Ocular Therapeutix, Inc Q3 FY2025 Earnings Call

Good morning, and welcome to the Ocular Therapeutix Third Quarter 2025 Earnings Conference Call. As a reminder, this conference is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutix website. I would now like to turn the call over to Ocular's Vice President of Investor Relations, Bill Slattery, Jr. Please go ahead, Mr. Slattery.

Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release and filed our quarterly report on Form 10-Q, outlining our financial results and business updates for the third quarter of 2025, along with several updates to our registrational programs for AXPAXLI, also referred to as OTX-TKI in wet AMD and non-proliferative diabetic retinopathy. Ocular's Executive Chairman, President and CEO, Dr. Pravin Dugel, will summarize recent business highlights before we move to our question-and-answer session. Joining Dr. Dugel for the Q&A portion of the call will be Donald Notman, Chief Financial Officer and Chief Operating Officer; Sanjay Nayak, Chief Strategy Officer; and Steve Meyers, Chief Commercial Officer. We refer everyone to this morning's press release and our Form 10-Q for a comprehensive update of third quarter 2025 financial and business results. During today's call, certain statements we will be making constitute forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially as a result of a variety of factors, including risks and uncertainties identified in the Risk Factors section of our annual report on Form 10-K and our other SEC filings. With that, I'd like to hand the call over to Dr. Pravin Dugel to review our recent updates.

