the forefront of the treatment landscape with potential first mover advantage. We completed enrollment of the Lucia trial the second phase three trial for DuraView and WET-AMD in July. Both trials, Lugano and Lucia, were enrolled in seven months and together recruited over 900 patients, making them among the fastest enrolling WET-AMD pivotal programs to date. Top line data for DuraView and WET-AMD is expected in mid-2026. Following the positive end of phase two meeting in July for DME, We were pleased to align with the FDA on a non-inferiority trial design that we believe is clinically rigorous, efficient, and de-risked. As a reminder, DuraView is the only tyrosine kinase inhibitor, or TKI, in development for DME. We are rapidly moving forward with a pivotal phase 3 DME program with first patient dosing expected in Q1 2026. The Phase III DME trials, COMO and COPRI, will leverage our existing wet AMD clinical trial infrastructure and our enthusiastic network of investigators. We announced new preclinical data showing that virolinib The active drug EnduraView is unique among TKIs being tested in retinal diseases as it inhibits both VEGF-mediated vascular permeability and interleukin-6 or IL-6-mediated inflammation. This multi-mechanism of action has the potential to be particularly effective in the treatment of multifactorial diseases such as wet AMD and DME. These new data underscore the impressive Phase II results of the Verona trial and DME, and strengthened our confidence in our clinical programs. Finally, our path to potential success in Phase III is supported by our strong balance sheet. We ended September 2025 with over $200 million in cash and equivalents, and closed a $172 million follow-on offering in October. Our cash is now expected to fund operations into Q4 2027, well beyond Phase 3 wet AMD data anticipated in 2026. With this continued exceptional track record, iPoint will enter an eventful 2026 from a position of strength. Now, I'd like to take a closer look at the current market landscape for wet AMD and DME. With a combined current global market of $10 billion and growing, these indications make up the vast majority of the global branded retinal disease market. Despite the size and scale of these diseases, they are dominated by a single treatment modality, monotherapy anti-VEGF biologics. Due to the high burden of frequent injections, many patients remain undertreated, even with the addition of recently approved extended duration options. Additionally, these current standard of care anti-VEGFs demonstrate subpar real-world efficacy in DME, with growing literature supporting the role of not only VEGF activation, but also IL-6 signaling and inflammation driving disease severities. We believe our lead product candidate, DuraView, is well-positioned to deliver much-needed innovation in both wet AMD and DME. As a differentiated, sustained-release TKI, DuraView is designed to improve the current standard of care by providing durable disease control while reducing the treatment burden. Further, DuraView's potential multi-MOA blocking VEGF, PDGF, and IL-6 signaling may be uniquely suited to effectively address multifactorial retinal diseases such as DME and wet AMD. Beyond its unique MOA, DuraView offers a compelling product profile that supports strong competitive positioning in both wet AMD and DME. Unlike other sustained release options in development, DuraView is formulated in R DuraCert E technology. a bioerodible sustained-release insert specifically designed to prevent free-floating drug particles. Additionally, DuraView is shipped and stored at ambient temperature and administered via a standard intravitreal injection. DuraView features the most robust clinical data package among all investigational sustained-release programs. This includes Phase II wet AMD and DME data, demonstrating meaningful visual and anatomic improvements from a single Duravu dose and a consistent and favorable safety and tolerability profile with no safety signals observed in over 190 patients across four completed clinical trials. Given its advantageous clinical profile, multi-target MOA, and unique storage and administration conveniences, we are confident that the review offers a differentiated value proposition that is meaningful to physicians and patients and, if approved, would present a compelling option within the current and future landscape for retinal disease treatment. Let me now walk through recent updates for our Phase III programs, beginning with wet AMD. Our fully enrolled Phase III pivotal program remains on track to deliver top line data starting in mid-2026. As a reminder, in July, we completed enrollment of the Phase III program with over 900 patients randomized across the two trials. To ensure we are positioned for commercialization, we are highly focused on our manufacturing capability and CMC submission for an NDA. We have already produced the review registration batches at our state-of-the-art GMP compliant manufacturing facility in Northbridge, Massachusetts. The 41,000 square foot facility was built to both US FDA and EMA standards and will have capacity to support the commercial launch. Moving on to the recently initiated phase three program in DME, our program consists of two non-inferiority trials, COMO and COPRI. evaluating Duravue 2.7 milligrams versus on-label Aflibercept control. Each trial will enroll approximately 240 patients. Additionally, given the established non-inferiority pathway, as well as our ability to leverage our existing Phase III clinical trial infrastructure, we believe the program is significantly de-risked. We look forward to dosing our first patient in Q1 2026. As I mentioned earlier, there is growing clinical evidence supporting the multifactorial nature of retinal vascular diseases with both VEGF-mediated vascular leakage and inflammation contributing to disease pathogenesis. IL-6, a pro-inflammatory cytokine, is a key driver of this inflammation and is found at significantly higher levels in DME and wet AMD patients versus healthy individuals. Recent preclinical findings, which we presented at the American Academy of Ophthalmology meeting in October, demonstrate that virolinib, the active ingredient in DuraView, inhibits IL-6 signaling through JAK1 receptor blockage. In addition to its known inhibition of PDGF and all VEGF receptors. In vitro data shows a meaningful reduction in IL-6 activity of more than 50% with virolinib, suggesting a multi-MOA capability. This data may explain the rapid fluid reduction in vision improvements observed as early as week four in the Duravu arms in the phase two Verona trial. In summary, We are well-positioned to extend our clinical leadership in sustained-release therapy for the two largest retinal disease markets. We remain focused on reporting top-line Phase III data for both Lugano and Lucia starting mid-next year, positioning DuraVute to be the first to file and potentially first to market among all investigational sustained-release programs in wet AMD. Our Phase III DME program is now underway, and we expect first patient dosed during the first quarter of 2026. We are moving swiftly and confidently to bring DuraView to patients in need, while continuing to ensure our progress follows a de-risked, clinically rigorous, and patient-centric approach. Before passing it over to George to review our financials, I want to thank the entire iPoint team for your dedication to improving patients' lives through better vision, as well as the patients, study coordinators, and clinical investigators outside of our organization who enable our clinical research. We are grateful for your confidence, and we are proud to advance our therapeutics for the benefit of the entire retina community. We look forward to continued progress towards our upcoming milestones as we further our leadership in sustained ocular drug delivery. I will now turn the call over to George. George?

