Ocugen Inc Aktie

Good morning and welcome to Oxygen's second quarter 2036 financial results and business update. All participants are in listen-only mode. Following the speaker's commentary, there will be a question-and-answer session. I will now turn the call over to Chris Clark, Oxygen's Head of Communications. You may begin.

thank you operator and good morning everyone joining me on today's call and webcast is dr shankar musanari occijun's chairman ceo and co-founder who will provide a business update and an overview of our clinical and operational progress rita johnson green our chief financial officer is also on the call to provide a financial update for the quarter ended june 30th twenty Abhi Gupta, Executive Vice President of Commercial and Business Development, and Dr. Mohammed Janeed, who joined Ocugen as Chief Medical Officer in June, will be available to answer questions following the presentation. This morning we issued a press release covering our business and operational highlights for the second quarter of 2026. encourage listeners to review the press release, which is available on our website at ocugen.com. A replay of this call, along with the accompanying slide presentation, will be available on the Investors section of the Ockogen website. Please note that certain statements made during today's discussion may be forward-looking in nature, including those related to our clinical development pipeline, regulatory timelines, commercialization strategy, and financial information, and our anticipated cash runway. These statements reflect management's current expectations and are inherently subject to risk, uncertainties, and assumptions that may cause actual results to differ materially from those expressed or implied. We encourage you to review our filings with the Securities and Exchange Commission, including the risk factors detailed therein, for a more comprehensive understanding of these potential risks.

Finally, OxyGEN's quarterly report on Form 10-Q covering the second quarter of 2026 will be filed today. I will now turn the call over to Dr. Mussonari. Thank you, Chris, and good morning, everyone. The second quarter was a defining one for OxyGEN. The FDA cleared our phase three trial for Occio410 to initiate dosing in geographic atrophy patients and granted RMAP designation for the program, It signed a binding term sheet with Roots Pharmaceutical to negotiate an exclusive license for Occy 400 and retinitis pigmentosa across the Middle East and North Africa, MENA region. And from the closing of 130 million convertible notes financing, we extended our cash runway into 2028, now able to support all three of our late-stage programs. Before I walk through the quarter, I want to step back, because OccuGEN's potential is worth putting into context.

For more than a decade, gene therapy in ophthalmology has been confined to a single gene, a single mutation, and a single small patient population. Our modified gene therapy platform takes a fundamentally different approach. Rather than targeting individual mutations, it is designed to address the root cause of complex complex retinal diseases by modulating master regulators, nuclear hormone receptors that govern multiple gene networks. The platform is gene agnostic, inherently multifactorial, and designed to deliver a durable benefit from a single, one-time subretinal injection. What this means in practice is that Occijn is not building three separate drugs. We're advancing one platform across three late stage programs, each targeting a major cause of blindness for which patients today have either no approved treatment whatsoever or therapies that demand chronic injections and carry meaningful safety burdens. Retinitis pigmentosa, RRP, Stargardt disease, and Geogarth's Atrophy, or GA, together affect approximately 3 million people across the United States and Europe, a combined patient population, and a commercial opportunity for larger than anything currently served by approved gene therapies and ophthalmology.

Across our pipeline, spanning phase one through phase three, we have treated more than 325 patients, including EAP, through multiple doses and indications, and we have not observed a drug-related serious adverse event. We remain on track to file three BLAs by 2028. This positions the first half of 2027 as a catalyst-rich window for OcciGen with the top line data for OCCI 400 and OCCI 410ST and our planned BLA submissions following over a short period. Let me walk you through how each program is advancing. Then I will hand over the call to Rita financials. Starting with Ocu410 for GA, a secondary to dry age-related macular degeneration or dry AMD, GA represents our largest commercial opportunity with approximately 2 to 3 million patients in the US and Europe combined. There are currently no approved treatments for GA Current approved therapies in the U.S. target only one complement pathway and require frequent intravitreal injections, which has been associated with treatment discontinuation in clinical practice.

PA is a multifactorial disease driven by four distinct pathways that contribute to the progressive degeneration of the macula, drusen, inflammation, oxidative stress, and complement activation. The currently approved therapies in the U.S. address only one of these four pathways, the complement system, which is partly why they have been unable to demonstrate meaningful functional outcomes for patients. Ocu410 operates differently. By delivering RORA, a nuclear hormone receptor that acts as a master regulator of retinal homeostasis. Ocufortin is designed to address all four disease pathways simultaneously with a single subretinal injection, has the potential to redefine the standard of care in this indication. recently received FDA clearance for RQ410 phase three registration trial for GA. The trial, Armada 3, is planned to be a global study of approximately 237 subjects, using an adaptive design powered at 95% for the primary endpoint, with the BLA and market authorization application filings targeted for 2028. We plan to initiate phase three by September 2026. This design is anchored by positive 12-month data from our Phase II Armada trial.

At the optimal dose, OQ410 delivered a statistically significant 31% reduction in GA lesion growth within the patient population of lesion size 2.5 mm2 and 17.5 mm2. The criteria to be used in our Phase III Pertil trials were control, approximately twice the benefit of approved complement inhibitors and from a single injection. We also saw a 27% preservation of the ellipsoid zone with a in the same patient population in no drug-related serious adverse events reported to date. Importantly, these phase two data help support the FDA's decision to grant or mat designation for OCU410. Turning to Ocu410ST for Stargardt disease. Stargardt is a pediatric onset retinal disorder affecting approximately 100,000 patients in the US and Europe, and roughly 1 million people globally. There are no approved therapies available for these patients today.

Ocu410ST is designed to address about 1200 pathogenic mutations in the ABCA4 gene with a single onetime treatment. On April 1st, we announced the completion of enrollment and dosing in our phase two, three, Guardian three total confirmatory trial, enrolling 63 participants. We expect the interim outcome decision for the first 50% of subjects at eight months in the third quarter of 2026 and top line phase two, three, data in the second quarter of 2027 with our BLS submission follow mid-2027. Moving to Octave 400 for RP, the Phase III Limelight Trial is the first and largest genetic medicine registration trial for broad RP, spanning more than 30 genetic mutations. Approximately 300,000 people in the U.S. and Europe are living with RP, which is caused by mutations in the blood. and more than 100 genes. The only approved gene therapy for RP today targets a single gene, RPE65, which accounts for less than 2% of all RP cases. RQ400 is designed to provide a therapeutic option for all RP patients and that is a fundamentally different commercial opportunity.

Enrollment in the limelight is complete with 140 patients randomized 2 to 1 treated versus control across the row. and gene agnostic columns spanning more than 30 genetic mutations associated with early to late stage RP, including pediatrics. The breadth of the population intended to validate the gene agnostic mechanism of action of our novel modified gene therapy platform. The primary endpoint is 12-month change in visual function assessed by luminance dependent navigation assessment or LDNA. Subjects are followed for one year post-dosing for the primary endpoint analysis. Top line phase three data is expected in the first quarter of 2027, advancing ARCHIV 400 to a potential approval in the fourth quarter of 2027. FDA feedback confirmed that the path to rolling BLA submission remains tied top line data expected in the first quarter of 2027. On the manufacturing side, our process performance qualification, PPQs, badges are complete, supporting BLA and commercial launch supplies.

Brand planning and marketing initiatives led by Abhigapta, our EVP of commercial and business development, continue to scale in preparation for launch. We also advanced our global commercialization strategy for OCCI 400 during the quarter. In July, we signed a binding term sheet with Root Pharmaceutical and its strategic partner, Al Dhow International Holdings, for exclusive rights to OCCI 400 in the Middle East and North Africa. We are active on the BD front to find other global partners for regional commercialization partnerships where RPE is most prevalent. Here is a snapshot of the market opportunity across all three late stage development programs. While OCCU 410 for GA represents our largest commercial opportunity, we believe all three programs have the potential to generate significant revenue while addressing areas of substantial unmet medical need. As we continue advancing our pipeline, we're also building the foundational commercial capabilities to support future global access.

Our efforts are focused on five key areas. First, we're in discussions with CMS and peers to establish early market access and reimbursement strategies. Second, we continue to identify and evaluate specialized centers of excellence with expertise in subretinal surgical procedures that could support future treatment delivery. Third, we are mapping the patient journey from diagnosis through treatment and long-term follow-up with the goal of facilitating a seamless experience for patients, caregivers, and healthcare providers. Fourth, we are assessing manufacturing, supply chain, and distribution requirements to help ensure operational readiness. Finally, we are beginning to build out our commercial infrastructure, including our marketing and sales capabilities as we ramp up for launch. With that, I'll turn the call over to Rick,.

Rita for the financial update. Rita? Thank you, Shankar. Good morning, everyone. The total operating expenses for the three months ended June 30, 2026, for $17.9 million, and included research and development expenses of $10.7 million, and general and administrative expenses of $7.2 million. This compares to total operating expenses for the Three months ended June 30th, 2025 of $15.2 million, which included research and development expenses of $8.4 million and general and administrative expenses of $6.8 million. Total operating expenses for the six months ended June 30th, 2026. were $37.3 million and included research and development expenses of $21.9 million and general and administrative expenses of $15.4 million. This compares to the total operating expenses for the six months ended June 30, 2025, Of 31.2M dollars, which included research and development expenses of 17.9M dollars. And general and administrative expenses of 13.2M dollars. Occupied reported a 7 cent net loss per common share for the 3 months ended June 30th, 2026. compared to a $0.05 net loss per common share for the three months ended June 30, 2025.

In our capital position, following the closing of the $130 million convertible notes financing, the company's cash, cash equivalents, and restricted cash totaled $100.4 million as of June 30, 2026, extending our cash runway into 2028. The company has 339 million shares of common stock outstanding as of June 30th, 2026. That concludes my financial update. Shankar, back to you.

Thank you, Rita. The second quarter was a quarter of execution. The remainder of 2026 is poised to be impactful. We expect the ARC-IV-10-ST interim outcome decision in the third quarter, and we expect to initiate the ARC-IV-10 phase III trial in this quarter. Looking to 2027, we expect top line data from both RQ400 and RQ410ST in the first half of the year, followed by our planned BLA submissions. Each of these milestones brings us a step closer to delivering on our commitment to three BLAs by 2028, offering and potentially life altering improvement to patients coping with blindness causing diseases. I want to thank our investigators and patients who have trusted us with their participation and our shareholders for their continued belief in our mission to advance cures for blindness.

We'll now open the call for questions. Operator? Thank you. Ladies and gentlemen, we will now begin the question and answer session. And at this time, I would like to remind everyone, in order to ask a question, please press star followed by the number one on your telephone keypad. And if you would like to withdraw your questions, simply press star one again. Again, if you would like to ask a question, press star 1 on your telephone keypad. Our first question comes from the line of Michael Ockenwich with Maxim Group. Please go ahead.

Hey there, thank you so much for taking my questions and congrats on all the great progress. Good. Thank you, Michael. So, I wanted to ask, you now have a handful of international partnerships, which makes OCU 400 a truly international program at this point. So I just wanted to see if you could share the regulatory plans in particular for ex-US jurisdictions, what's required there, and how those timelines could vary versus your BLA path.

Michael, what we have with RQ400, we got alignment from EMA in addition to FDA with the same that single trial we're doing in the US is good for approvals. And across the globe, for orphan gene therapies, typically they get approval based on U.S. approval. So everything will be linked to our U.S. FDA approval in MENA and other regions.

All right, thank you. And then I wanted to see also if you could just highlight some of the key differences in the trial design between our MODIC-3 and the Phase II armada trial. I let our CMO, Dr. Zinni, answer that.

Thank you, Michael. Regarding Armada 3, which is our global phase 3 trial for GA, which we just got the approval from FDA, you know, just recently to be initiated this quarter, the phase 3 trial designed for Armada 3 will be one treatment arm with OCU410 versus a control will be two to one randomization allocation and that day to follow each subject up to 12 months. And this is where we're going to be looking at the primary efficacy endpoint plus other key functional endpoint. The RMATA one, the earlier phase one to GH, trials was similar on the efficacy. So we should expect similar outcome here. We're going to look, the numbers obviously is different. We're going to be enrolling in our Model 3 close to 237 subjects into one allocation. It's going to be global. We're going to go ex-US, we're going to go to Europe and other territorial part in the world.

But the primary endpoint will be very similar, so we should expect to see similar trend what we saw from Armada 1, the phase 1, 2 AJA trial.

All right, thank you. And then just one last one from you before I hop back into the queue. So it looks like in Stargardt, there is a chance that we'll have an approved therapy sometime around when you'll be completing your own BLA filing. So it'd be a chronic therapy versus a one time, but to ask if how important the pricing on other therapies, since we don't have any pricing comps, would be to inform your own pricing strategy and if there's any way that we can think about how to translate pricing between a chronic ongoing therapy and a one-time therapy. Okay.

Yes, good question Michael. I think the way you look at it is our treatments are one and done treatments potentially. So that will have a different pricing structure than ongoing chronic therapies. Number two, everything will be dictated by data. And if you have a safe one-time treatment, I think our gene therapies, once again, we're still collecting data. As you can see in some of the patients in RP, and as they approach like second year, third year, they're improving further. So the current therapies, if the oral therapy comes to the market, what patients need to do patients, providers are going to look for? Is the therapy just reducing the the degeneration of the disease, or in some patients, is it stalling it? Is it has potential to reverse it in some patients? At least, you know, with our modified gene therapy in some of the patients who are seeing all those trends. So that could be a big differentiating factor.

And also as you know, Stargardt impacts a lot of pediatric patients. And the current clinical trial they're conducting focuses on 12 plus. And our clinical trial focuses on three plus. So there are a lot of differentiators. So whenever we come for pricing, because of the differentiated disruptive technology platform we have, and obviously everybody will focus on safety, efficacy, and one and done treatment, there'll be more compliant for anyone. So I think all those factors will be rolled in. So I don't think we'll be truly comparing praising what the other chronic therapies are doing.

If you have a me too product, the answer is yes. But if you have truly a definitively disruptive technology, which is completely different, it'll come, we can praise it on its own merits.

Alright, thank you. I appreciate the additional call. Our next question comes from the line of the IHM Mechanical Genuity. Please go ahead.

Hey, guys, my congrats on all the progress as well. Just to keep going on the Stargardt discussion, Shankar, since you mentioned it, can you talk about a little bit more, I guess, around the TPP here and the potential to show kind of reversal of disease and improvement in visual acuity? Is that something that is reasonable to expect given the duration of follow-up in the ongoing Phase 2-3 study? And I guess if so, is there anything that was done in terms of entry criteria to maybe enrich for that outcome as far as patient baseline characteristics?.

I will ask Dr. Ghani to talk a little bit about baseline characteristics, then I'll answer the other question. Go ahead. Thank you, Shankar. Hi, Whitney. Yes, happy to answer. So our population was definitely broader than other competitors. Just to highlight, first, we included patients from early to late stage target disease. That's number one. As Shankar just mentioned, too, we include subjects, you know, are younger than, you know, young adults. We included, you know, subject, you know, three plus years of age, so that's a very broad population. As you know, for Stargardt, the earlier the better, especially if it's a progressive retina generation disease.

The lesion size, also included in our trial, the phase 2, 3 guardian trial, was more broader than what we saw with others. And our lesion size can include smaller lesion, also larger lesion. So we have a broad spectrum, and that's also going to be aligned with our early, late stage strategy for the disease. We already included some of the other the subject in our phase 2-3 trials. So we will be excited to see the data. In addition to the gene mutation, specifically, we include all the variants and all the other specific mutations included in the ABCA4-related retinopathy. So it includes SORGET and others as well.

So this is also on the disease indicator. it's overall. Based on your point about the functional, I think this is going to be a critical. So we saw from our phase one data that we just published at the iNature early in the year, we saw a very clear structure, slowing in the structure progression in the in those patients, and also we saw functional benefit in those patients. And as you remember, as you know, in Stargate disease, the first target is to hold that progression, to stop losing more retinal structure and function, which we achieved in our prior trial. The second goal, which will be the upside here, the ultimate goal to reverse that tide, try to improve on the disease outcome. And we saw that in our phase 1, 2. We saw some of the patients did improve in visual function.

The gain was fixed letters close to one line between the three untreated eyes. So we felt also very excited about the functional gain in the patient population. So that's kind of where we think, you know, the big differentiation, the broader application of our molecule. Whitney, just to clarify, the primary endpoint, because it's a one-year trial, it's not a two-year trial, it's still a lesion. Then there are some.

secondary visual function will be monitoring. In addition to that, at the time of filing, we continue to monitor early stage phase one patients, and so we'll have long term data in those patients still.

GOT IT. REALLY HELPFUL. AND THEN JUST LAST QUESTION AND MAYBE RITA, THIS ONE IS FOR YOU. CAN YOU HELP US UNDERSTAND HOW YOU'RE THINKING ABOUT CASH GIVEN THE EXCITING PROGRESS WITH THE GA STUDY AND THE ABILITY TO START THAT STUDY IN SEPTEMBER, I THINK YOU SAID. IF THERE IS A NEED TO KIND OF PULL LEVERS TO EXTEND THE cash runway further. How should we think about maybe the startup of GA versus commercial prep for RP or Stargard and just kind of how you guys are thinking about those different levers if needed? Thanks.