Good morning, everyone, and thank you for joining us today. At Ocular Therapeutix, we are courageous, bold, and opportunistic. We make decisions from a position of confidence. We refuse to accept the status quo in drug development, trial design, and our approach to the retina market. Our purpose is clear: to redefine the retina experience for patients, physicians, and payers around the world. 2025 has been a transformative year for us. We've advanced two registrational studies in wet AMD, SOL-1 and SOL-R, each addressing distinct clinically relevant questions. We are excited to share that SOL-R has achieved its target randomization of 555 subjects, marking a significant milestone and showcasing strong investigator enthusiasm for AXPAXLI. In addition, we have designed a long-term extension trial, SOL-X, which aims not only to provide long-term safety data but also to support the idea that early initiation of AXPAXLI treatment may yield greater visual benefits. Importantly, we've launched our registrational HELIOS program in diabetic retinopathy, which we see as the next frontier for delivering impactful, sustainable therapies for retinal diseases. This initiative aims for a broad superiority label that includes the full spectrum of diabetic retinal disease, such as non-proliferative diabetic retinopathy and diabetic macular edema. Through two strategically designed studies, HELIOS-2 and HELIOS-3, we plan to address both populations within this unified program. If these trials succeed, we anticipate not needing further studies to market AXPAXLI for diabetic retinal diseases. At our recent Investor Day, I explained how Ocular is positioned to redefine this field through three core areas: first, with the potential for a superiority label that could distinguish AXPAXLI from other anti-VEGFs in both wet AMD and diabetic retinal disease; second, by expanding the market to capture untapped opportunities in these areas; and third, enabling immediate adoptability due to a product profile that integrates well into current retina practice. Today, I would like to elaborate on how each of these principles guides our strategy and execution, positioning Ocular to potentially lead a generational shift in retinal therapy. Let’s discuss superiority. To date, no approved therapy for wet AMD has demonstrated superiority to an anti-VEGF. Each new treatment has offered only modest improvements in durability, resulting in a market that has become increasingly commoditized, with intense pricing pressures. The advent of biosimilars has shifted the market to one defined by restrictions and discounts. We believe AXPAXLI can disrupt this cycle. SOL-1, our Phase III superiority trial in wet AMD, is progressing under a SPA agreement with the FDA and is on track for top line data in the first quarter of 2026. If successful, AXPAXLI could emerge as the first and only therapy with a superiority label compared to a standard anti-VEGF dose. This potential extends to diabetic retinopathy with the HELIOS-2 and HELIOS-3 trials. Achieving a superiority label would position us uniquely in the market. This matters because such a label not only distinguishes our product clinically but also alters market dynamics. It could shield us from pricing pressures and allow AXPAXLI to be selected first by physicians rather than being relegated to later treatment options by payers. We consider this the ultimate achievement in the retina space: superior outcomes, enhanced durability, and a pricing model that values innovation. We are proud that both SOL-1 and HELIOS-2 are anchored in superiority endpoints, reflecting serious statistical significance agreed upon by regulatory bodies, providing a pathway for claims unmatched by any other company currently. The second element of our strategy is market expansion. The global anti-VEGF market is roughly $15 billion, but this number represents only those currently treated and not those who should be. In wet AMD, up to 40% of patients stop therapy in the first year, often due to the burdens of frequent injections. In diabetic retinopathy, fewer than 1% of the 6.4 million NPDR patients in the U.S. receive treatment, despite the proven efficacy of anti-VEGF drugs. The disparity between potential and actual treatment reflects a significant opportunity in retinal medicine. Our objective with AXPAXLI is not merely to capture a portion of today’s treated population but to broaden that population by minimizing treatment burdens, enhancing adherence, and improving long-term outcomes. We aim to achieve this through three key drivers: first, durability, as AXPAXLI is designed to provide sustained VEGF suppression for up to 12 months with a single injection. This could lead to less frequent patient visits while maintaining disease control. Second, flexibility, as our dosing intervals of 6 to 12 months accommodate varied patient needs. Third, confidence, supported by data from our SOL and HELIOS programs and our FDA-aligned trial designs, may provide the evidence physicians and payers need for early consistent use. Even small improvements in adherence could lead to hundreds of thousands more patients preserving their vision and a significantly larger market opportunity than currently recognized. At our Investor Day, we demonstrated how we intend to turn the treatment discontinuation trend into a retention cycle with AXPAXLI in wet AMD. Expanding into diabetic retinal disease will amplify this market expansion further, particularly with NPDR, a condition three times more prevalent than wet AMD that has no existing standard care, along with DME. This is not just minor growth; it calls for a redefinition of the market. Our third strategic area is immediate adaptability. Conversations with retina specialists reveal a common theme: workflow is crucial. They seek innovations that enhance outcomes without disrupting practice dynamics. AXPAXLI was developed with this principle. It requires no surgery, does not entail concomitant steroids, and we believe no additional monitoring is