Thank you, Jay. To begin, we continue disciplined financial management and good stewardship of our resources, ending the third quarter with $204 million in cash and investments. As Jay mentioned, in October, we completed a $150 million follow-on financing plus the exercise of the underwriter's green shoe option on October 29th for a total of approximately $172 million in gross proceeds. adding to our cash position and enabling the execution of the Phase 3 DME program. We expect that cash and investments as of September 30th, along with net proceeds of the financing, will support our operations into the fourth quarter of 2027, well beyond key data readouts from the Phase 3 Lugano and Lucia pivotal trials anticipated in mid-2026. As the results for the three months ended September 30, 2025 were included in the press release issued this morning, my comments today will be focused on a high-level review for the quarter. For the quarter ended September 30, 2025, total net revenue was $1 million compared to $10.5 million for the quarter ended September 30, 2024. This decrease was primarily driven by the recognition of deferred revenue related to the company's 2023 agreement for the license of UT product rights in the prior year period. Operating expenses for the quarter ended September 30, 2025, totaled $63 million compared to $43.3 million in the prior year period. This increase was primarily driven by clinical trial costs related to the ongoing Phase III Lugano and Lucia clinical trials of Duravue for wet AMD. Net non-operating income totaled $2.3 million, and net loss was $59.7 million, or $0.85 per share, compared to a total net loss of $29.4 million, or $0.54 per share in the prior year period. As I noted earlier, cash and investments on September 30, 2025, totaled $204 million, compared to $371 million as of December 31, 2024. which along with net proceeds from the October financing, we expect will enable operations into Q4, 2027. In conclusion, we are very pleased with our progress and continued execution in 2025 and are well capitalized to deliver DuraView phase three wet AMD data in 2026 while advancing our phase three DMV program with the Como and Capri clinical trials. I will now turn the call back over to Jay for closing remarks. Thank you, George.

