Ocular Therapeutix, Inc.

We believe the strategy allows us to capture the full spectrum of diabetic eye disease with a single registrational program. The unmet need here is staggering. Diabetic eye disease affects more than 100 million people globally, yet the majority remain undertreated. Even among NPDR patients without DME, Disease progression leads to irreversible vision loss if left unmanaged. Current treatment paradigms are largely reactive, waiting until vision-threatening complications occur prior to intervention. We believe that must change. Our Helios 2 and Helios 3 Phase 3 trials are designed as superiority studies to demonstrate that early infrequent treatment with Expaxly can meaningfully alter the course of disease. Helios 2 is being conducted under a SPA agreement with the FDA, underscoring our continued commitment to regulatory alignment and scientific rigor. Together, these two trials will evaluate 6- and 12-month dosing intervals, providing flexibility to address diverse patient needs. A key innovation in these studies is our primary endpoint, an ordinal two-step DRSS endpoint at week 52. Historically, phase 3 DR trials have relied on binary diabetic retinopathy severity score, or DRSS, endpoints, counting only the percentage of patients who achieve a greater than or equal to two-step improvement or those who achieve a greater than set worsening not both while straightforward this method discards valuable clinically relevant data our ordinal analysis by contrast captures the entire spectrum of patient responses improvement stability and worsening allowing every participant to contribute data to the statistical analysis this approach offers several distinct advantages. It reflects real-world treatment goals to both improve disease and prevent worsening. It increases statistical powering, allowing more efficient studies with a smaller sample size. It potentially provides a higher probability of success compared to other endpoints considered. And it aligns fully with FDA guidance, as confirmed in our SPA for Helios 2. We evaluated other endpoints, such as vision-threatening complications or VTCs, but those present major limitations. VTCs are binary and event-driven, which require much larger sample sizes and longer durations to reach statistical power. They also reflect late-stage disease progression rather than early therapeutic benefit. In short, ordinal DRSS is not only more clinically relevant with a potentially higher probability of success, but it is also agreed to with the FDA from a regulatory standpoint. It's the right endpoint to demonstrate Xpaxley's disease-modifying potential in DR. Since announcing this endpoint at our investor day, the feedback from both investigators and the broader retina community has been outstanding. We believe this approach represents the future of diabetic retinopathy trial design, and we expect this ordinal endpoint will become the new gold standard for the field moving forward. Unlike our wet AMD program, The Helios 3 trial employs sham injections, and there are important regulatory reasons for that distinction. DR trials have very different regulatory requirements compared to the 2023 FDA draft guidance for wet AMD. Sham should not be used in wet AMD or even in central involving DME studies because they require subjective visual acuity primary endpoints where sham injections may not provide adequate masking and could influence outcomes. In DR, however, outcomes are based on objective retinal photographs, not subjective patient responses. Moreover, since there is no universal standard of care for NPDR, sham control is not only acceptable, but necessary to ensure global regulatory alignment particularly in countries without approved therapies for this population. Finally, our design strategy enables us to pursue a single unified DR label that encompasses both NPDR and DME. Because DME is a complication affecting a subset of DR patients, all patients with DME inherently have underlying retinopathy, In Helios 2 and Helios 3, we plan to include patients with non-center-involved DME. Subjects with non-center-involved DME demonstrated improvement with Expaxly in our Helios Phase 1 study. We believe this approach eliminates the need for separate DME trials and may position us to address the full diabetic eye disease spectrum with a single registrational program. By focusing on a superiority-driven DR label that captures the entire continuum of disease, we believe Xpaxly can unlock a market opportunity that is not just incremental, but transformative for patients, physicians, and payers worldwide. We ended the third quarter of 2025 with approximately $345 million which does not reflect approximately $445 million in net proceeds from our October equity financing. We were thrilled to see the enthusiasm for participation in our recent financing, validating the bold, opportunistic decisions we have made to date. Every decision that is made in this company is made from a position of confidence. in our drug, expaxily, and in our clinical strategy and in our market potential. Our confidence is compounded by consistently positive feedback we are hearing externally, including from payers who represent the vast majority of covered lines in the U.S. These discussions have reinforced the excitement we have seen from investors and further validated our triad-based strategy. These perspectives underscore that the market is already preparing for a future potentially defined by Xpaxly, one where potentially better outcomes, lower burden, and cost efficiency converge. Following our recent financing, we are now in an enviable position with an expected cash runway into 2028 and the financial flexibility for top-line data from both Sol and Helios registrational programs, advance Solex, our long-term extension trial, invest in manufacturing capacity and infrastructure, and prepare for commercial launch and global expansion in anticipation of a potential expatsily approval. We are operating from a position of increased strength. Every capital decision we make is proactive, not reactive, made from conviction, not constraint.