Yes, thank you, Whitney. So, first of all, I mean, our primary goal is to make sure that we are, you know, minimizing shareholder dilution, but evaluating our opportunities in order to raise capital, just as you said, in order to bring these novel products to patients. So, just first of all, we have cash runway into 2028. And so I just want to remind everyone of that, which gives us the confidence to execute our, you know, our clinical state, our late stage products that we have, and then progress to BLA submission for both OCU410 and OCU410ST in 2027, with the potential to commercialize OCU400 by the end of the year. in 2027. We do have some additional levers that we can pull. One, you know, we have the PRV for OCU410ST given the RPD designation that we have. And so, of course, we have the ability to sell that for somewhere between, you know, 100 to 200, even prior to approval. And that's something that we are evaluating.

We also have various business development deals that we are looking at, you know, from a globalization perspective. We're looking at XUS for both ACCU 400, ACCU 410ST, and even GA, right, just depending upon what that term sheet looks like. So always looking for, you know, potential deals that we can make in order to, you know, again, just minimize that dilution. We also have the Janice Henderson warrants, right? There's another 10 million warrants at $1.50 strike price, which could bring in another $15 million, and those warrants expire in August of 2027. And then, of course, you know, we anticipate a, special meeting, right shares, which will give us the ability to raise additional equity if we decide to do so. So again, you know, just looking at both non dilutive as well as dilutive options in order to make sure that we are able to bring these amazing and novel products to patients as well as looking at maximizing shareholder value.

Very helpful, thank you. Our next question comes from the line of Charles Wallace with HDWayGuard. Please go ahead.

Hi, this is Charles from HC Wainwright. I'm for RK. Thanks for taking my question. Maybe a question on Armada 3 design. So it seems like based on the prior, based on the prior earnings call, the study has been a little bit resized. I think previously you said it would be about 300 patients and now it's 237 patients. So I was just curious if this was something the FDA specifically asked for or if this was something you proposed And then also if the assumptions change based on effect size, variability, dropout, or the narrower lesion size compared to the phase two.

Yes, we had a discussion with the agency, the FDA, so all this being aligned and discussed with the FDA. But to answer your question specifically, it was based on all the sample size estimation and also the power calculation we did. So the estimate you're citing, the 300, was based on estimate, but when we saw the effect site based on our Armada 1, the Phase 1-2 trial. And as we discussed today, we saw the 31 percent reduction in the medium dose, the optimal dose, which is the one we are taking forward. When we did our calculation based on that, we saw, you know, the 237 total population to be enrolled will give us 95 percent power in our PIVOT trial. All these pieces have been discussed with the agency. Obviously, it's based on the rate of change, the slope analysis for the primary efficacy.

So, the effect size, you know, based on what we saw from earlier trial was very positive and was strong enough that we end up, you know, with 237. Two-to-one randomization, as we mentioned earlier, 158 in the treatment arm and 6,000 and the control arm. So all this has been discussed and aligned, and as we announced today, we got the clearance from the FDA to initiate our phase three trial in the next few weeks.

Thank you. Very helpful. And then I guess for, I'm not sure if I'm And the rolling submission, so I think originally the guidance was to submit in the third quarter. And now I believe it's the first quarter after the limelight data came And, you know, I think I guess my question is, what kind of changed between submitting the nonclinical module earlier compared to after the top line at the limelight?.

Charles, I think from our perspective already, I mean, I think we're doing very well with our PPQs as we've mentioned. A lot of gene therapy companies stuck with CMC. We're ahead of the game. We used to commercial scale lots in phase three. We completed our PPQs on time. We got non-clinical and PPQ are done. So we have CMC non-clinical ready to go. I mean, obviously, this is where we We have to work with agency when they're comfortable.

And that's the timeline they gave us, and we're going to be fine with that. The reason is, I just want to clarify, it's good to have rolling submission that gives a head start for agency. It's for their own benefit. And if they want to wait until next year, I mean, we are ready to file it as soon as the top line comes for the pre-BLA meeting. We may still give them a head start of maybe a month or two months before we drop the clinical section. So however, I just want to clarify, until the final BLA is completed with the clinical section, the PDUFA date, the accelerated clock of six months doesn't start. I just want to clarify that. So once again, this is a collaboration between, you know, the sponsor and the agency.

In this case, of course, we respect their decision, whatever they are, because, you know, they have a lot of programs, a lot of workload, whatever the reasons are, we are fine with it. I think we're ready for more perspective and we will work with them closely in collaborative way and we're whenever we have a top line, we'll be ready to file it. Great, very helpful. It doesn't change any, yes, filing clock, as we mentioned before, second quarter, complete the BLA filing, anticipated approval in fourth quarter, six months accelerated clock.

Very helpful. Thanks for taking both questions.

Good morning and congratulations on the progress. Just to follow up on that last question, my understanding was that the BLA submission will be completed in early 2027 when the clinical module is filed. That's when you get the PDUFA date and the BLA. the approval launches based on that. But you also have rolling submission and have the option of filing the CMC and the other non-clinical modules before that. Is that still your plan?.

Yes. Yes, Robert, absolutely. Because based on agencies suggestion, recommendation, as soon as the top line comes out, we'll have a pre-BLA meeting. Right after that, we can file the two modules, non-clinical and CMC modules. So that will still give them a head start. Then as soon as the clinical module is done, when you file it, the pre-do for date starts. So that's basically our plan is to file that in second quarter, so six months' clock should be fourth quarter, approval clock.

Okay, terrific. Thank you for that. And at this time, we have no further questions. I would like to turn the call back over to the Oxygen team for closing remarks.

Thank you all for attending today's webcast. Really appreciate all our investors, shareholders, patients, providers. Thank you.

This concludes today's conference call. You may now disconnect. Have a good day.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Good morning, and welcome to Ocugen First Quarter 2026 Financial Results and Business Update. [Operator Instructions] I will now turn the call over to Tiffany Hamilton, Ocugen's Head of Corporate Communications. You may now begin.

Thank you, operator, and good morning, everyone. Joining me on today's call and webcast is Dr. Shankar Musunuri, Ocugen's Chairman, CEO and Co-Founder, who will provide a business update and an overview of our clinical and operational progress. Rita Johnson-Greene, our Chief Financial Officer, is also on the call to provide a financial update for the quarter ended March 31, 2026. Dr. Huma Qamar, Chief Medical Officer, will be available to answer questions following the presentation.

This morning, we issued a press release covering our business and operational highlights for the first quarter 2026. We encourage listeners to review the press release, which is available on our website at ocugen.com. A replay of this call, along with the accompanying slide presentation, will be available on the Investors section of the Ocugen website.

Before we begin, please note that certain statements made during today's discussion may be forward-looking in nature, including those related to our clinical development pipeline, regulatory pipeline, commercialization strategy and financial information and our anticipated cash runway. These statements reflect management's current expectations and are inherently subject to risks, uncertainties and assumptions that may cause actual results to differ materially from those expressed or implied. We encourage you to review our filings with the Securities and Exchange Commission, including the risk factors detailed therein for a more comprehensive understanding of these potential risks.

Finally, Ocugen's quarterly report on Form 10-Q covering the first quarter of 2026 will be filed today. I will now turn the call over to Dr. Musunuri.

Thank you, Tiffany, and good morning, everyone. Before I walk through the quarter, I want to discuss the $115 million offering of convertible senior notes that we announced yesterday. With the recent offering, the company is expected to have cash, cash equivalents and restricted cash of $112.1 million at closing, which includes the Avenue debt payoff. The company will use the remaining net proceeds for general corporate purposes and expect to extend cash runway into 2028. The offering is expected to close on May 7, 2026, subject to customary closing conditions and includes an option to retire the debt with the cash payment. If the remaining Janus Henderson warrants are exercised, the company will receive an additional $15 million in gross proceeds, increasing expected cash, cash equivalent and restricted cash to $127.1 million.

Now I would like to step back because Ocugen's potential is worth putting into context. For more than a decade, gene therapy in ophthalmology has been confined to a single gene, a single mutation and a single small patient population. Our modified gene therapy platform takes a fundamentally different approach. Rather than targeting individual mutations, it is designed to address the root cause of complex retinal diseases by modulating master regulators, nuclear hormone receptors that go on entire gene networks. The platform is gene agnostic, inherently multifactorial and designed to deliver durable benefit from a single onetime subretinal injection.

What this means in practice is that Ocugen is not building 3 separate drugs, we're advancing platform across 3 late-stage programs, each targeting a major cause of blindness for which patients today have either no approved treatment whatsoever or therapies that demand chronic injections and carry meaningful safety burdens. Retinitis pigmentosa, or RP, Stargardt Disease and Geographic Atrophy, or GA, together affect approximately 3 million people across the United States and Europe, a combined patient population and a commercial opportunity far larger than anything currently served by approved gene therapies in ophthalmology.

Across our pipeline, spanning Phase I through Phase III, we have treated more than 250 patients across multiple doses and indications, and we have not observed a drug-related serious adverse event. In our most recent readout, OCU410 demonstrated approximately twice the treatment benefit our currently approved therapies in GA delivered at onetime injection.

We remain on track to file 3 BLAs over next 3 years by 2028. And first of those OCU400 for RP will begin rolling submission in the third quarter of this year. This positions the first half of 2027 as a catalyst-rich window for Ocugen with Phase III top line data for OCU400, top line Phase II/III data for OCU410ST and BLA submissions all expected to converge for a short period. In the first months of 2026, we completed enrolment in 2 of our late-stage programs, delivered positive Phase II top line data in the third and are diligently working towards initiating our first BLA submission later this year.

Let me walk you through how each program is advancing. Starting with OCU400 for RP. The Phase III LiMeliGhT clinical trial is the only broad gene-agnostic RP trial and the largest known Phase III orphan gene therapy trial in the field. Approximately 300,000 people in the U.S. and Europe are living with RP, which is caused by mutations in more than 100 genes. The only approved gene therapy for RP today targets a single gene RPE65, which accounts for just 1% to 2% of all RP cases. OCU400 is designed to provide a therapeutic option for the remaining 98% to 99% of RP patients, and there is a fundamentally different commercial opportunity.

Enrolment in LiMeliGhT is now complete with 140 patients randomized 2:1 across the role and gene-agnostic arms covering over 25 genetic mutations associated with early to advanced stage RP, including pediatrics. The breadth of population is intended to validate the gene-agnostic mechanism of action of our novel modifier gene therapy platform. The primary endpoint is 12-month change in visual function assessed by Luminance Dependent Navigation assessment or LDNA. We plan to initiate the rolling BLA submission for OCU400 in the third quarter of 2026 and complete BLA submission by the second quarter of 2027. Phase III top line data is expected in the first quarter of 2027 with a potential FDA approval targeted for the fourth quarter of 2027.

On the manufacturing side, process performance qualifications, PPQ batches completion is on track for the second quarter of 2026 and brand planning and marketing initiatives led by Abhi Gupta, our EVP of Commercial and Business Development, continue to scale in preparation for launch. OCU400 continues to demonstrate encouraging long-term durability with the 3-year data supporting sustained improvement in visual function compared with untreated eyes. In the Phase I/II study, the treatment effect was maintained over time across evaluable subjects with a clinically meaningful mean changes in LLVA observed at years 1, 2 and 3 in both the multiple mutation and RHO subgroups.

Importantly, these results suggest the benefit is not limited to a single genetic subtype, reinforcing the program's gene-agnostic mechanism of action. From a safety perspective, OCU400 continues to show a favorable profile with no serious adverse events reported as being related to treatment. At the 3-year time point, 88% of treated evaluable subjects demonstrated either improvement or preservation in visual function relative to untreated eyes, highlighting both the durability and consistency of the response. Taken together, these data support the potential for OCU400 to deliver sustained clinical benefit over time in retinitis pigmentosa while maintaining a strong safety profile.

Turning to OCU410ST for Stargardt disease. Stargardt disease is a pediatrics onset retinal disorder affecting approximately 100,000 patients in the U.S. and Europe and roughly 1 million globally. There are no approved therapies available for these patients today. OCU410ST is designed to address over 1,200 pathogenic mutations in the ABCA4 gene with a single onetime treatment. On April 1, we announced the completion of enrolment and dosing in our Phase II/III GARDian3 pivotal confirmatory trial enrolling 63 participants in less than 9 months, well ahead of the originally planned time line. That pace reflects both the depth of unmet need in Stargardt disease and the exceptional engagement of our investigators and patient community.

The interim analysis is planned for the third quarter of 2026 with the top line Phase II/III data expected in the second quarter of 2027 and BLA submission to follow by mid-2027. OCU410STcontinues to demonstrate a favorable safety and tolerability profile with no product-related serious adverse events reported to date.

Turning now to OCU410 for GA, late-stage dry age-related macular degeneration. GA represents our largest commercial opportunity with approximately 2 million to 3 million patients in the United States and Europe combined. There are currently no approved treatments for GA in Europe. In the United States, approved therapies require 6 to 12 intravitreal injections per year indefinitely, carry meaningful safety risks, including conversion to wet AMD in roughly 12% of treated patients and face real-world dropout rates of nearly 40%. GA is a multifactorial disease, driven by 4 distinct pathways that contribute to the progressive degeneration of the macula. Lipid deposits/Drusen, chronic inflammation, oxidative stress and complement activation. The currently approved therapies in the U.S. address only one of these 4 pathways, the complement system, which is partly why they have been unable to demonstrate meaningful functional outcomes for patients.

OCU410 operates differently by delivering RORA, a nuclear hormone receptor that acts as a master regulator of retinal homeostasis. OCU410 is designed to address all 4 disease pathways simultaneously with a single subretinal injection, has the potential to redefine the standard of care in this indication.

In March, we reported positive top line 12-month data from our Phase II ArMADa clinical trial. The study enrolled 51 patients aged 50 years and older with the GA lesions in the foveal or non-foveal lesion randomized 1:1 to receive a single subretinal administration of OCU410 at the medium dose, high dose or no treatment in the control group. The optimal dose, which is the medium dose demonstrated a 31% reduction in lesion growth relative to control at 12 months with a p-value of less than 0.05.

To put this in context, currently approved intravitreal therapies have shown approximately 15% reduction at 12 months for Avacincaptad pegol and 22% reduction at 24 months for Pegcetacoplan OCU410 administered as a single onetime injection has shown the potential for an approximately twofold treatment benefit relative to approved therapies that require continuous chronic dosing regimens.

Across the treated population, 55% of treated subjects demonstrated a 30% or greater reduction in lesion size relative to control. We also observed a 27% slower rate of ellipsoid zone loss, which is structural biomarker that correlates with the preservation of photoreceptor integrity and visual function. On safety, OCU410 continues to demonstrate a safe and tolerable profile with no serious adverse events, no adverse events of special interest related to OCU410 reported to date.

We are now incorporating these results into an optimized Phase III trial design, including a targeted GA lesion size window and an adaptive design powered at greater than 95%. We are now on track to meet with FDA and EMA to align on the Phase III study design and reach regulatory agreement by the third quarter of 2026 with potential BLA filing by 2028. As a onetime treatment for life, OCU410 has the potential to eliminate the chronic treatment burden and patient fatigue associated with currently approved therapies and to offer a lasting solution for the 2 million to 3 million patients in the U.S. and Europe living with GA.

Let me briefly update you on our programs. For OCU200, we completed Phase I clinical trial enrolment in the first quarter of 2026 and no serious adverse events or adverse events related to OCU200 have been reported to date. On OCU500, our first-in-class inhaled mucosal COVID-19 vaccine candidate designed to be administered via inhalation and intranasal delivery, NIAID intends to initiate the OCU500 Phase I clinical trial in the second quarter of 2026.

Today, we want to highlight the meaningful progress across our retinal gene therapy pipeline and the important milestones we expect over the next several quarters. For OCU400 in retinitis pigmentosa, we remain on track to begin a rolling BLA submission in 2026 with Phase III top line data expected in 2027 and the potential for BLA and launch thereafter.

For OCU410ST in Stargardt disease, we have completed dosing ahead of schedule in our pivotal Phase II/III GARDian3 trial with interim analysis expected in the third quarter of 2026 and top line results anticipated in the second quarter of 2027, followed by a planned BLA submission.

For OCU410 in geographic atrophy, we continue to advance toward Phase III development following encouraging Phase II data with the program expected to move through Phase III enrolment toward BLA submission by 2028. Taken together, these milestones reflect a disciplined multi-program strategy designed to create value through a series of increasingly important clinical and regulatory readouts.

I'll now turn the call over to Rita to provide an update on our financial results for the quarter ended March 31, 2026. Rita?

Thank you, Shankar. Good morning, everyone. Total operating expenses for the 3 months ended March 31, 2026, were $19.4 million and included research and development expenses of $11.3 million and general and administrative expenses of $8.1 million compared to total operating expenses for the 3 months ended March 31, 2025, of $16 million that included research and development expenses of $9.5 million and general and administrative expenses of $6.5 million.