As you've heard this morning, I-Point is on the cusp of a milestone year in 2026. Our decades of drug development experience, clinical track record, next-generation technology, and blockbuster potential of our Duravue franchise underscore our exciting growth story. With our strong balance sheet and disciplined cash management, along with our thoughtful de-risk development strategy, we are prepared to execute through our key upcoming milestones, including top-line data for the Phase III Lugano trial anticipated in mid-2026, with Lucia data to closely follow, positioning us for a potential NDA submission for Duravue and WET-AMD, and the first patient dosing at our pivotal Phase III DME program anticipated in Q1 2026. with full enrollment expected in the second half of 2026. Thank you all for your attention this morning. I will now turn the call over to the operator for your questions.

Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask a question, you will need to 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 during the course of the call. Please limit the number of questions you ask to one to give others a fair chance to participate. Please stand by while I compile the Q&A roster. Our first question comes from Tess Romero from JP Morgan. Please go ahead.

Thank you. Good morning, Jay and team. I wanted to ask a market-sizing question today. Can you just refresh us for the wet AMD population overall here in the U.S.? What percent of patients are treated every four weeks, every six weeks, every eight weeks, or longer? And what is your latest view on how the doctors will use DuraView if available in that context? Thanks so much.

Good morning, Tess. Thanks for the question. It is insightful, and as you may surmise, the data is not strong to give exact numbers for each of those intervals. What we do know is approximately 20% of wet AMD patients have to be treated monthly regardless of the drug that they're using. If you look at the clinical trial data, even with the newer extended duration agents, 50% of the eyes can't go longer than every eight weeks. Depending on a doctor's toleration for fluid, some patients can certainly go three and four months in between injections. But again, it's individualized to the patient. and oftentimes individualized to the doctor's tolerance of fluid and adherence to the label. So I don't, off the top of my head, have exact numbers to give you for those other percentages, and I'll pause and see if Romero has any other insight.

Romero- Yeah, no, thanks, Peter, for the question. I think when we think about do review in our Phase II data, we showed that after dosing DuraView, about 65% of patients did not require any supplemental injection with anti-DGF. And even when we look at zero or one injection over that six month period, then the number is about 90%. So we believe that DuraView is really well positioned if we see the results in the phase three study being replicated to be in the market for wet MD patients.

And to answer the second part of your question, Tess, I don't think you can look at it as an either-or, meaning if the review is approved, doctors will be limited to just using one agent. We're a different MOA, and clearly the more recent data with IL-6 inhibition suggests that we may offer an MOA that the ligand blockers cannot. That would open up market tremendously to us. And as Romero just explained, physicians, I'm sure, would be willing to take advantage of two MOAs. We do that in chronic diseases all the time. And therefore, the market share for Duravue, when you speak to some of the KOLs on the podium, even recently have said up to 80% of their patients would be eligible. So we're really optimistic that the acceptance of a multi-MOA TKI with sustained release in both wet AMD and DMV is going to be high.

Great. Thanks so much.

Thank you. Our next question comes from from Citi. Please go ahead.

Thanks for taking our question. Regarding DME, can you provide any additional color on how you're structuring your enrollment criteria to provide the broadest reach in the DME marketplace for autistic competitors in the long-acting TTI space?

Thanks. Sure. I'll let Romero answer that question. Thank you very much for it. And again, I can quickly answer the second part of the question. we're the only TKI sustained release that has a DME program. So that part's easy. But Romero, why don't you talk a little bit about how we've designed the trial?