necessary. AXPAXLI will be administered by retina specialists experienced with intravitreal injections, making the process familiar. We are conducting all our registrational trials with a prefilled injector similar to those currently used for anti-VEGF treatments. Additionally, the hydrogel formulation is intended to be fully bioresorbable, leaving no traces behind. The procedure and post-injection experience will resemble current anti-VEGF treatments, except AXPAXLI could last up to 12 months. This unique combination of innovation and ease of integration allows for fewer patient visits and longer-lasting results. Physicians benefit from potentially improved treatment while payers face reduced utilization and better long-term outcomes. AXPAXLI can help specialists serve more patients efficiently and provide enough drug coverage in case of rescheduled visits, potentially easing the burdens that lead to treatment discontinuation. Ultimately, we believe AXPAXLI can optimize and scale modern retinal practices. This outlook is also shared by significant stakeholders in patient access and value. In recent months, we have engaged extensively with payers representing a substantial portion of U.S. commercial and Medicare Advantage lives about our clinical strategy, study designs, and endpoints. The feedback has been overwhelmingly encouraging. One payer highlighted AXPAXLI's expected durability as potentially game-changing, while another suggested it could be preferred over other anti-VEGF options. Comments regarding market expansion noted the immense value of avoiding blindness, while others stressed the importance of consistent, uninterrupted therapy. These discussions reaffirm our beliefs about AXPAXLI's ability to deliver significant clinical differentiation, expand access, and redefine value in retina care by enhancing outcomes while possibly decreasing overall care burdens. Regarding our SOL registrational program for AXPAXLI in wet AMD, we have seen outstanding performance thus far. In SOL-1, I’m excited about the ongoing study’s progress, including patient retention and monitoring. To date, more than 95% of participants have remained in the study, which is almost unprecedented in retina trials. Additionally, our analysis shows over 95% of rescue events have adhered to the prespecified criteria, highlighting the commitment of our sites and demonstrating that patients and physicians are aligned with the protocol’s design. This adherence is likely to yield a robust data set when we analyze the results in early 2026. Protocol compliance is critical to ensuring that our data can withstand rigorous regulatory scrutiny. Additionally, the SOL-1 trial is overseen by an independent data safety monitoring committee, and there have been no safety issues observed to date, which is worth reiterating. SOL-R continues to progress alongside with its 6-month screening and loading phase, which serves as an innovative strategy to enhance patient selection and minimize risk in the study population. SOL-R has now achieved its target randomization of 555 subjects, marking another significant milestone and showcasing rapid execution from our clinical team along with substantial engagement from investigators worldwide. This speed and scale in recruitment highlight the demand among retina specialists and patients for durable therapies like AXPAXLI that promise improved long-term results while alleviating treatment burdens. To uphold our commitment to patients and investigators, we will continue to allow randomization of existing subjects in the trial's loading phase. We anticipate top line results for SOL-R in the first half of 2027 and will provide updates as appropriate. Collectively, the SOL program aims to deliver a comprehensive efficacy and safety package addressing critical concerns for retina specialists, thereby giving them the confidence to use AXPAXLI immediately upon approval. After completing two years of follow-up in either SOL-1 or SOL-R, subjects will have the chance to enroll in our SOL-X study for an additional three years. This open-label extension strategically aims to explore the long-term benefits associated with a non-pulsatile treatment like AXPAXLI, in addition to gathering long-term safety data. This study will evaluate important outcomes such as vision preservation, antifibrotic effects, and the implications of delaying AXPAXLI treatment in the control group. The data derived from SOL-X could further showcase the necessity of initiating AXPAXLI treatment early to avert poorer long-term visual outcomes while contributing to patient retention. Lastly, let's address diabetic retinal disease, encompassing diabetic retinopathy and DME. Our HELIOS program takes a bold and differentiated stance towards this condition. We are pursuing a broad label for diabetic retinopathy that includes DME, which is a complication of the diabetic retinopathy spectrum. This strategy allows us to tackle the entirety of diabetic eye disease with a single registrational program. The unmet need is staggering since diabetic eye disease impacts over 100 million people globally, with the majority remaining untreated. Even NPDR patients without DME are at high risk of irreversible vision loss if left unmanaged, and current treatments reactively intervene only after complications arise. We believe this paradigm needs to shift. Our HELIOS-2 and HELIOS-3 Phase III trials are designed to prove that early, infrequent treatment with AXPAXLI can positively influence disease progression. HELIOS-2 is being conducted under a SPA agreement with the FDA, reflecting our commitment to regulatory alignment and scientific rigor. These trials will assess 6 and 12-month dosing intervals to meet diverse patient needs. A key innovation in these trials is our primary endpoint, an ordinal 2-step DRSS endpoint at week 52, differing from the binary DRSS endpoints traditionally used in Phase III trials, which only account for improvement or worsening without recognizing all patient outcomes. This method disregards