Ocugen reported a $0.06 net loss per common share for the 3 months ended March 31, 2026, compared to a $0.05 net loss per common share for the 3 months ended March 31, 2025. The company's cash, cash equivalents and restricted cash totaled $32.2 million as of March 31, 2026, compared to $18.9 million as of March 31, 2025. The company received $37.5 million in gross proceeds, inclusive of $15 million due to exercise warrants in the first quarter of 2026. With the recent offering, the company is expected to have cash, cash equivalents and restricted cash of $112.1 million at closing, which includes the Avenue debt payoff and expects to extend cash runway into 2028. The company had 338.3 million shares of common stock outstanding as of March 31, 2026.

That concludes my financial update. Shankar, back to you.

Thank you, Rita. The first quarter of 2026 was a quarter defined by execution. We delivered positive 12-month Phase II data for OCU410 in GA, completed enrolment and dosing in the GARDian3 trial well ahead of schedule and continued advancing OCU400 towards its rolling BLA submission later this year.

Looking ahead, the remainder of 2026 is poised to be consequential with multiple meaningful inflection points. We expect interim outcome analysis from GARDian3 in the third quarter, regulatory alignment with FDA and EMA on the OCU410 Phase III design in the third quarter and the initiation of our first BLA submission for OCU400 also in the third quarter. Each of these milestones bring us a step closer to delivering on our commitment of 3 BLAs by 2028.

I want to thank our employees, investigators and patients who have trusted us with their participation and our shareholders for continued belief in our mission to advance cures for blindness.

We'll now open the call for questions. Operator?

[Operator Instructions] Your first question comes from the line of Leland Gershell from Oppenheimer.

This is Jason on for Leland. It seems like it's gearing up to be an exciting year for OCU400 in the retinitis pigmentosa. And with that, could you give us a sense of what's being submitted for the rolling BLA versus the full BLA next year? And how are you thinking about the pre-commercialization activities going into 2027 launch?

Yes. So the rolling submission, as we stated, will start with nonclinical section module. And also, we're completing our PPQ lots from CMC manufacturing perspective. That module will also be submitted this year. And next year, as soon as the top line results come in within weeks after that, the final clinical module will be submitted, and that will trigger a PDUFA date of 6 months clock, expected to get the approval in the fourth quarter and launch.

From a commercial perspective, there are multiple things we are doing, as we mentioned before, we're working on one thing on the pricing, the government, [ CMS ]. And second step is, of course, as a company, we have established very standard way of treating these patients with our surgery procedure, which we use in clinical trials to minimize any risk to the patients. So we want to really identify the centers for excellence where our gene therapy can be administered. So that's what we're working under the second step.

And the third step is, of course, gearing up for sales and marketing and really commercial plans. I think we're working on the strategy. And typically, you start that work a year before. So later part of the year, getting into the early next year, that's when we'll start bulk of the commercial work.

Your next question comes from the line of Michael Okunewitch from Maxim Group.

Congrats on all the great progress you're making. I guess just to start off, I'd like to see, given how quickly the Stargardt program has been moving, how close together are you expecting an RP and a Stargardt approval could occur? And then are there any additional commercial considerations you're evaluating with the possibility that you will be kind of ramping both of these launches contemporaneously?

No, good question. I mean if everything goes according to the plan, they could be within 6 months of each of them. Obviously, from launch or commercial perspective, again, we're targeting the same centers for excellence for gene therapy administration. The same surgeons are going to administer for administering for RP.

So in fact, actually, it helps us as a company, economies of scale and how we are setting it up for RP, and that will always help with Stargardt disease. So when Stargardt is going to come later within 6 months, we should be in a great shape from a commercial perspective and launch perspective.

All right. And then how much overlap is there between the LiMeliGhT and the GARDian studies? Are they largely at the same centers? Or if you take them combined, do they reach a broader swath of the overall market?

Go ahead, Huma.

This is Huma Qamar. I'm going to take this question. Good question. So both represent inherited retinal diseases, of course, Retinitis pigmentosa. We have almost the same centers. There is a single subretinal injection. There is an overlap. However, there is no approved product for Stargardt, and we do have a huge unmet medical need in terms of RP as well. So the centers are almost the same. And also, as Shankar has mentioned, centers for excellence. There is an increased demand for -- as we have now closed the enrolment for both the programs to go as fast as we could per the protocol. And there will be some overlap, but there are quite a few more centers that we have identified as well.

So the current clinical centers, Michael, just to answer, close it out, are not good enough for commercial. They're good. but we need a lot more for commercialization.

Your next question comes from the line of Robert LeBoyer from NOBLE Capital Markets.

Congratulations on all of the progress that you've been making. My question has to do with the marketing and you mentioned of centers for excellence. My understanding was that the product is something that can be administered by any ophthalmologist and anyone who treats patients and is very easy to fit into the current practice. So I was wondering about the centers of excellence and how you're going to launch the product, if it's going to be a broad launch or focused on specific areas or treatment centers in the marketplace.

Yes. I mean, good question. I mean, obviously, it's vitrectomy. It's not a big surgery. I think any of our 2,500 trained, well-trained retinal surgeons in our country can do that. However, it's a one-and-done treatment. It's a onetime administration for life. So we want to make sure whatever center they're going to participate in the commercial and that they get trained on the same surgical manual we've been using in the clinical trials, which has been worked successfully. So that's the goal.

I mean, once again, I just want to clarify -- this is not a complex surgery. And any of those surgeons, the 2,500 smart retinal surgeons can do this. But as a company, we just want to make sure we train a group of people. I mean, whatever centers we need for commercialization, it could be 100, it could be 200. We want to make sure those centers are very well trained, and so they follow the same procedure across the board for consistency and patient safety.

And just my understanding was that anyone who is a retina surgeon can administer OCU400 without any special training. Is that correct? Or just what is the difference between the clinical trial and actual practice?

So I can answer that, Robert. Good to hear from you. So yes, it's a vitrectomy, which is pretty common as part of standard of care. This is not a new treatment or anything that they have not done. What Shankar is mentioning here is actually, every product has its specifications. So when we are launching the centers of excellence, that would be the main centers that could further train down the next few centers, like down there. So the initial launch, definitely, we have all across, they are covering majority of the centers. And this is not a new treatment, new procedure or single subretinal injection that we are giving.

However, when we define centers of excellence, that's always like the initial ones that take the burden of like for the first launch and then go towards the next. So yes, you do not need any special training. This is pretty much standard of care, and we have vitro-retinal surgeons that are pretty good in doing this. The only difference is this there is, of course, with any product, you come up with the guidelines, and that's what they have to do.

And Robert, I think this is the first time, remember, we're not talking about going after 500 patients, 1,000 patients. We're going to go after hundreds of thousands of patients with our therapies. So there is the whole payer system and how you direct the patients. It's a new paradigm Ocugen has to establish. It's nothing like anybody has done before. I just wanted to make it very clear in gene therapy space.

Your next question comes from the line of Whitney Ijem from Canaccord Genuity.

Congrats on all the progress this quarter. First question, I guess, headed into the interim for the Stargardt study in the third quarter. Can you remind us, first of all, the powering of that study like what was assumed? And then what will -- what should we all be expecting to see in that readout? And then sorry, third part of this question is just what is the range of outcomes based on that data for the study moving forward?

Yes. I think Whitney -- so this is the outcome analysis. It's not really giving any interim analysis like we expect in our primary endpoint and secondary endpoint analysis. So this is done under strict guidance of data monitoring committee. So why do you do adapter design to minimize any further risk to Phase III clinical trial. In Phase III clinical trial, we have a true control arm, untreated arm, which will be compared with the treatment arm.

And so the DMC looks at predictive analytics and see the study is designed for 12 months. And at 8 months and 50% of the patients have completed, they're going to look at it compared to control arm. Are we going to meet the success? And if there is nothing to be changed, you continue. That's outcome number one. No changes. Top line results come out in the second quarter of next year. BLA will be filed a few weeks after that and then the clock starts for a PDUFA date.

The outcome number 2, I mean, we did recruit additional patients in the trial. I mean, obviously, anticipation of dropouts and all that. But if the analytics show you need to increase number by a certain number, we have to again recruit. I mean, that may have -- that means you have to monitor those patients for additional 1 year. So that has impact on the top line results in the filing.

And during that timeframe, we're also based on the discussions we had in the agency in the past, we have 2 options, either you increase the size -- and we can also look into adding an additional time point from 12 months, you also can add 16 months' time point. You can also look into predictive analytics and see if you're going to meet the criteria of making a success if you extend it to 16 months.

So those are the 2 options we have. Obviously, the [ DMC ] with a blinded staff Ocugen, they're going to look at it carefully and present these options to Agency and get the buy-in from FDA, which they have recommended these 2 options in the past. And then once the outcome is finalized by -- with the Agency's Congress, we're going to let the markets know. So just to sum it up, one of the outcomes is there's no change. We're on track. Everything is looking good. Another outcome is, yes, there is some delay, but the delay also minimizes any risk to the clinical trial. We're ingesting. So there's a delay of 6 months. So those are the outcomes we'll discuss with the market.

Got it. Okay. That's really helpful. And then going back to the powering question, what -- have you disclosed the powering of the study on the primary endpoint?

Yes. So basically, we have for the Stargardt disease, 51 subjects, 34 treatment 17 control and the adaptive design would be for 24, 16 treatment 8 control. And yes, it's adequately powered around 90% or more. And we are going to look at the powering once again once the adaptive analysis interim outcome is going to be there. However, we are sufficiently powered, keeping in mind the prevalence as well as the no approved product right now in market. So the interim outcome would be either sample size re-estimation or no.

Got it. Okay. That's helpful. And then just to double check, in terms of the range of outcomes, there's no, I guess, upside scenario, right, just to make sure we're fully thinking through all the scenarios. Best case scenario, things are on track. There's not like a best case, oh, we're going to end early or something like that, right?

Yes, that's right. Yes. I think -- I mean, unless -- yes, I mean, Whitney, if you look at many products which got approvals under -- some of them got approvals with 30 patients, right, with orphan diseases. I mean, obviously, with the -- as Huma stated, it's 50% reaching 8 months. Eight months, I think we have to be also be practical. I mean if it's a 1 year, it's a different story. But gene therapies for us, modified genes to start working, minimum, you need like 6 months to show something. And at 1-year timeframe, you really reach the effect side and everything else.

So obviously, again, the data will tell and we'll wait. For orphan diseases, you're right, if there's a significant unmet medical need, even sometimes in the interim, if you really hit it out of the park, agencies will consider that. But I also want to be practical about it. I think 8 months is for adjustment. But typically, it's good to look at it 1 year. One year itself, if you look at all our clinical trials compared to other things going on in the industry across all our 3 programs, we are doing 1-year trials compared to anybody out there. Most of the people do 2-year trials because we are able to show effect size, treatment effect and benefit in 1 year.

Yes. That makes perfect sense. Okay. And then just moving on a cash question. What does the new guidance into 2028 assume in terms of GA Phase III spend?

Yes, it's included within the -- the GA Phase III spend is included in the new cash runway into Q1 or into 2028. So yes, we do anticipate being able to cover the expenses for that trial.

Okay. Got it. And I guess, could you -- I know the conversations with the Agency are ongoing, but what was assumed in terms of size of that study just for cash reasons or any design characteristics you can talk about at this point just for -- again, from a cash estimation perspective?

It's a 300-patient global trial in U.S., EU and Canada together. And most of the patients are -- majority will be in U.S. because we have the existing centers. And so it's 2:1 ratio, 200 in treatment and 100 in untreated control. It's powered at over 95% the primary endpoint and 92% for EZ Ellipsoid Zone secondary endpoint. And it has an adaptive design at 150 patients reach 1 year, we can take a look.

Your next question comes from the line of Ramakanth Swayampakula from H.C. Wainwright.

This is RK from H.C. Wainwright. A lot of my questions have been answered, but I have a couple of them. On the OCU400, where you're planning for -- to start the rolling BLA in third quarter, can you confirm your PPQ runs would be completed in time, like by end of second quarter or so, so that you can initiate your rolling BLA?

Yes, absolutely. We're on target to complete them this quarter. And can support the prelim submission.

Okay. Great. Rita, in terms of expenses, we have seen G&A and R&D expenses go up this quarter, which is understandable. But how should we think about this going forward, especially into 2027 as you're preparing for commercialization? And relatedly, on the BD side of things, what progress has been made, especially for 400 and 410 in terms of ex-U.S. licensing?

Yes. Thank you for your questions. So first of all, just to kind of address the spend that you're seeing, you have to consider, part of it is due to timing and then also related to us exceeding some of our programmatic milestones, right? So if you're looking at OCU410ST and OCU410 GA, we accelerated those timelines. And so when you think about us completing our enrolment for OCU400 and OCU410ST, the completion of that enrolment in Q1 will now enable us to kind of ramp down the clinical spend going into the balance of the year. So we feel really confidently about the anticipated spend that we had in 2026 going into 2027. And so we're averaging around $50 million to $60 million per year from a spend perspective, which is why we believe that our cash runway is into 2028.

And then going to the business development, we are actively evaluating various BD deals for ex-U.S. for both OCU400 and OCU410ST. We have term sheets that we're looking at. So there's a lot of work going on just as Shankar said, that Abhi is doing, who leads our business development team, to ensure that we are evaluating those alternatives and then making the best decision for Ocugen and for our shareholders.

And then lastly, from a commercialization perspective for OCU410GA, we are still looking to commercialize that with a partner, although as we talked about the spend associated with the clinical trials, we have that incorporated into our runway.

One last question. Shankar, I know in the past, we have talked a little bit about payers and how to get payers agree to the pricing that you would come up with. Any commentary, especially from recent conversations from your payers as you're getting closer to commercialization, especially with the price tag that you are thinking for some of your drugs?

Yes. I mean, obviously, we -- there is a publication in Retina, I mean, that talks about potential pharmacoeconomic model justifying $1 million to $2 million, somewhere in the range price tag. And also, there is a publication from New England Journal of Medicine. And this is, again, we're happy to state CMS and CMMI, they're looking into what is the next iteration of sickle cell model they created. And the publication clearly goes into pay-over-time and subscription models, which can help with the budgetary constraints we have, how can we work. So everything is very creative, RK, as I mentioned before, from launch and the treatment centers to and how the CMMI is looking.

I'm very pleased to say it's obviously, these are onetime treatments, right? So we need to think about some creative ways, how can we work with payers and make sure, especially if CMS the government is spending a lot of money for orphan diseases or diseases like GA, which will have -- most of the patients are above 60, and you're going to get a bigger chunk of economy and the budget from CMS. So we need to really think into all those options, how we can provide market access to more patients and who need them. And then are there -- so that immediate article coming out of CMS is a good one. And it goes into, okay, if the price tag is high, you pay our time. Because if you say your therapy is onetime treatment for life, you stand by it. And so those are very good models coming out. I mean it's a very creative thinking, and we are aligned with that strategy.

Your next question comes from the line of Daniil Gataulin from Chardan.

I have a more general question on EZ preservation. It appears to be emerging as an important endpoint. So I wanted to ask in your conversations with regulators, what would you say their most recent position is on the importance of EZ preservation? And two, are there any differences in how U.S. and EU regulators are thinking about EZ preservation?

Daniel, good question. We just submitted our meeting request to both FDA and EMA. Obviously, I will let you know by early third quarter, the input and alignment with them. I mean, obviously, you saw GA trial, what we publicly stated. Our primary endpoint is lesion because that's an approved endpoint into commercial products in the U.S. And the secondary endpoint is we are proposing is ellipsoid zone because it correlates to visual function. We believe that should satisfy them, EU regulators. And obviously, we're going to wait until we complete all the meetings, everything buttoned up and aligned, then we'll let the markets know.

That will conclude our question-and-answer session. Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

Good morning, and welcome to Ocugen's Webcast to discuss the Top Line 12-month Results from Phase II ArMaDa Clinical Trial Evaluating OCU410 for Geographic Atrophy or GA Secondary to Dry Age-related Macular Degeneration.

Please note that this call is being recorded. [Operator Instructions]

I would now like to turn the call to Tiffany Hamilton, Ocugen's Head of Corporate Communications. Please go ahead.

Hello, everyone. Joining us today are Dr. Shankar Musunuri, Chairman, Chief Executive Officer and Co-Founder of Ocugen; Dr. Huma Qamar, Chief Medical Officer of Ocugen and our distinguished clinical investigators: Dr. Lejla Vajzovic, MD, FASRS, Professor of Ophthalmology, CME Program Director, Duke Ophthalmology, Duke University School of Medicine and Chair, Ocugen Scientific Advisory Board; Dr. Jay Chhablani, MD, Professor, University of Pittsburgh and UPMC Vision Institute and President of NetraMind.

We are also pleased to be joined for the Q&A by clinical investigators and the Ocugen management team. Clinical investigators include Dr. Victor Gonzalez, MD, Retinal Surgeon, Valley Retina Institute, McAllen, Texas, Faculty at University of Texas Rio Grande Valley; and Dr. Syed Shah, MD, Vice Chair for Research and Digital Medicine, Director of Retina Service, Department of Ophthalmology at Emplfiy Health, La Crosse, Wisconsin, and Ibn al-Haytham Professor, Department of Ophthalmology, Aga Khan University; and finally, Dr. Arun Upadhyay, PhD, Chief Scientific Officer, Ocugen.