Yeah. So first, you can have an overview on our phase three DME program, COBRA and CAPRI. So we are going to be enrolling patients with active DME, both treatment naive and previously treated. As a control arm, we're going to use a Flibercept on label. and then do review is going to be being those every six months. We are very fortunate to have a strong infrastructure here at iPoint. As we conducted our wet in this study, we have also a very strong relationship with investigators. So for our DME program, we're going to be able to leverage those strengths into a hopefully rapid enrollment for the DME program. I think it's our understanding that We might be the only phase three program enrolling patients next year for this indication. So, again, I think we expect to see a rapid enrollment, similar strength as we did for the web enrollment program.

And regarding enrollment, just for clarification, I believe I heard you say second half 26. Is that for both Como and Capri?

So I think what we're guiding now is that both studies are going to be starting Q1 of next year, 2026. Got it.

Thank you so much.

Appreciate it.

Thank you. Our next question comes from Tyler Van Buren from TD Cowan. Please go ahead.

Hi, this is Sam on for Tyler. Thanks for taking our question. I wanted to ask about the use of the blended endpoint, which you guys have remained consistent on with the pivotal wet AMD and DME trials. We've seen the FDA green light a single endpoint more recently, so curious if you thought about using a single endpoint at all for the DME studies and why you believe the blended endpoint is the best approach. Thanks.

Thanks, Sam. Appreciate the question. And I'll let Romero go into the details, but to answer quite simply, did you think about a single endpoint? Quick answer is no. Romero, why don't you talk a little bit about our interactions with the FDA over endpoint and why the blended endpoint is actually de-risking?

Yeah, and thanks, Sam, for the question. So for both our WET-MD program and our DME program, we are using blended endpoint, meaning that For the primary endpoint, we're counting two visits. The benefit of that is that we prevent missing data. So in this type of study, it's not uncommon to see patients missing the visit because they have medical appointments or they're in the hospital for some systemic disease. So by having two visits, we reduce the amount of missing data. And also very important, if a patient has for any reason a loss in vision in one of the visits, it has the ability to capture the recovery of that vision in the next visit. The use of blended endpoint has been common in clinical trials for retina disease for the past few years. with the main goal of decreasing the variability and increasing the power of the study. And that's why we feel confident on using the blended endpoint for both wet and DME. And of course, we have the green light from the FDA to do so.

Great. Thank you for that clarification. Really appreciate it.

Thank you. Our next question comes from Clara Dong from Jeffries. Please go ahead.

Hi, good morning. Thanks for taking our questions. This is Jenna for Clara. Could you talk about the differentiation in IL-6 inhibition? And could you help us kind of elaborate on how that could translate into clinical benefit in DME versus an anti-VEGF only approach? Thank you.

Thanks for the question, Jenna. And this is really timely because you may be aware there's some recent data from Genentech who used an IL-6 blocker in a DME trial combined with an anti-VEGF. Both were delivered monthly, and the arm with the IL-6 blocker along with the anti-VEGF had better vision as early as week four and sustained through the trial. We were able to show a very similar vision improvement and course of improvement in our Verona trial using just two injections over six months as opposed to 12 injections over six months. And when we looked into it more closely, we discovered that, in fact, Virolinib is a potent inhibitor of IL-6 pathway by blocking the JAK1 receptor. There is substantial evidence in both wet AMD and DME that IL-6 plays a pathogenic role, especially in eyes that are not responding. And therefore, the ability to block both VEGF pathway and inflammatory IL-6 pathway could be a significant improvement over what we have now especially coupled with sustained release so that you're not having to give two biologics on a monthly basis.

Thank you. Okay, thank you.

That's wonderful. Our next question comes from Yatin Sunaja from Guggenheim. Please go ahead.