valuable data. Our ordinal analysis captures the entire range of responses—improvement, stability, and worsening—allowing every patient to contribute valuable data for analysis. This approach offers several advantages: it aligns with real-world treatment objectives, enhances statistical power, requires smaller sample sizes, and improves the likelihood of success compared to other endpoints, being fully aligned with FDA guidance in our HELIOS-2 SPA. We explored other endpoints, like vision-threatening complications, but found them cumbersome and less effective. Ultimately, ordinal DRSS is not only more clinically relevant but also approved by the FDA, making it the right choice for showcasing AXPAXLI's disease-modifying potential. Following our announcement about this endpoint at our Investor Day, feedback from investigators and the retina community has been overwhelmingly positive, and we believe this approach signifies the future of diabetic retinopathy trial design. We expect this ordinal endpoint will set a new standard in the field. Unlike our wet AMD program, the HELIOS-3 trial incorporates sham injections due to unique regulatory requirements. DR trials differ from the FDA’s draft guidance for wet AMD, where sham injections are not suitable due to subjective primary endpoints impacted by masking. In DR, however, outcomes rely on objective retinal measures. Given the lack of a universal standard for NPDR, utilizing sham control is not just acceptable but essential for ensuring regulatory consistency globally, especially in regions without available therapies for this condition. Our design strategy allows us to pursue a unified DR label covering both NPDR and DME since DME is a complication affecting DR patients, and all individuals with DME inherently experience underlying retinopathy. In both HELIOS-2 and HELIOS-3, we intend to include participants with non-center-involved DME. Our Phase I study indicated that subjects with non-center involved DME showed improvement with AXPAXLI. This approach aims to eliminate the need for separate DME trials, effectively allowing us to address the entire spectrum of diabetic eye disease with a single registrational program. By focusing on a superiority-driven DR label that encompasses the full continuum of disease, we believe AXPAXLI can unveil a market opportunity that is transformative for patients, physicians, and payers alike. As we wrapped up the third quarter of 2025, we had around $345 million in cash, excluding approximately $445 million in net proceeds from our recent equity financing. The enthusiasm we saw for participation in that financing reaffirms the bold decisions we've made so far. Every decision taken at this company is made with confidence in AXPAXLI, our clinical strategy, and market potential. Our confidence is bolstered by encouraging external feedback, including from payers representing the majority of covered lives in the U.S. These conversations have reinforced the investor excitement and validated our strategic vision. They indicate that the market is preparing for a future that could be defined by AXPAXLI, one marked by better outcomes, lower burden, and heightened cost efficiency. Following our recent financing, we are now well-positioned, anticipating a cash runway extending into 2028, along with the financial flexibility to support top line data from both the SOL and HELIOS registrational programs, advance the SOL-X long-term extension trial, invest in manufacturing capacity and infrastructure, and prepare for commercial launch and global expansion in anticipation of potential AXPAXLI approval. We are functioning from an enhanced position of strength where every capital decision is proactive and made with conviction. When we consider all elements—our science, trial design, execution, and strategic vision—the path forward is clear. We are building Ocular Therapeutix around the principles that will redefine the retina experience: a potential superiority label setting a new standard of durability that exceeds incremental improvements, establishing lasting competitive differentiation and reducing exposure to pricing and therapy pressures; market expansion transforming a $15 billion market into a much larger opportunity by lowering treatment burdens, improving adherence, and reaching millions of untreated patients with wet AMD and DR; immediate adaptability providing a solution that integrates seamlessly into existing practices without necessitating surgery, additional steroids, or workflow changes—just a superior, longer-lasting treatment that fits how retina specialists currently operate. This strategy is more than a marketing idea; it's the foundation for our mission to redefine retina care. To recap the key takeaways from today: First, SOL-1 is on track for top line data in early 2026, maintaining excellent retention and trial structure, with the potential to enable a superiority claim for AXPAXLI in wet AMD; second, SOL-R has now achieved its target randomization of 555 subjects and is progressing toward top line data in the first half of 2027 using a real-world design; third, our HELIOS program is about to commence, incorporating a novel ordinal endpoint established per our SPA agreement with the FDA, which we believe is optimal for enhancing statistical accuracy; fourth, we continue to pursue a comprehensive diabetic retinal disease label, including DME, which could significantly broaden AXPAXLI's reach; fifth, our financial strength allows us to gather top line data from SOL-1, SOL-R, and HELIOS programs, pursue the SOL-X open-label extension study, and confidently prepare for commercialization; and sixth, through our focus on superiority, market expansion, and immediate adaptability, we are positioning ourselves not just to participate in the retina market, but to redefine it. At Ocular Therapeutix, we are bold in our science, courageous in our strategy, and relentless in our pursuit of excellence. Thank you for your time and continued support. We are now ready to take questions.