A replay of this webcast, along with the accompanying slide presentation will be available on the Ocugen website after the event.

I'll now turn the call over to Dr. Shankar Musunuri.

Thank you, and good morning, everyone. Today, we are pleased to share top line 12-month data from the Phase II ArMaDa trial of OCU410 in GA, an advanced form of dry age-related macular degeneration. These results mark an important milestone for Ocugen as we advance a potential first-in-class modifier gene therapy designed as a onetime treatment for patients with GA.

Here are our forward-looking statements. We have organized today's webcast to provide a comprehensive view of the program. I will begin with a brief overview of Ocugen's mission and the unmet medical need in GA. Dr. Huma Qamar will review the clinical design, safety and tolerability profile. Dr. Lejla Vajzovic and Dr. Jay Chhablani will then review the Phase II ArMaDa trial top line 12-month efficacy results. We will then move into the Q&A with clinical investigators, Dr. Victor Gonzalez and Dr. Syed Shah and Ocugen Scientific Officer, Dr. Arun Upadhyay, followed by closing remarks on OCU410 upcoming milestones.

Ocugen is focused on transforming the treatment of serious eye diseases through innovative gene therapies. Leading ophthalmic gene therapy treatments, our goal is to address major causes of blindness with potential onetime modified gene therapies that target the underlying biology rather than simply slowing a single pathway.

In GA specifically, patients today face a lifelong burden of frequent intravitreal injections with therapies that act only on the complement system. Our vision with OCU410 is different, a single subretinal administration designed to modulate multiple disease relevant pathways and provide durable protection of retinal structure and function.

To set the stage for the Phase II data, let me briefly review the GA patient clinical representation and OCU410's mechanism. OCU410 is built on a novel mechanism of action that we believe has the potential to disrupt the current treatment paradigm in GA. Today, patients with GA face a progressive, irreversible, loss of retinal tissue that ultimately affects central vision. And this can translate into difficulties at reading, recognizing faces and performing everyday tasks.

Once GA develops, the disease continues to progress and the vision loss cannot be recovered. There are an estimated 2 million to 3 million patients with GA in the United States and Europe. Importantly, this number is expected to increase significantly as populations age. Currently approved treatments target only the complement pathway and require 6 to 12 injections per year indefinitely, leading to substantial burden and significant dropout rates in real-world practice.

There remains a clear need for a differentiated therapy that addresses all key disease pathways, including complement, inflammation, oxidative stress and lipid dysregulation, while reducing treatment burden. OCU410 through RORA modulation was specifically designed to address that need. It is a modifier gene therapy that potentially delivers the RORA gene using an AAV5 vector that targets retinal pigment epithelium and photoreceptor cells using a single subretinal injection. This multi-pathway profile distinguishes OCU410 from complement-only inhibitors that are on market today and provides a strong biologic rationale for the clinical effects where you see.

The Phase II ArMaDa data demonstrates that OCU410 may offer meaningful advantages over currently approved therapies for GA. First, OCU410 is designed as a potential one-and-done subretinal gene therapy. In contrast to the 6 to 12 intravitreal injections per year required with the current standard of care complement inhibitors. Real-world data already shows up to 40% dropout rates with the current intravitreal therapies, highlighting the impact of injection burden and treatment fatigue on long-term events.

In our model trial, we observed promising data in both Phase I and Phase II, including suggested structural preservation at the level of the GA lesion and preservation of the ellipsoid zone, which correlates with visual function. Importantly, the safety and tolerability profile has been favorable to date with no serious adverse events or adverse events of special interest deemed related to OCU410.

On this slide, you will see a comparison of mean change in GA area from baseline relative to natural history reported for lesion growth in published data from OAKS and DERBY and GATHER2 studies. OCU410 shows a 31% reduction in lesion growth versus natural history compared with 15% and 19% reductions reported for currently approved therapies, respectively, and a 31% reduction in our treated group versus control with the ArMaDa study. These findings underscore the potential of OCU410 to deliver robust lesion control with a single administration and redefine the landscape of GA treatment globally.

I'll now hand it over to Dr. Huma Qamar to discuss the Phase II study, clinical design and study results. Huma?

Thank you, Shankar. The Phase II ArMaDa trial was designed to evaluate the safety and efficacy of OCU410 in patients with GA secondary to dry AMD. We enrolled a subject 50 years and older with GA lesions within the foveal or non-foveal region, a total GA area between 2 and 20.5 millimeter square, corresponding to approximately 1 to 8 disc areas and a baseline BCVA of at least 21 ETDRS letters.

Patients were randomized 1:1:1 to receive a single subretinal administration of OCU410 at a median dose of 1 into 10 raise to power 10 vector genomes per eye, a high dose of 3 into 10 raise to power 10 vector genomes per eye or no treatment in the control group.

Each injection volume was 200 microliters. Of note, choroidal neovascularization in the fellow eye was not exclusionary and patients with prior exposure to pegcetacoplan or avacincaptad pegol were eligible following a 3-month washout. The primary endpoint was change in GA lesion size at 12 months measured in square millimeters by fundus autofluorescence, an FDA-accepted structural endpoint used in recent GA registration trials. Exploratory endpoints included ellipsoid zone for EZ preservation on OCT, a key biomarker for photoreceptor integrity, which correlates with visual function.

Let me now show you who we enrolled, and how well the groups were balanced at baseline. Starting with the table on the left, this slide summarizes baseline characteristics for the medium dose, high dose and control groups. All participants were older adults with mean ages of about 75 years of age in the medium dose arm, 78 years of age in the high-dose arm and 77 years of age in the control arm. Patients ranging from 62 to 88 years of age were enrolled in this trial.

Mean baseline GA lesion size was roughly 8 to 9 millimeter square and the corresponding squared to transform lesion size was about 2.8 to 2.9 millimeter, consistent with lesion sizes enrolled in pivotal trials for currently approved therapies. Foveal and non-foveal lesion involvement was broadly similar between arms and most patients were pseudophakic, reflecting typical real-world GA demographics.

Base BCVA averaged around 57 ETDRS letters in both OCU410 dose groups and approximately 47 letters in the control group with a mix of unifocal and multifocal lesions.

Overall, these well-balanced baseline characteristics support the interpretation that subsequent differences between arms are more likely related to treatment effects than to initial imbalances.

Turning to the clinical trial flow on the right, 51 subjects were dosed and allocated approximately equally to control, medium dose and high dose groups. In the control arm, 17 subjects were enrolled with 4 later categorized as lost to follow-up in the medium dose arm, 17 were enrolled with one lost to follow-up. In the high-dose arm, 17 subjects were enrolled, 1 experienced a serious adverse event assessed as unrelated to OCU410 and two additional subjects were excluded from the efficacy population, 1 for not meeting lesion criteria and 1 due to an inevaluable GA lesion.

After these exclusions, 45 subjects contributed to the overall safety population. Of these 42 met the primary overall efficacy criteria based on prespecified lesion size thresholds forming the main efficacy analysis set. A modified intent-to-treat population of 39 subjects used slightly narrower lesion size boundaries for more robust analysis and the same lesion size criteria were used for approved clinical trials.

Finally, 31 subjects met the potential Phase III intent-to-treat criteria defined by higher baseline lesion sizes, providing an early look at how the therapy may perform in a population aligned with anticipated Phase III eligibility.

For context, Phase I was a dose-ranging dose escalation portion of the OCU410 clinical trial designed to identify a safe and biologically active dose range. We established the maximum tolerated dose in Phase I.

Phase II builds on the clinical profile observed in Phase I. Across 45 subjects, there were no serious adverse events and no adverse events of special interest deemed related to OCU410. We closely monitored adverse events, serious adverse events and adverse events of special interest, including endophthalmitis, retinal detachment, retinal vasculitis and vascular occlusion, choroidal neovascularization, intraocular inflammation, ischemic optic neuropathy and treatment-emergent serious or serious adverse events.

In both the medium dose and high-dose OCU410 group, there were no treatment-related serious adverse events or no treatment-related adverse events of special interest reported today. 1 case of mild intraocular inflammation was reported in the high-dose cohort and was deemed related to the surgical procedure and resolved with standard management of care.

CNV events reported as adverse events were assessed by the Independent Data and Safety Monitoring Board and related to natural history of the disease and study procedure. Overall, these findings support a favorable safety and tolerability profile for a onetime subretinal gene therapy in this older GA population.

I'll now turn it back to Dr. Lejla Vajzovic and Dr. Jay Chhablani to review the efficacy data.

Thank you, Huma. This slide summarizes the magnitude of treatment benefit we see with OCU410 at 12 months. On the left, you can see the overall analysis for all evaluated eyes with baseline lesion area between 2 and 20.5 millimeter square. The red bar represents the control group and the orange bar shows all OCU410 treated eyes combining the medium and high doses. At 12 months, treated eyes have smaller increase in geographic atrophy lesion area compared to the control and corresponding to the overall 80% reduction in lesion growth versus control.

The middle panel narrows in on lesions between 2.5 and 17.5 millimeter squares, which is, as mentioned earlier, is the criteria that captures the majority of patients in both ArMaDa and the prior pivotal GA trials that supported the approval of currently available therapies. Here, we separate out medium dose in green and high dose in blue with natural history and control bars for the contacts. In this range, the medium dose group shows about 31% reduction in lesion growth versus control and the high dose group shows about 16% reduction at 12 months using mean change in the GA lesion area from baseline.

For context, the gray box highlights that currently approved products typically demonstrate roughly 15% to 22% lesion growth reduction. OCU410 is delivering approximately 2x greater anatomic benefit in half the time after a single treatment.

On the right, we focus on subgroup with a baseline lesion between 5 and 17.5 millimeter square, an interval that includes most evaluated subjects in ArMaDa and in other contemporary geographic atrophy programs. This is where the treatment effect becomes even more pronounced. In this subset, OCU410 at the median dose achieves 33% reduction in lesion growth versus control at 12 months, and the high dose shows 31% reduction against the mean change in the GA lesion area, millimeter square from baseline to month 12.

Now taken together across overall population and establishing within this 5 to 17.5 millimeter square window, a single subretinal administration of OCU410 consistently shows GA progression versus control. Most patients in currently GA trials fall within this range, which provides a strong evidence that base for our planned Phase III inclusion criteria.

In summary, this data demonstrated efficacy of OCU410 across multiple doses levels. However, medium dose was observed to be optimal dose for GA patients across wider demographics. This dose will be selected for further clinical development in pivotal Phase III confirmatory trial.

I will now hand it over to Dr. Jay Chhablani.

Thank you, Lejla. Here, you can see the efficacy results from Phase II demonstrate a consistent treatment benefit on both structure and a structure parameter that correlates with visual function.

On the left side of this slide, you see the primary endpoint that is change from baseline in GA lesion area at month 12. In the medium dose OCU410 group, we observed a statistically significant reduction that is p less than 0.05 in lesion growth that is 31% compared to control using mean change in the GA lesion area from baseline to month 12.

On the right, you see the exploratory endpoint of ellipsoid zone area loss, which correlates with the photoreceptor integrity and visual function. The EZ represents the inner segment, outer segment junction of photoreceptors as visualized on spectral domain OCT imaging. This is a critical anatomical marker of photoreceptor health and integrity. Loss of ellipsoid zone indicates photoreceptor degeneration and death.

Preservation of the ellipsoid zone indicates maintained photoreceptor structure and by extension, likely maintain or improved photoreceptor function. Here, treated eyes showed a 27% slower rate of EZ loss compared to control, indicating preservation at the level of the outer retina, which correlates to visual function. These findings are consistent with OCU410's mechanism of action and our preclinical findings regarding RORA's neuroprotective and antioxidative mechanisms, providing clinical evidence that OCU410 can preserve photoreceptor structure in GA patients.

The ability to protect both photoreceptors and RPE with a single therapeutic intervention underscores the advantage of our multi-pathway targeting approach. We are not just addressing one aspect of GA pathogenesis, we are supporting the health and survival of the entire photoreceptor RP unit.

In conclusion, medium dose not only showed effect on GA lesion growth reduction, but also demonstrated preservation of EZ layer, which correlates with visual function. Based on this data, medium dose will be chosen as an optimal dose for Phase III confirmatory trial.

I will now hand it over to Lejla.

Thank you, Jay. Another way to look at treatment benefit is through responder analysis based on different reduction thresholds in GA lesion growth.

On this slide, we show the proportion of treated patients who achieved at least 10% to 50% reduction in lesion growth compared to controls and natural history. More than half of the subjects treated, specifically 55% achieved a reduction of at least 30%.

The median reduction across treated subjects was approximately 33%. Responder rates at these thresholds were statistically superior to natural history. These partner data underscores the robustness of treatment effect at the individual patient level and support the potential for OCU410 to deliver meaningful clinically relevant slowing of GA progression.

I will now ask Shankar to walk you through the next slide.

Thank you, Lejla. As you have seen, we believe OCU410 has the potential to create a new standard of care for patients with GA. It is a first-in-class RORA-based gene therapy designed to support central retina and photoreceptor integrity through a multi-pathway mechanism targeting drusen, inflammation, oxidative stress and complement activation.

The Phase II ArMaDa results demonstrate a compelling efficacy profile, including a 31% reduction in GA lesion growth and a 27% slowing of ellipsoid zone loss alongside a favorable safety and tolerability profile. By offering a onetime treatment, OCU410 has the potential to eliminate the chronic treatment burden associated with monthly or every other month intravitreal injections and to reduce treatment attrition driven by patient fatigue. We are incorporating these learnings into an optimized Phase III trial design, including a targeted GA lesion size window for vision preservation and an adaptive design powered at 95% with approximately 300 patients globally.

We are targeting initiation of the global Phase III program in the third quarter of 2026, subject to regulatory alignment, and we look forward to working with the investigators and broader retina community as we move OCU410 into late-stage development.

You have now heard the key elements of Phase II ArMaDa trial data, a favorable safety profile, robust structural and mechanistic signals and clear rationale for dose selection and Phase III design. To round out the discussion, we have asked our investigators to share their perspectives on what these results mean in the context of current clinical practice.

Now we will open the line for Q&A.

Your first question comes from the line of Robert LeBoyer of NOBLE Capital.

Congratulations on this data, Arun's magnificent data, the ArMaDa trial. I knew it all along. But my question has to do with the patient population and the patients that would be candidates for the treatment. The patient population is very large. And I was wondering which patients would be selected and if there was a target or would it be all GA patients? Would you wait until the AMD progresses to the point where you have GA, or would you treat earlier? Just -- I was wondering if you could give some perspective on how this would be used in practice after approval.

This is Huma Qamar. Thank you for your question. So in terms of Phase III, this will be, first of all, global trial, and we will be having geographic atrophy. That's the clinical presentation of geographic atrophy secondary to dry age-related macular degeneration.

Of course, the most important criteria is around the diagnosis of 50 years of age and older. And it also depends on the clinical signs and symptoms. So that would be all comers who are presenting with the geographic atrophy with the foveal and non-foveal lesions. And at that time, we will have a prespecified criteria on the lesion size, and that would be something that would be unique to this Phase III trial that we are looking into in the future.

Okay. And can you give the expected enrollment criteria -- more the enrollment size of the Phase III?

Yes. So as we have stated that there will be approximately 300 patients globally, and we will have a unique adaptive design, which will be powered -- the trial will be powered at 95%.

Your next question comes from the line of Michael Okunewitch of Maxim Group.

Congrats on the really great-looking data here.

Thank you. Thank you, Michael. Go ahead.

Just to start things off, there seems to be quite a difference in performance, in particular, for the high-dose group when you exclude those patients with less than the 5-millimeter squared lesion size. So could you provide a bit of color on why this might be -- what might be more challenging about those patients with the smaller lesions?

Yes, I think it has more to do with the few outlier in the high dose group, I would say. So if you look at cutoff criteria, we are talking about with more than 5 and less than 17.5. So few outlier patients in the high-dose group testing were basically impacting the data readout. But on top of it, there are also like confounding factors related to some of the patients' medical history.

And as well as if you look at our preclinical published data, I think purpose of this whole Phase II study was to understand and find the optimal dose. In preclinical study, we also noted that medium dose was kind of optimal dose and this molecule does demonstrated bell-shaped like curve for dose response. So if you take everything together, it appears that medium dose is optimal dose for the GA patients. High dose may be slight towards tapering end and the few outlier and confounding factor taken together may have led to the lower -- slightly lower efficacy in high-dose group compared to the medium dose group. That's our analysis.

I appreciate the additional color. And then just one more for me, and I'll hop back into the queue. So I think it's pretty obvious what the patient benefit here is for a onetime therapeutic. But have you had any feedback from KOLs that you might need to clear a higher bar for efficacy or long-term safety to make them comfortable given just how novel the modifier gene therapy modality is?

So I'll take this question, and thank you for the question. So in terms of safety, I will say that the safety and tolerability profile of these patients was very favorable. We have, if you look at it, the lower limit was in 60s for this patient and the higher limit was 88 years with comorbidity. So we have not seen any adverse events or serious adverse events or adverse events of special interest.