When you put it all together, our science, our trial design, our execution, and our strategic vision,

The path forward is clear. We are building ocular therapeutics around the triad that defines how we intend to redefine the retina experience. Potential superiority label, setting a new standard of durability that transcends incremental improvements, creating lasting competitive differentiation and potential insulation from pricing and step therapy pressures. Market expansion, transforming a $15 billion treated market into a much larger addressable opportunity by reducing burden, improving adherence, and reaching millions of untreated patients with wet AMD and DR. Immediate adaptability, delivering a product that fits seamlessly into existing practice.

No surgery.

no concomitant steroids, no change in workflow, simply a better, longer-lasting treatment that aligns with how retina specialists already work.

This triad isn't a marketing pitch. It's the blueprint of how we intend to redefine retina, period. To summarize today's key points, number one,

SOL1 remains on track for top-line data in the first quarter of 2026 with exceptional retention and trial integrity. Reaching statistical significance in SOL1 has the potential to enable a superiority claim on the expats label in wet AMD. Number two, SOLAR has now reached its target randomization of 555 subjects and is rapidly progressing toward top-line data in the first half of 2027, built on a real-world design with a de-risking patient enrichment strategy. Number three, our Helios program will initiate imminently, leveraging a novel ordinal endpoint established per the SPA agreement for Helios 2.0 We believe this is the optimal endpoint that increases statistical power and provides us a greater probability of success compared to other endpoints. Number four, we continue to pursue a broad diabetic retinal disease label, including DME, that could significantly expand Expaxly's reach. Number five, our financial strength gives us the flexibility to obtain top-line data from each of our SOL1, SOLR, and Helios programs pursue our SOLEX open-label extension study and prepare for commercialization with confidence.

Number six.

And finally, through the triad of superiority, market expansion, and immediate adaptability, we're building a company positioned not just to participate in the retina market, but to redefine it.

At Ocular Therapeutics, we are bold in our science, courageous in our strategy, and relentless in our pursuit of excellence. Thank you for your time and your continued support. Operator, We are now ready to take questions.

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. We ask that analysts limit themselves to one question so that others have an opportunity to do so as well. One moment, please, while we poll for questions. Our first question comes from Kazeen Ahmed with Bank of America. Please proceed with your question.

Good morning. Thank you for taking my question and thanks for the very detailed update. I maybe wanted to get a sense of how you're thinking the initial label for what A&D could look like, because you're doing a lot of work, you know, among fill 1, fill R, and fill 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? Thanks.

Thank you, Tazin, and good morning. Thanks for the question. A very appropriate, 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 to get, we believe, the best label in the history of our field. We expect our label to be a superiority label based on SOL1. We believe it will have the flexibility of dosing every six months to every 12 months based on SOLAR and SOL1. And it will 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 SOLAR, we are going up against high-dose ilea. So although the randomization is T2 and 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-VEGF with high-dose ilea as well. Kazim, thank you again for the question.

Our next question comes from Tara Bancroft with TD Cohen. Please proceed with your question.

Hi. Good morning. 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 NP-DR at all or not. Thanks.

Terry, good morning, and 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 One study. recall that with a single injection of Axpaxil, a single injection at week 48, every single patient with non-central 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 which way that was presented in our investor day, including in terms of total volume, et cetera, et cetera. 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 HeLEUS-1 data, that patients with non-central-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 label based on the disease itself. If you recall in my last company with iveric bio, we studied only patients with extra foveal 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 and 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.

Thanks so much.

Yeah, that's fantastic proxy to Iveric. That's very helpful. Thanks so much. Buren, are you there? Yes. Can you guys hear me? Yes. Please go ahead with your question.

All right. Thanks for taking my questions. Maybe, Parveen, on the SOL-R study, could you just talk about, you know, what percentage of patients were randomized from the screening phase? And, you know, for SOL-X, I understand, you know, 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? Thanks.

Barron, thank you again. Good morning to you 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 a study that's ever been done with an anti-VEGF, whether it be Lucentis, Ilea, Avastin, BFU, anything, what you see is a curve when you plot the visual acuity with the number of injections that looks identical, which is that after two injections, the visual acuity improves and then it stabilizes. Now, what we could have done is simply to say after two or three injections, we'll go ahead and randomize patients in SOLAR. 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 three loading doses and we'll have a unique period, two observation periods, not one but two, 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 two more loading doses, and only then do we randomize. So it's a very long ramp. As far as the screen failures are concerned, Barron, 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 Solon, with Solar, and you will see very soon with the Helio 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, SOL1 and SOLAR will funnel patients into the open-label extension. Again, we'll 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 two 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 two 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 X-PAX way 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 X-paxillie 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 Xpaxilin and continuation of Xpaxilin with long-term constant suppression of VEGF.

Thank you, Barron, for your question.

Our next question comes from Colleen Cousy with Baird. Please proceed with your question.