Operator Instructions. Our first question comes from Tazeen Ahmed with Bank of America.

Thanks for the very detailed update. I maybe wanted to get a sense of how you're thinking the initial label for wet AMD could look like? Because you're doing a lot of work among SOL-1, SOL-R, and SOL-X. So what would the initial label look like and what do you think would be attributes of the label that you would think would be competitive that may need to be added on later as more data comes in?

Thank you, Tazeen. Thanks for the question, a very appropriate and great question. And I'll start out by saying, of course, we're not in labeling discussions with the FDA as yet. But you can see that this company has strategically placed the clinical trials in such a way as we get, we believe, the best label in the history of our field. We expect our label to be a superiority label based on SOL-1. We believe that we'll have the flexibility of dosing every 6 months to every 12 months based on SOL-R and SOL-1. And we'll also have flexibility, obviously, of repeat dosing. That's what we expect from the initial label. Again, we're not in discussions with the FDA, as you can imagine. However, the other thing also that I'd like to note is that although this will not be in the label, remember that in the masking arm of SOL-R, we are going up against high-dose EYLEA. So although the randomization is 2:2:1, and although this is not for statistical analysis, we certainly will have the numeric data. So we believe that we'll have a great competitive advantage versus the second generation of anti-VEGFs with high-dose EYLEA as well. Tazeen, thank you again for the question.

Our next question comes from Tara Bancroft with TD Cowen.

So my question is on NPDR. So one really quickly, for the expected patient populations in the HELIOS trials. Can you tell us what percentage of the enrolled that you would expect to have that are non-center involved DME? And then the real question is, if you could maybe describe in a little more detail for us, what is it that underlies your confidence in having a very broad DME inclusive label beyond only the non-center involved, especially compared to a different approach of running separate DME trials altogether? Because in that, I think it would be helpful if you could also discuss whether the inverse could be true that successful DME trials could be inclusive of NPDR at all or not?

Tara, thank you for the question. Great question again. So as far as the first question is concerned, really a quick answer. The fact of it is that we don't know. And when the time is appropriate, we certainly will guide you as to the stratification of our baseline patients that we have enrolled. In regards to the second question, the first thing to look at is the data from the HELIOS-1 study. Recall that with a single injection of AXPAXLI, a single injection at week 48, every single patient with non-center involving diabetic macular edema improved. Again, every single patient with diabetic macular edema improved with a single injection. We've looked at these patients in every way that was presented in our Investor Day, including in terms of total volume, etc. And Peter Kaiser showed you every single patient and every single patient with a single injection improved. On the other hand, every single patient who was not treated in the control group got worse. So we have great confidence based on the HELIOS-1 data that patients with non-center involving diabetic macular edema will improve. Now again, we're not in labeling discussions, obviously, with the FDA. But what I can tell you is that historically, the FDA has given labels based on the disease itself. If you recall, in my last company with IVERIC Bio, we studied only patients with extrafoveal geographic atrophy. There wasn't a single patient that we studied with center-involving geographic atrophy. And yet, when you see the label of that drug, you will see that it's a broad label encompassing all of geographic atrophy. The same can be said of previous studies for diabetic retinopathy such as PANORAMA. The same thing could be said for visual limitations in clinical trials that have not extended to the label, such as going all the way going back to ANCHOR and MARINA. So we have great confidence that we will have a broad label that will encompass all of diabetic eye disease and that we will not need to do another study for diabetic macular edema. Recall also that it doesn't work the other way around, because every single patient with diabetic macular edema will have diabetic retinopathy, but not every single patient with diabetic retinopathy will have diabetic macular edema. So again, we have great confidence that we will never need to do another diabetic eye disease trial again for retina. We believe that we will obtain a broad label that will encompass not only diabetic retinopathy but all of diabetic macular edema. Thank you, Tara, for that question.

Biren, are you there?

Can you guys hear me?

Yes, please go ahead with your question.

Maybe, Pravin, on the SOL-R study, could you just talk about what percentage of patients were randomized from the screening phase? And for SOL-X, I understand on the open-label extension, you're going to enroll patients from SOL-1. But are SOL-R patients also going to be eligible to participate in SOL-X?