Also in terms of -- I'm not concerned about the safety and tolerability profile at all because the Phase I was the dose-ranging dose escalation portion of the study where we established the maximum tolerable dose. And also from efficacy, if you look at it, we have foveal and non-foveal lesions. And majority of the efficacy was coming from like the aggressive lesions as well. So this is not only from a safety perspective and tolerability perspective, but also from efficacy, we address those concerns. And I don't think so we have any concerns regarding moving forward in terms of the safety and tolerability database for these GA patients.

One more thing I would like to add, and I would like to acknowledge our surgeon, Dr. Lejla Vajzovic and all the other investigators as well. We have a very standardized surgical manual and procedures. We have a standardized volume. We have a standardized dose. So what we were giving in the medium and high dose, in fact, when we did look at that, there were no adverse events or serious adverse events as well. So we have also added very standardized surgical procedures. We will be following the same across -- this has been across all our gene therapy programs, and we are very confident that there will be no safety or tolerability issues moving forward.

Michael, just to -- in addition to Huma's comments, very nicely put it together. I'd like to add. There is a significant unmet medical need across the globe for this disease. Remember that. And when we are showing a treatment benefit within a year, I mean, obviously, agencies will work with us, that's the anticipation, they're not going to extend.

And the safety perspective, all our clinical trials for gene therapies, FDA mandates, even it's a 1 year needed for, let's say, pivotal trial for registration trial, we have to monitor the patients for 5 years. That means just like we did with the OCU400 other programs, by the time we file for our potential approval BLA in 2028, if everything goes according to the plan, we will have at least 3 years of data from Phase I and data from Phase II, and that will be supporting the safety of the molecule.

Michael, if I may add.

Yes, go ahead, please. Go ahead.

Thank you. This is Lejla Vajzovic. Thank you for that question. From kind of providing clinician perspective, I'm excited to see overall positive results as early as 1 year in overall, what I would say, a small group of patients. Yes, this is a very robust trial for gene therapy in Phase II.

Geographic atrophy is a heterogeneous disease with really various progression rates that we see among patients. And I think that's the biggest challenge we have currently with geographic atrophy in general. But to see this diverse patient population that were included in this trial to see actually positive results in both doses is encouraging to me. It's excited to see the medium dose did better than higher. But overall, I'm encouraged to see early positive results at 1 year.

This is Victor Gonzalez. May I make a comment? That's a great question.

Yes. Yes. Go ahead.

I mean I think -- as someone in the trenches taking care of these patients, the excitement aside from all the great results that you had presented here is the fact that it meets one of the biggest concerns and issues that I have, and that's the treatment burden on these patients. I cannot give the treatment benefit to these patients as the patients don't show up for the current application of medications.

The fact that I can take care of these patients, give them the treatment once and have the benefit over that year is going to address the biggest concern that's happening out there. There's a 40-plus percent dropout on these patients because they get burned out from having to require these recurrent treatments. The ability to do this with a one-and-done treatment like this one is going to address that big unmet need, and that is getting the treatment effect, getting the medication to these patients. So thank you for your question.

I appreciate all the additional commentary. I'm looking forward to seeing more data come out from this program and the others.

Your next question comes from the line of Leland Gershell of Oppenheimer.

Great to see these data. A couple from us. First, just a question from -- really directed at the specialists who joined the call. The data clearly supports OCU410's potential in GA and could have considerable market opportunity given the number of patients with this disorder.

But I wanted to ask, given the subretinal injection versus the intravitreal, which are how they're currently approved treatments are delivered, I want to ask kind of how you see the pace of adoption given the need for maybe training for subretinal injections? Do you think that patients would be referred to specialists and centers who have expertise in that? Or do you think that the ability to give those injections will expand as this drug becomes available. Again, given the much larger size of this population versus the other two opportunities that the company is going after? And then I also want to ask the company, what's your plan for continuing to follow these patients beyond 12 months? And when might we see an incremental follow-up?

So I would, first of all, direct the question to either Lejla, Dr. Shah or Victor. Any of you guys can answer that. That's first. And the second part, I will answer later on.

Thank you, Huma. Happy to take on the question regarding surgical approach versus intravitreal injection and benefits related to that.

Now yes, intravitreal approach is something we're routinely doing and quite commonly retina specialists in doing quite a few injections throughout the week for patients. So we are very comfortable and obviously, it's in-office procedure approach. Now it has been mentioned that with current therapies, repeating injections once a month to every other month definitely presents its challenges with follow-up rates and just keeping up with that treatment burden is definitely troublesome.

When it comes to developing a onetime approach surgically, yes, any surgery comes always with the risks. I think in this day and age, there has been across Ocugen and other programs, quite a few investigations and potentially approved products in the near future that will very much give us this option of gene therapy delivery in common retinal diseases.

And through all of these programs across all the companies, we now have more than hundreds of clinical surgeons involved in U.S. and globally that have been delivering these therapies through trials for patients and patients from all the reports we're getting are doing quite well. So to answer your question, the challenge was this going to be a specialty referral to a surgeon who's just going to be doing that.

I think I believe the answer to that will be, no. I think any retina specialists will feel comfortable doing this procedure. I think more the logistics would be whether that therapy would be available at that hospital they're performing the surgery at. But the surgical steps are very, I would say, at this stage, routine for all of us and then adding the gene therapy product is not that complicated of a process.

Yes. This is Dr. Shah. I would like to add as well. Given I have a large encashment area of rural America or Wisconsin for that matter, I cannot tell you how many patients when they come in with GA and you offer them the standard of care, and they just back out because traveling for them from half an hour, 1 hour, 2 hours away, having somebody drive them because they cannot drive themselves is a big challenge.

And if you have something like this, which is one-and-done treatment, I think there will be so many patients just in this rural encashment area, I treat would be very amenable to treatment even if its subretinal injection. And this is across the board to all injections. People do not like monthly, every other month injections because that's just the patient who has to come in.

Remember, these patients cannot see very well. So they have to have someone in their family take off and bring them in, and that's a whole day gone for them. And if you offer them something, and they actually ask that, is there anything else you can give me, which is once or twice a year or something like that, how many patients -- there are plenty of patients like this. So I think enrollment and adoption of treatment, which is less burdensome than what we have right now will be a great thing for our patients.

This is Victor Gonzalez. Just to make a comment to you. I'll tell you, I'm going to date myself, but this was exactly the same question that we had when we first started doing intravitreal injections. Everybody first was horrified to think that we would be doing that and will the patients really come back. And I think the retina community, noticing the benefits that were created was able to adapt this.

And as Lejla and everyone has mentioned, there is a learning curve. But I think the environment is such that there are so many of these subretinal options coming that it will become similar to an intravitreal injection, people will adopt it, and there will be the training that's necessary to be able to deliver these new therapies.

Your next question comes from the line of Swayampakula Ramakanth of H.C. Wainwright.

This is RK from H.C. Wainwright. It's obviously great data. So a couple of quick questions from me. One on the data and one, just a high-level thought. On the data itself, regarding the EZ -- the method by which the EZ was measured -- EZ preservation was measured. You have a competitor who says in the central 1.5 millimeters, they have a 59% preservation of the EZ region. And when we compare that against your 27%. So how do we think about that? Is that because you're looking at the entire macula, or you're looking at a certain subfield?

So I will direct that question to Jay. Jay, would you like to take that question?

Yes. Thank you. Thank you so much. Very interesting question. And I think that I would say the jury is still out that which area on the GA pretty much defines the vision. And I would rather be more interested to understand that which area on the -- of the GA in the macular region pretty much defines the functional vision.

So I think that the central 1 millimeter definitely plays an important role. But so far, we haven't done the zonal analysis for this data. Whatever -- because I was primarily involved in the EZ analysis of this data. So -- what I -- what we learned, which we could not share in this data set now is that because of time limitation, the patients who did not have foveal involvement, they actually had a significant benefit of both EZ preservation and hopefully corresponding to their functional vision as we believe that EZ could relate with the functional vision.

So we will be able to share more information on the central and the paracentral area. But EZ is certainly something becoming a very important anatomical biomarker, which corresponds with the functional benefit.

And then the next question is just trying to understand the benefits of this therapy and time, right? So what am I saying? If you consider the sizes of the lesion, it looks like the smaller lesion sizes did not get as much benefit as the medium to large-sized lesions, plus considering the heterogeneity of the disease, and you are only taking a 12-month time point here.

So if we get to see additional time points, would this track -- would this treatment track to better benefit either depending on the size of the lesion or the time spent on the disease or the time point that you're looking at? I'm just trying to understand how as the disease progresses, does the benefit get better?

RK, I'll take that. And if anyone has additional comments, they can chime in. So in terms of your question about the lesions. First of all, we had all foveal and non-foveal. Our criteria was around 2.5 to 20.5. We have demonstrated different graphs. And the reason for that was if you look at it as a bifurcation between 5 and 17.5 as well as because the mean lesion size and all the approved pivotal trials was between 7.0 to 8.23.

And we also looked at the smaller lesions as well. However, we had 2 doses that we're looking into it. And the optimal dose is the one that performed regardless of the lesion size across all groups. And of course, the purpose of those double grafts, triple grafts was to show various scenarios and pictures in terms of lesion size and also the dose response to that. So we have addressed that. And the purpose of this trial was also to find the optimal dose, which we did it, and that's what we anticipated that we will have one optimal dose, and that's what we picked up. In terms of the 12 months, that's the standard duration of the trial, and that's what we have done here.

Yes. In addition, RK, I mean, we'll always monitor patients. We have obligation with FDA and agencies. And also ethically, we would like to continue to monitor patients. Typically, all gene therapy trials for 5 years, as I mentioned before. That means the Phase II data, we got 1-year data now. We'll continue to monitor by '28, 3 years. As we monitor them for 3-year, second year, third year follow-ups, the data will be available at the time of submission. So you will have some durability data from early-stage clinical trials with the BLA.

Your next question comes from the line of Elemer Piros of Lucid Capital Markets.

Shankar, just to reiterate your last comment. So you would have efficacy measures taken at 24 months, 36 months, et cetera. Is that correct?

Yes. As part of the safety, we'll be monitoring patients, yes, key measures. Yes.

Okay. And I'd just like to verify that your Phase III enrollment criteria, would it be narrowed down to the 2.5 to 17.5 square millimeter baseline size?

Yes, yes, yes. And the efficacy measures will also be included in the follow-up. That is correct. The patients will be coming not only for safety, but of course, their examination will include the efficacy parameters.

Your next question comes from...

I would like to add one thing. So even though you run the trial like even for currently approved therapy between 2.5 to 17.5. However, like in a clinical practice, every GA patients get the treatment. So it doesn't put any restriction on the label. Label doesn't -- to carry...

That's right.

Your next question comes from the line of Daniil Gataulin of Chardan Capital.

Congrats on those data. A few questions from me. First, on the dose response. Do you think it was driven primarily by a couple of outliers, or is there another hypothesis why medium dose performed better than the high dose?

Daniil, this is Arun. There are two aspects. Definitely, outlier did contribute to it. But in addition to that, we also believe that the pharmacological response, what I just mentioned briefly, that bell-shaped dose response curve. So in our preclinical study also, we noted that certain dose were optimal dose where we saw the maximum benefit.

And if you go across both, lower or higher end of that dose, then you see some drop in the overall efficacy. So maybe in this clinical setting, whatever lower response we are seeing for high dose group, it is not just attributed solely to outliers. Yes, they are major driver. But on top of it, the pharmacological dose response curve has also contributed to that lower efficacy.

Okay. Got you. Okay. My other question is with respect to vision. Did you collect BCVA data? And do you anticipate sharing those results?

So Daniil, this is Huma. So yes, we did collect the visual acuity. And as you know, with this population, we -- and with the LLVA, it's going to be like it takes 18 to 24 to 36 months to show the maximum benefit. The BCVA was within any single subretinal injection is kind of like 15 to 20 days and also up to 3 to 4 months can be fluctuating.

However, LLVA, as we have seen and consistently demonstrated in our previous gene therapy trials as well, the durability happens around 24 months and more. So that is why we have an ellipsoid zone analysis, which is structural and anatomical factor or biomarker, which is correlating, as Jay has rightly said, with visual function.

Got it. Makes sense. And my last question is you mentioned that the inclusion criteria are open to patients who have previously taken complement inhibitors. What fractions of those patients were in your trial? And did they perform any different?

Yes. So we did have a 3-month washout period with the approved therapies and approximately 10% to 12% of the population was that.

Okay. And did they have any different results versus those who are naive?

Their safety was outstanding, and those are also part of the analysis here, the efficacy analysis, they contributed. And CNV was also not exclusionary in the fellow eye. So that's good that even naive or patients who have taken complement or any other approved therapies have contributed to the efficacy profile here.

Our final question comes from the line of Whitney Ijem of Canaccord.

This is Angela Qian on for Whitney. So we realize it's currently relatively small numbers here, but is there anything in terms of baseline characteristics that you've been seeing in the better responders that might help enable you to enrich a pivotal population?

So yes, it is a small population. But actually, if you look at the inclusion/exclusion criteria of this trial, this was approved consistent with the approved therapies as well. And in terms of the baseline characteristics, we do not see any differences, and this is what we have represented here.

Whitney, I think just to clarify, I mean, again, we cannot compare the population in genetic medicine trials with other therapies, other modalities with many products which got approvals in 30 to 35 patients. So typically, when you see something in gene therapies, you can go back and look at the data, the trends continue. And so even the small population gives robust responses, and that will continue, and you'll see it in the larger population too.

Got it. And then to clarify, are we correct to think that you're using the high dose in the Stargardt trial? And if so, what was the rationale there?

No, we are not using high dose in Stargardt. We have for pivotal study, we have chosen the dose between medium and high dose. And it is a different indication. So if you look at our Phase I Stargardt trial, the dose levels are different in that study compared to the dose levels in the GA because they are 2 different ages, okay? So no, they are not similar. They're slightly different approach.

And I can add that as well because we have a pediatric population in the Phase II/III and Stargardt is primarily the disease of the pediatric population as well. So we have chosen between the medium and the high dose with a standardized volume.

Got it. Okay. And then maybe the last one on the Stargardt, looking ahead to the interim this year, can you just remind us what you expect to share externally?

Yes. So the -- this will be the masked interim analysis for 24 subjects, 16 in the treatment, 8 in the control, but it will be all blinded data. As we have been consistently showing our lesion size reduction data, we have recently shared ellipsoid zone and visual acuity. So it would be somewhat around those parameters that will be available in the midyear.

And Whitney (sic) [ Angela ] I think just to clarify, it's the outcome of the results. Again, how much we can share with the market. As she said, it's still a blinded study. And then the goal is to look at the -- and DMC, the Data Monitoring Committee, output will be discussed with FDA.

And the outcome is important for the trial. Outcome means adaptive design allows us to derisk any risk to the clinical program because you have a true control group, you'll be able to compare. And there are -- what are the potential outcomes? If the predictive analytics show, we're going to get it at 12 months, no change to the trial. That means top line results are going to come out in the second quarter of next year. And following that, we'll file the BLA.

And the second option is, yes, you need to adjust and up. That's an option. FDA also gives us a third option instead of adjusting and sometimes when you have these retinal degenerative diseases, especially orphan diseases. And based on the natural history, you can also extend the last time point instead of 12 months to 16 months. All those options are available to us, and we'll be closely working with FDA before we give any information to the market.

Now we can open our KOLs for any final comments. Victor, Shah, Lejla or Jay, any final comments? You're welcome to say so.

I just want to make one comment. Victor, go ahead. No worries.

I was just going to say, I just want to congratulate you and really excited about having the prospect of this drug. Again, as I mentioned, this address is one of my biggest unmet needs right now, and that's the undertreatment of patients because of the dropout. With the ability to have a safe onetime application of this treatment, I think I can really benefit my patients a lot more than I have currently. Thank you all.

Yes. This is Jay. I just wanted to make a comment and just to congratulate you all for an excellent study and excellent results so far. I would just say and kudos to Ocugen team that they are taking the right step to really bring the outcome measures. I'm very excited about the EZ preservation. So we are really hoping that this will lead to a very useful functional outcome for our patients. And again, this is a single subretinal therapy, which will really take away the burden of monthly injection from our patients, and we look forward to get started with Phase III and eventually the approvals. Congratulations.

Yes. And this is Lejla Vajzovic. I'll add as well. Thank you Ocugen team for leading really exciting program. Similarly, from a physician perspective, I am excited to see these early safety and efficacy results that are quite promising. We definitely need better solutions for our patients and having an option where we can provide it onetime delivery approach looks very promising. So I'm excited about these early results, and thank you for leading such exciting program.

This is Dr. Shah. I would also like to add thank you, everybody, for such a wonderful program. And I can't tell you enough that in the rural areas where there's a huge amount of geographic atrophy population, how beneficial this would be both on the burden as well. And I want to address one more thing, which pertains to delivery of this vector.

We in a small town Wisconsin are able to do it because not just a surgeon, you have to have the ancillary support for the viral vectors and everything. And it's doable in a small town. So I think it's doable everywhere in the U.S., especially in small towns where there's large encashment area living around that, which will really benefit from it and looking forward to more results. Thank you so much, everybody.