Great. Good morning. Thanks for taking our questions and congrats on all the progress. Just as we're getting still a little bit closer now to the SOL1 data, Just what details would you expect to share in the SOL1 top line? Specifically, would you include six-month ECVA? And what do you think will be the most important data points from SOL1 that will help give us confidence in the read-through to SOL-R? Thank you.

Yeah, good morning, Colleen, and 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 SOLE 1 is a superiority label. That's what we're pursuing. The purpose of SOLE R is clinical relevance, and the purpose of SOLEX is to provide long-term data to support both of these things. We also recognize what the challenge of SOLE 1 is. We recognize the challenge there 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 SOLAR. 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 a card turn in terms of the narrative of a positive SOLAR study. But let me also say that while we will provide you even more confidence in the success of SOLAR, there should already be a great deal of confidence that SOLAR will succeed based on several factors. First is the de-risk patient randomization that I've already spoken to, which has really the longest ramp, the most thoughtful de-risking 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 sole loan card churn that there will be a positive SOLAR study.

Thank you for your question. Helpful. Thank you.

Our next question comes from Sean McCutcheon with Raymond Jean. Please proceed with your question.

Hey, guys. Thanks for the question. 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 Web A&B program. You know, how do you anticipate that accelerating those studies?

Thanks. Sean, good morning, and thank you for the question. You know, look, the process started immediately after the raise for NPDR. We're very fortunate that we have fantastic sites all over the world. You've seen the results of that based on the execution of SOL1 and SOLR. And yes, many of the same sites are being used. There are additional sites as well. We are very, very fortunate that we have people in this company, as you know, with an enormous amount of expertise. Many of the folks here have trained many of the people that run these sites and certainly know pretty much everybody around the world. So we're in an envious position of being able to strategically pick the very best sites. And you've seen that again. You know, look, it's easy to forget where we were, Sean, not long ago. We had a trial that everybody said was not recruitable. We recruited way ahead of schedule in record time, and then people said, well, even if you did recruit that trial, there's no way that the execution is going to be good. Doctors are going to do whatever they want. Patients aren't going to stay. We've provided you data in our investor day and today, real numbers to show you how well the execution is taking place, that we have a 95% on protocol rate, over 95% on protocol rate, and over a 95% retention rate. Those things are absolutely unheard of for any trial in retina, let alone a trial that supposedly was impossible to recruit. And oftentimes we forget that. We forget the level of execution that this team has provided. And that's not only thanks to the clinical team, but that's also thanks to the sites that they've selected and the personal relationship that all of the team has with not only the PI but the entire site. So the answer to your question is we will give you guidance to the HELIOS progression. We're very pleased with the way that it's going, and you'll hear more details to follow.

Thank you, Sean, for the question.

Our next question comes from John Wollobin with Citizens JMP. Please proceed with your question.

Hi, this is Catherine on for John. I just have another quick one for the DR program. I'm just wondering if there's any risks associated with using the ordnance two-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'm wondering if you could speak to that. And how do these risks compare sort of to traditional endpoints?

Catherine, good morning. 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 with 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 One study, And as you can see, the level of success achieved by the data on the Helios One study was overwhelming. So in this particular case, given the drug that we have, 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 One 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 a drug this was not a combination of agent ilea wasn't combined with this this was simply expaxly 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 in every single which way possible, including 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. Thank you.

Our next question comes from Yi Chen with HC Wainwright. Please proceed with your question.

Good morning, and thank you for taking my question. For the HEDOS-2 trial, when started, how long do you think it will take to complete enrollment of 432 patients? Do you think MPDR patients would be relatively difficult to enroll because they are reluctant to get treatment in the first place?

Yves, thank you for your question, and good morning to you. So, you know, we have already seen a great deal of inertia to enroll these patients. In fact, we saw that before we even announced the trials. As I was asked earlier on by John whether we're using the same sites or not, I said, yes, there was a great deal of overlap, including other sites. The sites have already been demanding this study. There is such a need out there for these patients. And remember, what we're enrolling is we're enrolling advanced severe, advanced non-proliferative diabetic retinopathy. So a lot of these patients are symptomatic. They may not have lost vision, but they certainly have blurry vision, et cetera. They certainly are knowledgeable that there's a threat to their vision. So there's a great deal of need out there and a great deal of enthusiasm to have something that is absolutely sustainable by both patients as well as the PIs. And this is completely sustainable. As you know, it's a single injection. If it does what we expect it to do, that will last for a year. We know that this is a target that's de-risked, that's validated in other studies. So we believe that this is a relatively de-risked study, and especially given what I just said about Helios 1, we're very, very confident in the results. So to answer your question, We don't think that there's going to be any issue whatsoever in completing these trials in a very efficient manner. This is already underway, and we will guide you when appropriate.

Again, thank you for the 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. Dugo 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.