Biren, thank you again and thanks for the question. So as far as SOL-R is concerned, recall that what we have is a very thoughtful and long ramp. Recall also that if you look at every single study that's ever been done with an anti-VEGF, whether it be Lucentis, EYLEA, Avastin, Beovu, anything. What you see is a curve when you plot the visual acuity with a number of injections that looks identical, which is that after 2 injections, the visual acuity improves and then it stabilizes. Now what we could have done is simply to say after 2 or 3 injections, we'll go ahead and randomize patients in SOL-R, because we'll have a certain degree of confidence in regards to the stability. We didn't do that. We went way above and beyond. What we did was to say, okay, we will do 3 loading doses and we'll have a unique period, 2 observation periods, not 1 but 2, in order to weed out any patient who would be unstable with any fluctuations in the OCT of 35 microns or greater. And after that, we went ahead and gave 2 more loading doses and only then do we randomize. So it's a very long ramp. As far as the screen failures are concerned, Biren, that was your question, we haven't guided you to that as yet. We will when the time is appropriate in terms of giving you the baseline details. But as of yet, I'm just absolutely thrilled to report as we did this morning that we reached our target randomization of 555 patients. This is a credit not only to our clinical team, which has been just absolutely outstanding in terms of execution throughout this entire process with SOL-1 with SOL-R, and you'll see very soon with the HELIOS studies, but it's also a credit to the patients and to the PIs. And we're incredibly grateful to both that we've reached this point of target randomization. In regards to the open-label study, both studies, SOL-1 and SOL-R will funnel patients into the open-label extension. Again, we will have a lot of data that we will have in that open-label extension. I think one of the most important things that we will have is what the crossover patients will do. Now remember, the crossover patients will cross over after 2 years of pulsatile therapy. We don't believe that those patients will ever catch up. And the reason for that is that we know that fibrosis can be detected as early as 90 days after pulsatile therapy. And we believe that with 2 years of pulsatile therapy that will limit the patient's vision improvement. And we will have data showing that for the best long-term outcomes, it is necessary to start AXPAXLI from the very beginning. We believe that data will be very important. The other part related to this also is that in all studies, starting with the 7 UP study, for instance, long-term outcome has shown a gradual decline in visual acuity based on fibrosis and atrophy. And we believe that with constant suppression that AXPAXLI will provide, we will see continued visual acuity improvement and stabilization, which will also add to the long-term outcomes that will benefit from immediate treatment with AXPAXLI and continuation of AXPAXLI with long-term constant suppression of VEGF. Thank you, Biren, for your question.

Our next question comes from Colleen Kusy with Baird.

Congrats on all the progress. Just as we're getting a little bit closer now to the SOL-1 data, just what details would you expect to share in the SOL-1 top line? Specifically, would you include 6-month BCVA? And what do you think will be the most important data points from SOL-1 that will help give us confidence in the read-through to SOL-R?

Colleen, thank you for your question. A great question, which I'm sure is on everybody's mind. Here's what I would say. Look, what we have done and what we have said is that we are very strategic in terms of planning these studies and our expectations of what the goal of these studies are. The sole purpose of SOL-1 is a superiority label, that's what we're pursuing. The purpose of SOL-R is clinical relevance. And the purpose of SOL-X is to provide long-term data to support both of these things. We also recognize what the challenge of SOL-1 is. We've recognized the challenge that it is to go ahead and show you data in our secondary and exploratory analyses that will give you even more confidence in the success of SOL-R. We understand that challenge. We will absolutely meet that challenge. We have not guided you as to what we will show you as yet, but we certainly understand what we need to do with the card turn in terms of the narrative of a positive SOL-1 study. But let me also say that while we will provide you even more confidence in the success of SOL-R, there should already be a great deal of confidence that SOL-R will succeed based on several factors. First is the derisked patient randomization that I've already spoken to, which has really the longest ramp, the most thoughtful derisking that I've ever seen of any study. And the second one is pertaining to the trial design is the endpoint. It's a 56-week endpoint. It's a singular endpoint that we believe is absolutely optimal for us. Again, it's a singular 56-week endpoint. But to summarize, Colleen, what I would say is we understand the challenge. We will absolutely meet the challenge. We will provide you even more confidence based on the SOL-1 card turn that there will be a positive SOL-R study. Thank you for the question.

Our next question comes from Sean McCutcheon with Raymond James.

Maybe a quick one for me. Can you speak to the progress of getting the NPDR studies up and running? I know you're using a similar site footprint to the wet AMD program? And how do you anticipate that accelerating those studies?