Thank you all, our speakers and panelists and everyone who joined us today. We have confirmed robust treatment effect from a well-controlled Phase II trial for the genetic medicine for GA. Now we can move on to Phase III with a high degree of confidence. This moves us one step closer to bringing transformative onetime treatments to GA patients globally who are desperately seeking rescue from vision loss. Thank you again. Have a great day.

Thank you for attending today's call. You may now disconnect. Goodbye.

Good morning, and welcome to Ocugen's Fourth Quarter and Full Year 2025 Financial Results and Business Update [Operator Instructions] I will now turn the call over to Tiffany Hamilton, Ocugen's Head of Corporate Communications. You may begin.

Thank you, operator, and good morning, everyone. Joining me on today's call and webcast is Dr. Shankar Musunuri, Ocugen's Chairman, CEO and Co-Founder, who will provide a business update and his overview of our clinical and operational progress; Rita Johnson-Greene, our Chief Financial Officer, is also on the call to provide a financial update for the quarter and full year ended December 31, 2025; Huma Qamar, Chief Medical Officer, will be available to answer questions following the presentation.

This morning, we issued a press release detailing associated business and operational highlights for the fourth quarter and full year 2025. We encourage listeners to review the press release, which is available on our website at ocugen.com. A replay of this call, along with the accompanying slide presentation will be available on the Investors section of the Ocugen website.

Before we begin, please note that certain statements made during today's discussion may be forward-looking in nature, including those related to our clinical development pipeline, regulatory time lines, commercialization strategy and financial information and our anticipated cash runway. These statements reflect management's current expectations and are inherently subject to risks, uncertainties and assumptions that may cause actual outcomes to differ materially from those expressed or implied. We encourage you to review our filings with the Securities and Exchange Commission, including the risk factors detailed therein for a more comprehensive understanding of these potential risks.

Finally, Ocugen's annual report on Form 10-K covering the full year 2025 will be filed today.

I will now turn the call over to Dr. Musunuri.

Thank you, Tiffany, and thank you all for joining us today. I'm pleased to share with an update on what was a transformative year for Ocugen, considerable development across all of our modified gene therapy programs, interim licensing and financing agreements to strengthen our financial position and meaningful appointments to our leadership team made in 2025 a year of real momentum for Ocugen.

We are now poised to leverage upcoming catalysts and advance business as we near the first half or 3 BLA filings. I'm proud of what this team has accomplished, and I'm confident that with a full bench of experienced leadership across the organization. We have the resources and the know-how to drive Ocugen's transition into a commercial stage company.

Let me walk you through each program. Starting with OCU400 retinitis pigmentosa, which I will refer to as RP going forward. It is important to note that the Phase III liMeliGhT clinical trial is the only broad RP gene-agnostic trial and the largest known Phase III orphan gene therapy trial, approximately 300,000 people in the U.S. and Europe are living with RP is caused by mutations in more than 100 genes. OCU400 is designed as a modified gene therapy, utilizing MRT, a central transcriptional regulator of retinal-specific pathways to address multiple genetic mutations with a single onetime treatment.

The only approved gene therapy for RP today targets a single zinc RPE65, which accounts for just 1% to 2% of the total RP patient population. We believe OCU400 is significantly wider commercial potential as it is intended to provide a therapeutic option for 98% to 99% of all RP patients.

I'm pleased to report that enrollment is now complete for the OCU400 Phase III liMeliGhT trial as a 1-year clinical trial, top line data will be available in the first quarter of 2027. These data are anticipated to support the biologics license application, BLA, filing for OCU400 and potential approval in 2027. The liMeliGhT clinical enrolled 140 patients for randomized 221 into the treatment group and untreated control group across mutations, including RHO and gene-agnostic arms.

The gene agnostic arm includes many genetic mutations, including those most prevalent. Tulip, Cross, XLRS U.S., HA, XRT and PDA6P. The target population included patients with early to late-stage disease among a broad RP population, including pediatrics. The primary endpoint is 12-month change in visual function assessed by LDMA, luminal dependent navigation assessment with improvement in lux level from baseline to 12 months.

We also released positive long-term 3-year Phase I/II data for OCU400 that builds on or prior to year results. The data demonstrates sustained clinically meaningful approximately 2 line LMA gain, reinforcing durable gene-agnostic benefit. OCU400 maintained a favorable durability, safety and tolerability profile with no new treatment-related serious adverse events or adverse events of interest emerged.

With enrollment complete, and these strong long-term data in hand, we are on track to begin the rolling BLA submission in the third quarter of 2026. Process validation and manufacturing activities are progressing well in support of the time line and brand planning and marketing initiatives are scaling up as well. We anticipate commercialization in 2027 in line with our commitments.

As we prepare for what will ultimately be global rollout to OCU400, we are pursuing reasonable partnerships that preserve Ocugen's right to larger geographies while also generating near-term value for our shareholders.

In 2025, we executed our first regional licensing agreement with Kwangdong Pharmaceutical Co. Ltd. for the exclusive Korean rights OCU400. With offering fees and near development milestone payments, along with royalties, this was a valuable collaboration for Ocugen and a critical step in the company's business development strategy. There are an estimated 7,000 individuals in the Republic of Korea with RP equal to approximately 7% of addressable U.S. RP market. This approach allows us to maximize total patient reach while retaining full commercial rights in the U.S. and Europe.

Now let's move on to our OCU410ST for Stargardt disease. OCU410ST has the potential to target or 1,200 pathogenic mutations in the ABCA4 gene associated with the Stargard disease and other ABCA4 related retinopathies with a single onetime treatment. Stargardt disease affects approximately 100,000 patients in the U.S. and Europe combined and approximately 1 million people globally with no approved treatment options available. The Phase II/III GARDian 3 total complementary trial remains [indiscernible]. We anticipate top line Phase II/III data in the second quarter of 2027, followed by the BLA submission.

In January, we announced a peer-reviewed publication of our Phase I GARDian trial results in nature EYE, which supports a favorable safety, tolerability and efficacy profile of OCU410ST and its potential to provide clinically meaningful functional and structural benefits in Stargard patients. This independent validation, further strengthens the scientific foundation supporting the ongoing pivotal trial.

Importantly, the committee for Medicinal Products for human use, CHMP of the European Medicines agency confirm that data from our single U.S.-based trial can also support an EMA application. This alignment allows us to maintain the same time line and budget efficiencies in Europe as we have with this OCU400 pivotal trial, streamlining our development efforts and bringing OCU410ST to patients in Europe sooner than originally anticipated. The program has also received rare pediatric disease designation, further strengthening its regulatory positioning.

I would like to explain [indiscernible] easy analysis in greater detail as this is now an exploratory end point for both the GARDian III and [indiscernible] clinical trials. The ellipsoid zone is a hyper reflective bank representing photoreceptor inner and outer layer segmentation. It indicates photoreceptor health line and is a biomarker for photoreceptor structural integration and metabolic health easy disruption precedes RPE loss and visible atrophy in geographic atrophy and sartorisease. Easy measurement is important because the progress early and sensitive detection. Easy changes occur to for visible RPE atrophy expansion in GA and Stargardt progression.

It also enables earlier intervention and more sensitive treatment effect detection in GA and Stargardt.

Finally, easy correlates to earlier functional therapeutic benefit with an effect as early as 1 year compared to other measures such as visual acquity with clinically meaningful effect at 2 years or more. Since all of our clinical trials aim to demonstrate benefit at 1 year, and we are targeting significant unmet medical needs, easy is a relevant measure to show functional outcome in these trials. As EZ analysis has been established as a clinically relevant endpoint for dry AMD clinical trials, it was critical to incorporate this measure for both our Stargadt and GHS trials.

As shown in this bar graph, change from baseline at 12 months and treated fellows across doses, excluding 2 subjects lost to follow-up and 1 subject with retinal detachment, demonstrated a mean of 116% in lesion reduction in available treated eyes relative to untreated eye. Specifically, 50% of OCU410ST treated eye achieved easy preservation exceeding expected disease decline at atrophy progression at 12 months. This change from baseline, structural preservation on spectral demand OCT codified as 116% regional reduction and ellipsoid zone integrity highlights meaningful photoreceptor protection and functional therapeutic benefit in Stargardt disease underscoring the key differentiator of modifier gene therapy.

Now let's turn to OCU410 secondary to late-stage Dry AMD. With approximately 2 million to 3 million GA in the U.S. and Europe combined, OCU410 represents a significant market opportunity. OCU410 is basically designed to address multiple pathways implicated in the pathogenesis of tri-agulated macular degeneration and offers a promising advantage over current treatment options, the target only 1 pathway, the complement system.

Currently approved treatment options require frequent intravital injections about 6 to 12 doses per year and are accompanied by various safety risks. For example, roughly 12% of patients developed wet AMD following treatment. There are no treatment approved for GA in Europe and existing FDA approved options have failed to demonstrate meaningful functional outcomes. OCU410 is, therefore, well positioned to address this critical unmet need.

In January, we announced positive preliminary 12-month data from approximately 50% of patients evaluated to date in the Phase II ArMaDa clinical trial evaluating OCU410, the key findings were compelling. We observed a 46% reduction in lesion growth at 12 months across the medium and high dose groups combined versus control with atestical significance at p of 0.05 in a cohort of 23 patients. We also saw a 50% responder rate with patients achieving greater than 50% lesion size reduction versus control.

To put this in context, currently marketed products have demonstrated only a 22% lesion reduction at 2 years. So at 1 year, OCU410 is already delivering more than double the benefit seen with existing therapies at twice the time. The subgroup analysis of patients with baseline GA size of 7.5 millimeter square or greater, representing advanced atrophy demonstrated a 57% reduction in lesion growth in treated eyes for the medium dose and a 56% reduction or the high dose compared with control. This suggests our OCU410 may be even more effective in patients with substantial disease burden.

The data set also included encouraging 12-month Phase I findings where OCU410 treated eye demonstrated 60% slower loss of the ellipsoid zone or EZ compared to untreated fellow eyes. The 60% reduction in EZ loss rate indicates that OCU410 treatment is substantially slowing the rate of photoreceptor degeneration compared to the natural history observed in the untreated fellow eyes. We look forward to reporting the complete data set from OCU410 Phase II ArMaDa trial this month and anticipate initiating Phase III in 2026.

Let me also provide a brief update on our other programs. For OCU200, no serious adverse events or adverse events related to OCU200 have been reported to date across the Phase I dose escalation cohorts and trial enrollment is expected to be completed in the first quarter of 2026. Regarding our MH vaccine candidate, OCU500 NIAID intends to initiate the Phase I clinical trial in the second quarter of 2026.

Finally, we created OptoSelect as a wholly owned subsidiary for our regenerative cell therapy asset, including NeoCart, with the goal to be independent through financing that will maximize value for Ocugen shareholders and patients.

We will provide further details as the process progresses.

Across the portfolio, 2026 represent multiple defined inflection points. These include completion of enrollment for OCU410ST in early 2026, full Phase II data for OCU410 this month, interim pivotal data for OCU410ST in the third quarter, initiation of Phase III for OCU410 in 2026 and start off rolling BLA submission for OCU400 in the third quarter. Each of these milestones build towards longer-term regulatory and commercialization objectives and reinforces our commitment to file 3 BLAs in the next 3 years.

Operationally, we also strengthened our executive leadership team with several appointments, including Abi Gupta to Executive Vice President, Commercial and Business Development, bringing more than 20 years of experience across commercial strategy gene therapy and corporate development in the biopharmaceutical industry. Recently, Rita Johnson-Greene was named Chief Financial Officer. Rita's experience in financial strategy and capital planning supports our continued focus on disciplined resource allocation as our programs advance toward late-stage development and potential commercialization.

And just this week, Paul Steve joined us as Executive Vice President, Operations. Paul has more than 20 years of leadership experience in biologics and cell and gene therapy technical operations. He joins from Bristol-Myers Squibb where for over 16 years, he held leadership roles in manufacturing launch, scale up, orchestration of reliable global supply chains with a quality focus for the last 5 years. He will lead operations to strengthen execution and support the company's transition towards regulatory approvals and commercialization.

I will now turn the call over to Rita Johnson-Greene to provide an update on our financial results for the quarter and full year ended December 31, 2025. Rita?

Thank you, Sankar. I'm thrilled to join the Ocugen team and support the company through its imminent transitions into a commercial enterprise. Starting with our fourth quarter results, research and development expenses for the 3 months ended December 31, 2025, were $10.7 million compared to $8.3 million for the 3 months ended December 31, 2024. General and administrative expenses for the 3 months ended December 31, 2025, were $6.1 million compared to $6.3 million for the 3 months ended December 31, 2024.

Ocugen reported a $0.06 net loss per common share for the 3 months ended December 31, 2025, compared to a $0.05 net loss per common share for the 3 months ended December 31, 2024. For the full year ended December 31, 2025, research and development expenses were $39.8 million compared to $32.1 million for the full year ended December 31, 2024. General and administrative expenses were $27.6 million compared to $26.7 million for the prior year. Ocugen reported a $0.23 net loss per common share for the year ended December 31, 2025, compared to a $0.20 net loss per common share for the year ended December 31, 2024.

Our current cash and cash equivalents extend our runway into the fourth quarter of 2026. This includes the recent raise of $22.5 million through an underwritten registered direct offering of common stock led by RTW Investments. In addition, if the $30 million in warrants from the prior Janus Henderson raise are exercised in full, it will extend cash runway into the second quarter of 2027.

That concludes my financial update. Shankar, back to you.

Thank you, Rita. We'll now open the call for questions. Operator?

And we will be taking our first question from Michael Okunewitch from Maxim Group.

Congrats on all the great progress you've made. I guess to start off, just given it is a 12-month primary endpoint for the liMeliGhT study, how confident are you in the ability to turn around the data from when you hit on that top line end point to actually releasing the top line data within first quarter of '27.

Huma?

Thank you for the question. We are very confident that we will be able to hit our time line.

All right. And then just for that endpoint, could you just remind us some of the modifications that you made for that particular navigation assessment course? And why you decided to go with a primary metric for RP?

Okay. So in terms of the mobility test that we are using proprietary to Ocugen that's [indiscernible] navigation assessment. It's the mobility test. That was approved as the primary endpoint for Luxturna that was called MLMT at that time. That was only designed for RPE65 mutations that covers only 1% to 2% of the RP landscape. This is a very sensitive and specific test as you can see that this is the broad RP indication trial, covering all clinicals and syndromic non-syndromic, all the genetic mutations that cause RP are included.

So this has uniform lux levels and intensity and lux levels from 0 to 9, and that has the ability to capture the change in real time, which is from the baseline up to 52 weeks. So this was also aligned with FDA. It's a validated test as well as this was approved by FDA and the only test that can capture the real change with functional outcome, improving the functional outcome or demonstrating the functional outcome in these mutations.

And just to let you know, we are the only trial globally that is covering all the majority of the gene agnostic metricians as we have covered this morning in one of our slides as well.

Certainly very helpful. And then last one before I jump back into the queue. For the Stargard program, it's looking like there could be an approval from another company for a chronic therapy by the time you file for 410ST. So I wanted to know how this might impact the opportunity or pricing potential? And if there's any reason that 410ST couldn't be complementary with other therapies as they come to market?

Yes, I'll take that. So there are other therapies out there. Obviously, what we have shown, if you look at the data we published an EYE, in 1 year, again, I wanted to restate all our trials were able to show treatment benefit in 1 year, unlike other trials out there, 2 years or more. And so the data we showed in 1 year is compelling. It looks superior. And also, our goal is to show also functional benefit. With the gene therapy, we are targeting the major pathways, which are complex in Stargard and GA with Aurora gene and also, we have ability to reset the homesites and bring make sure we create a healthy environment for retinal sensors rise. That's a very important factor.

We're not just trying to slow down the disease progression, we're working on the -- in our genes ability to control the inter network. So there is a big difference. And also, this is one and done. And if you have a one-and done on-one therapy, this will set up the standard of care PAUSE -- so we're not worried about other therapies if they come to the market. First, it's good. Those therapies will indicate the market and they'll create a market education and everything else. We will come back and then we may be behind them, but it's okay because what we believe we are going to send the standard of care for Stargard patients globally.

Huma?

Yes. I would like -- thank you, Shankar. So that I would like to add that this is the trial that we are also having the population 3 years of age and above versus the other trials that are very limited in the age population. Also, the inclusion exclusion criteria is very globally representing. Other than that, this is the OCU410ST is targeting early 2 advanced cases of Stargard disease. If you look at in the comparison, the safety and tolerability and efficacy that we have seen in terms of lesion growth reduction and also the functional structural outcomes has been trending in the right direction and promising from the clinical standpoint as well.

It's certainly an exciting time for the space. I'm looking forward to any further updates that you have.

Our next question comes from the line of Boris Peaker from Titan Partners.

Can you hear me? Sorry. Perfect. So for the RP 400, so the rolling BLA, when would we get the FDA feedback on your CMC part of the filing?

Typically, the CMC will be -- also we are planning to file this year. Obviously, I mean, the BA has right to -- request comments before or they will wait for entire section to be filed, even though they're internally reviewing, you may not expect anything before the actual final clinal module is filed.