Hey guys, thank you for taking my question. Maybe two questions for me. One is on the mechanism regarding the IL-6. Jay, if you can comment on, you know, the relevance of it in one disease versus the other, do you think there is more relevance in DME versus AMD? So that's one. And then the second question is, you know, now more around the expectation now that the studies, wet AMD expectations, right? Now the studies are enrolled. I think our investors are sort of beginning to think about what we should be expecting from the data. And I think there is focus on three things. One is the, you know, BCV and on inferiority, what sort of injection burden you can produce and how should we think about rescue rate. So if you can comment on that, that would be very helpful. Thank you.

Thanks, Yatin. Two great questions. Let me start with the aisle six question. IL-6 has been implicated in inflammatory macular edema for well over a decade. And additional data suggests that IL-6 levels in the vitreous are much higher in DME patients than in diabetics with no diabetic retinopathy. In addition, there's data that suggests high IL-6 levels in aqueous humor portend a worse outcome in both DME and wet AMD. So overall, the evidence for a role of IL-6 as an inflammatory pathway in DME is very strong. And while it's there in wet AMD as well, it appears to be a prognostic factor in the percentage of eyes that aren't doing well with VEGF blockage alone. We believe that if the preclinical data we have shown And the rapid and early and sustained response in our Verona DMV trial can be shown in phase three. This would be an exceptional result, which would put us at the forefront of both wet AMD and DMV therapies. As for the clinical trial results, which we expect, again, the first trial, Lugano, mid next year, second trial, Lucia, soon to follow. Based on our strong phase two data, we would expect non-inferiority to the on-label ILEA control with continued safety. And again, safety is of paramount importance here, as I'm sure you all know. But based on the ongoing mask safety that we've seen in these two phase three trials, as well as the extensive safety database we have for both Duravue and Virolinib, we're confident that the safety will be quite good. As for reduction in treatment burden, again, that's important. There's no specific cutoff that says it has to be above or below a certain level. And based on our discussions with KOLs and the design of the trials, we think a 50% reduction in treatment burden will, again, put us into the forefront of therapies for wet AMD.

Thank you.

Our next question comes from Deepajana Chatterjee from Jones. Please go ahead.

Hi. Thanks for taking my question, and congrats on all the progress. So assuming Lugano and Lucia meet their non-inferiority endpoints, Does your statistical analysis plan allow for testing superiority? And if so, how do you expect clinicians to interpret those data related to on-label ILEA compared to potential competitors pursuing superiority claims based on less frequent dosing?

So, Romero, why don't you answer that? Thanks, Jeff John. I appreciate the question.

Yeah, thanks for the great question. So, as you mentioned, our analysis plan does allow for testing superiority, again, the Flibercept, if our non-inferiority is met. So it's a hierarchical test. So we have the ability to test for that. Of course, if we see that Duravu produce superior visual outcomes compared to on-label Flibercept, then of course, I think would be an outstanding results for the retina community and wet MD patients and would allow us to position to review as a premium medication. Of course, having a superiority claim against own label of Flibercept, I think from a retina specialty perspective is much more relevant than having a superiority versus a single dose of a Flibercept. So we are, you know, we continue to be optimistic with our Lugano-Uchi study. We were very fortunate to have the W2, our Phase II study, to support the design of the Phase III programs. A lot of the learning is coming from there, and we're looking forward to see the results meet next year.

Very helpful. Thank you.

Thank you. This concludes the question and answer session. I will now turn it over to Jay Duker for closing remarks. Thanks very much.

Before we close, I do want to mention a tremendous honor that iPoint received this week. We were voted a 2026 Best Places to Work by Biospace. In fact, we were in the top five best biotech companies nationally. This is a testament to the incredible team and culture we built here at iPoint. Exceptional execution does not come in a vacuum. I want to thank all of our amazing team for this honor, but especially our human resources group led by our chief people officer, Jen Leonard. Thank you all for your time and attention this morning.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.