Thank you for the question, Sean. The process began right after the race for NPDR, and we are fortunate to have excellent sites worldwide. The results of SOL-1 and SOL-R reflect that. Many of the same sites are involved, along with some additional ones. We have staff in the company with significant expertise who have trained many people at these sites and know many in the industry. This puts us in a strong position to choose the best sites strategically. It’s important to remember where we started; there were doubts about the trial's recruitability, yet we exceeded recruitment expectations in record time. People also doubted the execution, thinking that doctors would deviate from protocols and patients wouldn't stay. We've provided data at our Investor Day and today showing that we have a retention rate of over 95% and an on-protocol rate also above 95%. These figures are remarkable for any trial in retina, especially one considered impossible to recruit. We often overlook the level of execution achieved by our team, which is due to both the clinical team's efforts and the strong relationships they have with the principal investigators and the entire sites. To answer your question, we will provide updates on the HELIOS progression. We are pleased with its progress, and you will hear more details soon.

Our next question comes from Jon Wolleben with Citizens JMP.

This is Catherine on for Jon. I just have another quick one for the DR program. I'm just wondering if there's any risks associated with using the ordinate 2-step DRSS endpoint, especially since you're considering using a smaller patient population. Is there any concerns regarding a higher placebo effect given kind of patient variability? I wonder if you could speak to that? And how do these risks compare to traditional endpoints?

Catherine, thank you for the question. It's a very appropriate and fair question, and it's something that we've looked into quite a bit. And what I can tell you without hesitation whatsoever is that we have great, great, great confidence in the ordinal endpoint. Now if you look at the talk that was given by Peter Kaiser in our Investor Day, you'll see that there are all kinds of scenarios that were put in, including the data that we have with the HELIOS-1 study. And as you can see, the level of success achieved by the data on the HELIOS study was overwhelming. So in this particular case, given the drug that we have and given the data that we have, we are very confident that with the ordinal endpoint that we will succeed. Again, if you look back at the HELIOS-1 study, what I would say as a clinician who's practiced for over 30 years and also with all the other clinicians that we have in this company, is that we've really never seen a situation where a single injection of a drug, again, a single injection of a drug after week 48 has results where every single parameter is in favor of the drug. And remember, this was just the drug. This was not a combination agent. EYLEA wasn't combined with this. This was simply AXPAXLI and nothing else, completely transparent. And what you will see there is not only in terms of the diabetic retinopathy score but also in terms of diabetic macular edema. And then we've looked at it in every single way possible, including the total fluid volume, including perfusion and every single parameter favored the drug with a single injection after week 48. So we have great confidence in the endpoint, and we have great confidence in the success of both HELIOS-2 and HELIOS-3. And remember also that HELIOS-2 has an FDA-approved SPA going with it as well to validate that study and validate the study design. Again, I also want to repeat that both HELIOS-2 and HELIOS-3 are superiority studies. Catherine, again, thank you for the question.

Our next question comes from Yi Chen with H.C. Wainwright.

For the HELIOS-2 trial, once started, how long do you think it will take to complete enrollment of 432 patients? Do you think NPDR patients would be relatively difficult to enroll because they are reluctant to get treatment in the first place?

Thank you for your question, Yi. We have already seen significant eagerness to enroll these patients, even before we announced the trials. When I was asked earlier whether we are using the same sites, I confirmed that there's a substantial overlap, along with additional sites. The sites are already expressing a strong interest in participating in this study due to the pressing need for these patients. We are enrolling individuals with advanced moderate to severe non-proliferative diabetic retinopathy, many of whom are symptomatic. While they may not have lost vision, they often experience blurry vision and are aware of the potential threat to their eyesight. There is a significant demand and excitement to offer a treatment that is sustainable for both patients and investigators. This treatment involves a single injection that we expect will last for a year. We are confident about the target being validated in other studies, which makes this study less risky. Particularly with the insights from HELIOS-1, we are very optimistic about the results. Therefore, we don't anticipate any issues in completing these trials efficiently. We are already making progress and will provide updates at the appropriate time. Thank you again, Yi, for your question.

We've reached the end of our question-and-answer session. There are no further questions at this time. I would now like to turn the floor back over to Dr. Dugel for closing comments.

Thank you very much. I'd like to thank all of you for your time today. I'd like to thank all of you for your diligence and for joining us. We look forward to updating you on our progress. If you have any follow-up questions whatsoever, please reach out to Bill Slattery, our Vice President of Investor Relations, and have a great day, everybody, and thank you again for your time.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.