Got it. And speaking of the FDA, have you discussed the ellipsoid zone as an endpoint with the agency. I'm just curious what their thoughts about it as maybe kind of a secondary endpoint? Is it something that could be incorporated into a label claim, -- would that make any kind of a difference from the commercial perspective? Just kind of general thoughts on that end point.

Yes. In ellipsoid zone, I mean, obviously, as we stated before, all our clinical trials, we're trying to show a benefit because diseases we are targeting significant unmet medical needs. So more delays and doing longer trial trials will take not only the resources model perspective, it's not doing benefit to the patients. If you're able to show a benefit using primary end points, what we picked which are acceptable. Obviously, the easy will be a secondary and some other analysis just to support further demonstrating -- this is showing a good functional outcome are related to functional outcome. That's important.

So if you do a longer trials like 2 or 3 years, sure, we can look into multiple options. So obviously, the agency's perspective, from FDA's perspective, they really focus on primary endpoint. If you hit the primary end point, you'll get the approval. If you had the secondary, yes, you can include it in the product insert and the label. And however, remember, all on clinical trials, we have obligation to continue them for 5 years for safety monitoring.

And so that means only data needed for filing after that second year, third or fourth tier and fifth year, we monitor the patient. Even we'll continue to monitor them with these secondary endpoints. At any point, the data is looking at. We can always add it to the label. So from FDA's perspective, you have to hit the primary end point to get the product approved. Secondary is not necessary. For approval. I mean if you hit it, it's good, they can put it in the label.

Got it. But I just want to understand also, have you spoken to docs like what's the commercial value. Let's say you could get on ellipsoid zone own label claim PAUSE obviously, not the primary endpoint, but still mentioned this positive in the label Would that really make a difference? Is this something that the docs actually care about? Or is it just kind of scientifically nice and curiosity more than anything else.

Yes, go ahead. Huma.

Boris, this is Huma. So in terms of your question, with MDA alignment, yes, all the protocols are approved with exploratory secondary endpoints. And yes, in terms of EZ, it's the new hot topic, well, for the clinicians in terms of functional outcomes and structural integrity for photoreceptor and retinal pigment epithelium. This is where actually FDA is leaning a lot based on these PAUSE particular conditions such as Stargard disease and geographic atrophy, secondary to age-related macular degeneration. In fact, there has been buying in consensus from the IRD physicians as well as the geographic atrophy AMD surgeons as well. And there is a real benefit to it, not only from the structural perspective, but also from functional. But yes, this is now being taken not only nationally in U.S. but also from Europe as well. And of course, there is a clinically meaningfulness in terms of functional outcome for easy. And that's what we are seeing. That could have a potential meaningful information when we are going to file our claim commercially.

And also geographic atrophy, Phase III in started that's why we're going to look at the entire Phase II data set this month, and then we are going to propose the endpoints with FDA and the EMA. So we do have an opportunity to introduce EZ as a secondary end point if the data is trending the way we anticipate.

Our next question comes from Swayampakula Ramakanth from H.C. Wainwright.

A couple of questions from me. Looking into the OCU410 program in the Phase II study, the medium dose short a 54% reduction versus the high dose, which showed a 36% reduction. So I'm just trying to understand when -- as you go into your Phase III study, what is going to impact your decision for dose selection? And also, do you think that PAUSE between these doses, you're actually seeing some sort of a plateau effect in the transgene expression.

Okay. Yes. I think the data we released, obviously, the high dose had less numbers in there. I would wait until we get the complete data set this month to make any influence. And obviously, agency's perspective, if lower dose issuing equal and a better effect, I mean, you would take that into Phase III, that's a standard practice. And so I suggest now we wait. Typically, what we look for in our genes and what we have seen in our RP studies to Typically, these genes require a threshold -- once again the threshold, we didn't see any dose response. So we're going to evaluate carefully once we get the full data set.

Okay. And then in the subpopulation where the baseline lesions were greater than equal to a greater than 7.5 millimeters square, you saw a 57% reduction in the lesion growth. So as you get into the Phase III study, would you have any restrictions in terms of the size of the lesions PAUSE -- or do you plan to use the same criteria as in Phase II, which was the all-comers?

That's a good question. Yes, this is why we do face to, right? PAUSE We're going to carefully evaluate and we go from what is the 2.5 to 22. And so we're going to evaluate and see because on the lower side, I mean, as you know, analytically, you'll have more variability. Of course, we're going to look at where the average patients fall, even though the large trials people have done, we have a lot of data. And we're going to look at all those metrics and see what is the right group to go into the Phase III.

All right. And then the last question for me is on the 10 program. where you're expecting to get the enrollment done this quarter and put up some interim data in Q3, in that data set, what are we really looking for, which can give us some indication of how the 27 BLA filing is going to go, especially I'm thinking about the signals on either on the structural side of things or on the functional side of things? And where -- what do you weigh more? And how should we be thinking when the data comes out?

So RK, thanks for your question. So in terms of the mass interim analysis that's coming later part of the year, PAUSE will be for 24 subjects, 16 treatment and 8 in the control, and this is the adaptive design that's a unique approach we have taken. And what are the what kind of data points we're going to present as we have presented this morning as well, of course, the primary endpoint, the lesion growth production as well as structural as well as functional, which is the visual equity and not -- last but not the least, of course, we are looking into the ellipsoid zone is the functional outcome, which is very unique, and that data was very well received from Stargard perspective that we have recently presented at one of the conferences as well. So yes, we are going to look all of that. And of course, safety and tolerability will be there as well as of right now it is trending in the right direction, and this is what we are looking into, to release mass interim analysis for those subjects later part of the year.

Our next question comes from the line of Elemer Piros from Lucid Capital Markets.

I'd like to ask a question about the primary measure visual function in the RP study. What would be a clinically meaningful improvement? Where do you draw the threshold toward that?

So thanks for your question. So basically, as we said that it's a change in loss level improvement from baseline. And as you know, there is a lot of mutations we are looking into. Technically, on lux level PAUSE and more because it's a validated protocol LG Dominum independent navigation assessment. That's what we are aiming for, and that's what our analysis is going to be based off of and as I've said earlier as well, there is a lot of heterogen IT with clinical diagnosis and roaming nonsyndromic forms. So of course, the clinically meaningfulness is greater than or equal to 1 lux level, depending on yes. Greater than equal to 1 lux.

And I think Elmer, as we Huma has stated, we validated these cores during Phase III with real patients and the course looks very robust. And based on our KOL input, they were extremely happy with this.

Yes. And what are some of the secondary end points that you will also look at to support that prime rate.

Of course, the secondary endpoints are, of course, on the visual equity loan lines, visual equity and also the patient-reported outcome scores we will be looking into it. And that is actually very well agreed and aligned upon with the FDA.

And one last question. Are both eyes are treated, if you could remind us.

Yes, it can meet the inclusion/exclusion criteria. Both the eyes are treated. It's a 2-to-1 randomization, a single subretinal injection and the control group will have a crossover after 1 year.

And the study is the worst time for analytic analysis set. So you would compare diverse to the control group.

Diversify in that group.

Yes. It's the study -- yes, PAUSE is compared to the control group. Yes.

Our next question comes from the line of Daniil Gataulin from Chardan.

This is Stephen on for Danil. For dry AMD, you mentioned the 50% responder rate. Were there any underlying characteristics that made a patient more likely to be a responder?

Are you talking about the 410 Yes. So in terms of that the responder rate, by the way, we have the inclusion criteria, which was very well uniform across the groups. And it was not in the baseline characteristics were that there was a mean age that we were looking into. And of course, the GA gets diagnosed at a certain age in the mid-70s was the main age. We were also looking at the lesion size, which actually PAUSE pretty much well worse with the Oaks and Derby trials and Apple has got approval on it was 7.5 millimeters square, that was the mean as well, up to 8.03%.

And in terms of the baseline characteristics, the responders basically responded on the medium dose as well as on the high dose as well. So there was not really any other unique criteria that we would say at this point till we get our final clinical study report at that point. But at this point, it seems like it was uniform across those groups.

This concludes the Q&A portion. I will now turn the call back over to Chairman, CEO and Co-Founder, Dr. Shankar Musunuri.

Thank you, operator. 2025 was marked by important clinical progress strategic business development and essential financing accomplishments across the organization. We are entering 2026 with a strong momentum and a clear line of sight to multiple catalysts that will further advance Ocugen's position as a biotechnology leader in gene therapy for blindness diseases. We expect to deliver full Phase II data for OCU410 this month, complete enrollment for OCU410ST, initiate Phase III for OCU410 in geograph atrophy and begin our rolling BLA submission for OCU400. I want to thank our employees, investigators, patients and shareholders for their continued support. We look forward to updating you on our progress. Have a great day.

Thank you all for joining. You may now disconnect.

Good morning, and welcome to Ocugen's webcast to discuss data from the first half of patients completing 1 year since treatment in the OCU410 Phase II ArMaDa clinical trial for geographic atrophy. Please note that this call is being recorded at this time. [Operator Instructions]

Joining on today's webcast are Dr. Shankar Musunuri, Chairman, CEO and Co-Founder; Dr. Huma Qamar, Chief Medical Officer; and Dr. Arun Upadhyay, Chief Scientific Officer, along with distinguished clinical trial investigators. Dr. Jay Chhablani, Dr. Arshad Khanani and Dr. Lejla Vajzovic as this webcast is being recorded. A replay with the accompanying slide presentation will be available on the website. Thank you.

Thank you, operator. Good morning, and thank you for joining this important update on our OCU410 program. Today's presentation will focus on clinical updates from the Phase II ArMaDa trial, along with some new data from Phase I. This presentation contains forward-looking statements regarding OCU410's clinical development, regulatory time line and therapeutic potential for geographic atrophy. These forward-looking statements are subject to significant risks and uncertainties.

We have assembled an exceptional group of clinical and scientific leaders to walk you through every aspect of our program. Dr. Arun Upadhyay, our Chief Scientific Officer, will dive deep into OCU410's novel mechanism of action, how RORA modulation addresses multiple pathways implicated in GA progression. Dr. Huma Qamar, Chief Medical Officer, will outline our comprehensive clinical development plan, including the rationale for our regulatory strategy.

Dr. Jay Chhablani from the University of Pittsburgh and UPMC Vision Institute and President of NetraMind will present Phase I ArMaDa trial data updates. Dr. Lejla Vajzovic, Duke University will discuss the Phase II interim results, highlighting efficacy and safety findings.

Finally, Dr. Arshad Khanani from the University of Nevada and Associates will join his colleagues for the Q&A. I'd like to set the clinical context for today's discussion by reviewing the unmet medical need in geographic atrophy. Geographic atrophy or GA, is an advanced form of dry age-related macular degeneration. GA is characterized with progressive irreversible degeneration of the retina and retinal pigment epithelial cells in the macula, the central portion of the retina critical for detailed vision. This process leads to irreversible loss of central vision with patients experiencing progressive scotomas that coalesce and expand over time.

Currently, 2 million to 3 million patients in the combined U.S. and European markets suffer from GA. This represents an enormous population of visually disabled individuals with limited therapeutic options in the U.S. and no therapeutic options outside of the U.S. Until very recently, there were no approved treatments for GA. Just in the last few years, 2 therapies have been approved, SYFOVRE and IZERVAY. Combined, these represent over $1 billion in combined U.S. annual sales, underscoring the significant unmet medical need and market opportunity. However, these approved therapies have significant limitations. Most critically, they each address only 1 of the 4 major pathways implicated in GA disease progression.

Additionally, both require frequent intravitreal injections, 6 to 12 times per year. These injections carry cumulative risks, including endophthalmitis, retinal detachment, inflammation and other serious complications. Patients must commit to lifelong monthly or bimonthly office visits for injection administration. This is where OCU410 represents a paradigm shift. OCU410 is designed to address all 4 pathways associated with GA through a single subretinal injection of an AAV5 delivered RORA gene therapy. As a onetime administration that potentially provides durable benefit, OCU410 offers GA patients an unprecedented opportunity for comprehensive disease modification without the burden of chronic injections.

We are executing well on our ambitious development pathway for OCU410. You will hear more about data from approximately 50% of patients in the Phase II clinical trial at 1 year today. We'll provide a full data set later this quarter. We also plan to initiate our Phase III pivotal trial later this year. In 2027, we target completion of Phase III enrollment, allowing us to begin our follow-up and final analysis, OCU410 Phase II clinical trial. In 2028, we anticipate generating top line Phase III data and submitting our biological application, or BLA to the FDA.

Now I will hand it over to Arun. Arun?

Thank you, Shankar. And I will now walk you through the scientific rationale for OCU410 design and its multi-pathway mechanism of action. OCU410 utilizes a modified therapeutic approach targeting RORA, the retinoid-related orphan receptor alpha. RORA is a nuclear receptor that functions as a master regulator of multiple homeostatic pathway in retinal cells, particularly in the retinal pigment epithelium and photoreceptors.

Our preclinical research has demonstrated that OCU410 provides 4 distinct therapeutic benefit. First, anti-drusen activity. In the model of macular degeneration, we have shown that RORA activation leads to reduced drusen burden and improved overall retinal architecture. This is significant because drusen accumulation is a hallmark of AMD progression and is thought to contribute to RPE dysfunction and photoreceptor death. By reducing drusen and supporting RPE health, OCU410 addresses a fundamental aspect of GA pathogenesis.

Second, antioxidative protection. Oxidative stress is a major driver of both RPE and photoreceptor cell death in GA. In cell survival assay using ARPE19 cells, which is like representative of human ARPE cells, RORA overexpression provides robust dose-dependent neuroprotection against oxidative stress. This indicates that OCU410 can enhance the intrinsic antioxidant defense of retinal cells.

Third, anti-inflammatory modulation. GA progression involves microglial activation and local retinal inflammation that exacerbates photoreceptor loss. In microglial cell model, RORA expression suppresses pro-inflammatory cytokines and chemokines, effectively inhibiting this harmful inflammatory cascade. By reducing neuro-inflammation, OCU410 protects photoreceptors from immune-mediated injury.

And fourth, anticomplement activity. Complement system activation has recently emerged as a critical mechanism in GA pathogenesis. RORA upregulates CD59, an important complement regulatory protein that protects photoreceptors and RPE from membrane attack complex formation. This prevents complement-mediated cell death another key pathway in GA progression. What makes OCU410 particularly innovative is that it targets these 4 convergent pathways with a single therapeutic intervention. Rather than blocking one mechanism as the existing approved therapies do, OCU410 simultaneously addresses multiple critical disease mechanism. This multi-pathway approach has the potential to provide more robust and potentially more durable therapeutic benefit. Now to Huma.

Thank you, Arun. The Phase I ArMaDa trial was conducted as an open-label dose escalation dose-ranging study designed primarily to assess the safety and tolerability of OCU410 in patients with geographic atrophy secondary to dry age-related macular degeneration. The trial enrolled a carefully selected patient population with documented GA, and we implemented a rigorous dose escalation protocol with formal safety monitoring at each stage. The dose escalation schema utilized a 1:1:1 randomization and included 3 cohorts. The low-dose group received 2.5 x 10 to the power of 9 vg per ml in 200 microliter.

The medium dose group received 5 x 10 to the power of 10 vg per ml in 200 microliter and the high dose group received 1.5 x 10 to power 11 vg per ml in 200 microliter. Each cohort consisted of 3 patients. Importantly, after treating each dose cohort, we convened our Data and Safety Monitoring Board for formal safety review at 4 weeks post injection before proceeding with dose escalation. This rigorous DSMB monitored approach ensured that we identified any safety signals early.

For primary endpoints, we assess safety and tolerability through adverse event monitoring, serious adverse event tracking and intraocular pressure measurements. Secondary endpoints included structural assessment via indirect ophthalmoscopy and fundus autofluorescence imaging to detect any retinal changes. We also included several exploratory endpoints designed to generate preliminary efficacy signals. These included quantification of drusen volume using spectral domain OCT, careful monitoring for conversion to wet AMD, microperimetry testing using the MAIA device to assess retinal sensitivity, patient-reported visual function using the NEI visual function questionnaire 25 and comprehensive immunological monitoring, including humoral and cellular immune responses as well as viral vector shedding analysis.

We did not exclude patients with CNV, choroidal neovascularization in the fellow eye. This allowed us to treat a broader patient population while maintaining rigorous monitoring for treatment-related exhibition of wet AMD. I will now turn the call over to Dr. Jay Chhablani, one of our clinical trial investigators, who will review the safety and efficacy updates from Phase I portion of the study.

Thank you, Huma. OCU410 Phase I enrolled 9 elderly AMD patients with asymmetric disease. Study eye 47 letters BCVA versus fellow eye 60 letters with a baseline lesion size ranging between 7.7 to 8.2 millimeters square, choosing the eye with worse visual acuity to receive treatment. No cases of ischemic optic neuropathy, vasculitis, endophthalmitis or choroidal neovascularization were observed, representing a safe -- relatively safe and tolerable profile for OCU410 among the doses tested. This favorable safety and absence of serious inflammatory or ischemic complications support advancement to Phase II with dose escalation and expansion studies to study efficacy.

OCU410 treatment demonstrated a 20.2% reduction in geographic atrophy lesion growth at 12 months compared to untreated fellow eyes. This intra-patient comparison leverages the asymmetric disease model as an internal control, excluding 3 subjects, 2 with foveal detachments during surgery, 1 high-dose patient with loss to follow-up, and this helped us to determine the treatment effect.

The 20.2% relative reduction in lesion progression rate represents a meaningful early efficacy signal suggesting OCU410 slows GA progression. The most striking finding from Phase I trial is the preservation of photoreceptor structure in treated eyes as measured by spectral domain OCT. At 12 months of follow-up, we observed OCU410 treated eyes demonstrated 60% slower loss of the ellipsoid zone, which is a structural exploratory endpoint for the study, ellipsoid zone compared to untreated fellow eyes.

The EZ that is ellipsoid zone represents the inner segment, outer segment junction of photoreceptors as visualized on spectral domain OCT imaging. This is a critical anatomical marker of photoreceptor health and integrity and loss of ellipsoid zone indicates photoreceptor degeneration and death. Preservation of the ellipsoid zone indicates maintained photoreceptors structures and by extension, likely maintained or improved photoreceptor function.

The 60% reduction in EZ loss rate indicates that OCU410 treatment is substantially slowing the rate of photoreceptor degeneration compared to the natural history observed in the untreated fellow eye of the same patient. This is consistent with our preclinical findings regarding RORA's neuroprotective and antioxidative mechanisms, and it provides the first clinical evidence that OCU410 can preserve photoreceptor structure in GA patients. Building on our ellipsoid zone findings, we extended our analysis to examine the broader EZ-RPE complex, a composite measure that includes both the photoreceptor layer and the underlying RPE.

The EZ-RP complex represents the functional unit of photoreceptor RP interaction. Loss of this complex indicates degeneration of both photoreceptors and the supporting RP layer. Preservation of EZ-RPE complex, therefore, suggests that OCU410 is protecting both retinal layers simultaneously. Our analysis demonstrated OCU-410 treatment resulted in reduced loss of EZ-RPE complex at 12 months post treatment compared to untreated fellow eyes, indicating a treatment effect on both the photoreceptor and RP compartments. This finding is particularly significant because it suggests that RORA modulation is working at multiple levels within the retina.

We see photoreceptor protection consistent with our antioxidative mechanism. The ability to protect both photoreceptors and the RPE with a single therapeutic intervention underscores the advantage of multi-pathway targeting approaches. We are now not just addressing one aspect of GA pathogenesis, we are supporting the health and survival of the entire photoreceptor RP unit. These structural findings provided compelling rationale for advancing to Phase II with controlled efficacy endpoints in a larger patient population.

Now back over to Dr. Huma Qamar.

Having established the safety profile and observed promising structural preservation signals in Phase I, we advanced to Phase II to assess OCU410's efficacy in slowing GA progression. The Phase II trial employed a randomized control design with 1:1:1 randomization enrolling a total of 51 patients across 3 groups, high dose, medium dose and an actual control. The control group, medium dose and high-dose treatment group all included 17 patients. The control group received no treatment. The medium dose included 17 patients who received 5 x 10 to power 10 vg per ml in 200 microliter and the high-dose treatment group included 17 patients who received 1.5 x 10 to power 11 vg per ml in 200 microliter.

Safety monitoring remained rigorous with data and safety monitoring board reviews conducted at 4 weeks post injection for both initial and subsequent cohorts. Our primary efficacy endpoint was change in GA lesion size quantified in square millimeters using fundus autofluorescence imaging. The change in lesion size from baseline to 12 months represents a direct measure of disease progression or stabilization.

The rationale for lesion size as the primary endpoint is well established in ophthalmology. GA lesion size measured by FAF correlates strongly with functional decline in visual disability. This endpoint has been adopted by regulatory agencies for GA trials. Secondary efficacy endpoints included change in low luminance visual acuity, a functional measure of vision from baseline at 12 months.

I will now pass the call to Dr. Lejla Vajzovic.

Thank you, Huma. OCU410 Phase II enrolled 51 elderly age-related macular degeneration patients with mean age 75.9 years with the treated eyes averaging 55.1 letters in best proactive visual acuity, 30.32 EDTRS letters in luminance visual acuity and lesion size of 8.03 millimeter square with patients from early to late-stage geographic atrophy suitable for tracking disease progression enrolled.

OCU410 demonstrated a clean safety profile with no choroidal neovascularization, retinal vasculitis, intraocular inflammation or serious severe adverse events, differentiating the program from monthly and every other month injections competitors that may experience CMV vasculitis, intraocular inflammation, serious and severe events.

As a single administration of gene therapy, OCU410 eliminates the ongoing cumulative injection-related risks that patients on approved therapies experience every month or other month basis. The potential therapeutic effect of OCU410 is expected to be durable and lifetime, a one-and-done treatment. This represents a paradigm shift in geographic atrophy management from chronic injection-dependent therapy to durable disease modification.

At 12 months, OCU410 treatment resulted in 46% statistically significant reduction in GA lesion growth in treated eyes compared to control eyes and the p-value of 0.015. The analysis included 23 eyes, 5 control eyes, 18 eyes in treatment group, of which 10 treated eyes received medium dose and 8 eyes received high dose. For this analysis, the medium and high-dose treated groups were combined, as you can see. This population included both patients with foveal involving and subfoveal atrophy patients.

The p-value of 0.015 provides a robust statistical support for the treatment effect, indicating the observed benefit is significant. Currently, a 46% reduction in lesion growth rate means OCU410 treated patients are experiencing slower expansion of the atrophic lesions. This translates to delayed central vision loss and maintenance of youthful vision for longer period.

With the Phase II treated population, we examined lesion size reduction separately for the medium and high-dose groups as the data on left shows. The medium dose group demonstrated a 54% reduction in lesion growth compared to control. The high-dose group demonstrated 36% reduction in lesion growth compared to control. This data reveals an important dose response relationship, but not the relationship one might initially expect. The medium dose appears to be providing better efficacy compared to high dose. This finding warrants careful interpretation.

Several factors could explain why high dose appears less efficacious. First, there may have been baseline imbalances between the medium and high-dose groups. For example, high-dose group may have had slightly larger or more aggressive lesions at baseline. Second, the high-dose group has a fewer evaluated patients, limiting statistical power. And third, and perhaps most intriguing, there could be biological factors related to excessive transgene expression, what we call a plateau effect where the additional vector doesn't provide additional benefit.

Both dose groups showed statistically significant improvement versus control with medium dose with a p-value of 0.02 and high dose, the p-value of 0.05, but numerically superior, the medium dose is clear. We are looking forward to presenting the complete finding for all subjects enrolled post the beta lock analysis. The right panel shows a subgroup analysis of patients with baseline GA size equal or greater than 7.5 millimeter squares. These are patients with more advanced atrophy.

In this subgroup, OCU410 demonstrates a 57% reduction in lesion growth and a 14 compared to controlled eyes. This 57% reduction in lesion size suggests that OCU410 may be more effective in patients with substantial disease burden, exactly the population we want to treat. In addition, both medium and high-dose OCU410 were equally effective in decreasing the lesion size in patients with large lesion size.

I want to now compare OCU410's efficacy in a broader clinical context by comparing our results to currently approved therapies. OCU410 at 12 months demonstrate 46% reduction in lesion growth compared to control. This represents our interim primary efficacy analysis in this Phase II. For comparison, published data on approved therapies, specifically SYFOVRE and IZERVAY, specifically looking at OAKS and DERBY trials, the published data by Heier et al. in 2023 shows approximately 22% reduction in lesion growth at 24 months.

I would like to emphasize that there has been no head-to-head trials that have been comparing -- that have compared or conducted between OCU410 and approved therapies. The direct comparison is clearly limited, but we're comparing the Phase II assessor blinded control study to published trials with different patient population trial designs, follow-up periods as well. And that said, there seems to be a clear contrasting in difference.

OCU410's 46% reduction at 12 months compared to 22% approved therapies at 24 months suggests a potentially greater and even twofold therapeutic advantage through this interpretation should be very much taken cautiously with acknowledgment of different trial contexts.

We also examined response rates, the proportion of patients achieving clinically meaningful benefit. OCU410 demonstrates significant response rates with up to 50% of treated patients achieving greater than 50% lesion size reduction compared to control at 12 months. This response rate analysis provides perhaps the most compelling evidence of OCU410's clinical value.

A therapy that provides substantial benefit of half of treated patients represents a transformative advance for populations facing otherwise relentless disease progression. I will now turn the call over to Dr. Huma Qamar to summarize the clinical updates.

Thank you, Lejla. In conclusion, the evidence presented above supports OCU410 as a transformative therapy for geographic atrophy. First, OCU410 employs a comprehensive multi-pathway mechanism of action. Unlike approved therapies that target a single pathway, OCU410 modulates RORA to activate multiple protective pathways simultaneously. The unique 4-way mechanism of action have been rigorously validated in preclinical models and supported by clinical efficacy data.

Second, OCU410 demonstrates compelling clinical efficacy data, 46% reduction in lesion growth at 12 months compared to control, 57% reduction in lesion growth at 12 months compared to control in patients with larger lesion size greater than or equal to 7.5 millimeter square at baseline. Up to 50% of patients achieved greater than 50% lesion size reduction compared to control.

And third, OCU410 has established a very favorable safety and tolerability profile. No serious adverse events related to OCU410 have been reported to date. Fourth, OCU410 addresses a massive unmet medical need with significant market potential and estimated 2 million to 3 million GA patients in the U.S. and EU with limited treatment options and potential onetime definitive treatment versus a lifetime of monthly or bimonthly injections for approved therapies and multi-pathway targeting mechanism offering potential for more durable and comprehensive disease modification.

Before I open up the Q&A, I would like to ask Dr. Arshad Khanani a question based on what we have all seen today. What are your thoughts on the OCU410 data? And how do you see it fitting into your clinical practice?

Thank you, Huma. Good morning everybody. Congratulations to you, Shankar and the Ocugen team for this data set. I've been involved with numerous programs for the development of treatment of geographic atrophy, and we are lucky to have, obviously, the 2 approved treatments. But as highlighted, there are several things that are important to consider here, and this program addresses unmet needs. When I'm looking at the data from Phase I, Phase II, obviously, this is a onetime gene therapy. The biggest burden we have patients in clinic is the treatment burden of injections every month and every other month. And as we start those treatments, over time, there's a very high dropout for patients. And of course, each injection brings a risk of endophthalmitis and other things, including CNV.

So we are lucky to have treatments, but the next generation of treatments for geographic atrophy, we have to address several unmet needs. And I think when I look at this program, I'm looking at, number one, safety. When it's a onetime gene therapy, we need to make sure it's safe. We have not seen any safety signals here. And as you know, subretinal gene therapy obviously does not cause immune responses. And I'm happy to see that we have not seen any intraocular inflammation, any endophthalmitis or any vasculitis.

Number two is efficacy signal. You have a consistent efficacy signal that you can see in Phase I and of course, the interim analysis from the Phase II. So that is very important. And of course, very excited about the ellipsoid zone data that was presented by Dr. Chhablani. I think that is an important endpoint that is now utilized by many programs as a primary endpoint.

So overall, when I look at this data set, I'm seeing the things I would like to see in Phase I and Phase II is no safety signals, efficacy that is consistent. So I'm excited to see the full data set from Phase II and very excited to see the program will move forward and I'll be enrolling patients, obviously, in the Phase III program. And in terms of the unmet needs, I think a onetime gene therapy for GA will be widely adopted because these are patients that have very difficulty coming in every month and every other month. And then, of course, many of these patients have bilateral disease.

Great. Thank you so much, Dr. Khanani. And now operator, please open up the call for questions.

[Operator Instructions]

Our first question comes from the line of Robert LeBoyer with NOBLE Capital Markets.

Congratulations on all the data and thank all of you for those comprehensive discussions and explanations about the mechanism and the data. One of my questions has to do with the EZ zone. And I was hoping you could give a quick review of the biology there, the effects you've seen and the significance and perhaps if any of the approved drugs have that similar type of effect.

Dr. Jay Chhablani, the question is for you.

Thanks, Huma. This is Jay Chhablani. I am a retina specialist. I have been involved in the analysis of this particular structure, and I have a keen interest in a retinal structure. So ellipsoid zone actually represents the key anatomical biomarker of the photoreceptor cells. And photoreceptor cells are the one which pretty much does the most of the job to save the vision.

So luckily, with our high-resolution imaging now, we are able to see this structure and OCT gives us almost a histological view of the retina. And so it looks -- so this structure has been evaluated in many diseases, primarily on macular degeneration because the available treatment options have been focused on saving the vision or delaying the progression, but this structure has not been evaluated in any of the trials earlier. Though some post-hoc analysis has been done, but I really admire Ocugen team that they are looking at this structure very early in the clinical trial, and we are seeing really fantastic results in Phase I, and we are looking forward to the Phase II as well as Phase III in this analysis.

So overall, I would say that this is a structure which has been used for approval for the recent implant for macular telangiectasia, which is a different disease than macular degeneration. So it looks like the FDA is very much open for accepting this as an anatomical outcome measure, which will certainly change the way we are looking at the clinical trials and definitely help us to improve our outcomes.

One more thing I'll add is that the recent studies which we are doing, they are also showing that this structure is related or correlated with functional vision as well. So which again is something which FDA wants as a functional vision outcome as well. So I think that this will become a very important clinical biomarker.

Okay. That's very helpful. And I also had a question. I agree, this is very interesting data, and I'm also looking forward to more of it. Could someone lay out some of the milestones or expected time frames for additional data?

Yes, I can answer that. So we are anticipating our full data set towards the end of the quarter, and we are also looking at the Phase II full study report at that time. So we will be sharing the information accordingly as we also anticipate Phase III initiation in 2026 as well. And the Phase II data will also be pivotal in terms of defining our strategy for Phase III in 2026.

Our next question comes from the line of Elemer Piros with Lucid Capital Markets.

Congratulations. What I'd like to ask is if you have any idea of which dose would you take forward into a pivotal trial? That's my first question. And perhaps to Dr. Khanani or some of the other experts, in a pivotal trial, would you recommend to restrict the population to certain lesion size or stage of the disease? Or would you recommend to examine the entire population without restrictions?

Yes. So in terms of your first question in terms of the dose, we are currently evaluating both the doses, medium dose and high dose as the study is not closed yet. Once the data set is available for Phase II and we close the study, that will be the point that we will be carefully analyzing the data and coming up with the efficacious dose for Phase III. And for the other question, I would let either Dr. Khanani or Dr. Lejla Vajzovic to answer that question.

Thank you, Huma. I can take that, and then I'm sure Lejla will follow up. So those are great questions. I think when you're designing the Phase III program, you use the full data set from Phase II to kind of evaluate the efficacy signal and then you tease out the population that will have the highest benefit. So here, obviously, we are looking at an all-comer patient population. But I think I'm looking forward to the full data set. And then after that, we'll be able to evaluate which patient population will be the right one.

But in general, yes, we do limit the size of the GA lesion, very similar to the GATHER2 program or DERBY and OAKS program on average, 7 to 8 millimeter square. But of course, you have patients with smaller lesion and larger lesion. As you know, some programs have all-comer patient population like we have here where you have foveal and non-center point involving patients, while others like GATHER2, we only had non-center point involved patients.

So I think those are really, really good questions, and I think we'll be able to refine those criteria after we have the full data set. But the way we are looking at this data set, this analysis clearly -- these interim results clearly show that there is a benefit that appears to be on average in most patients, which is actually very good news. But I think once we have the full data set, we'll be tease that out for you. Lejla, anything from you?

Yes. Thank you. Thank you, Arshad. You said really beautifully, just to add and to point out, I think it's exciting to see such a positive results this early with such a, in general, progressive relentless disease. I similarly look forward to seeing the complete data set to help us really educate ourselves how to move forward with the Phase III in terms of what dose and also baseline characteristics for the patients role. But in this diverse patient population with foveal and extrafoveal lesions included, I think it's exciting to see results in both doses.

And perhaps just a little follow-up. Since OCU410 addresses the complement pathway, would there be a necessity to follow up with currently existing treatments down in the future once approved?

So I will direct this question to either of our KOLs. Arshad, do you want to take that?

Can you rephrase that? Are you asking about that the comparator will have to be an approved treatment? Is that the question?

No. Just -- I mean, in the future, once 410 is approved, is there a rationale to further treat once the gene therapy is applied with complement inhibitors, currently approved drugs since OCU410 already addresses the complement pathway?

Yes, that's a very good question. I mean I think the efficacy we are seeing with this program is in line or superior based on Phase I or Phase II interim data compared to what we have currently. So I think the goal here is that this will be a onetime gene therapy that will obviously deliver a similar efficacy or better efficacy without the burden of injection. So I don't think at this stage, I would think that we will need to add complement inhibitors on top after giving this to patients. But obviously, in real world, many different things happen. But I think the hope here is that we'll be able to decrease the treatment burden for our patients significantly with this onetime gene therapy modulating complement pathway and, of course, other pathways as you saw earlier.

Next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

Thanks, Ocugen team for doing this for us this morning. A couple of quick questions. So for the physicians online, you were stating that with the current therapies, it could potentially become burdensome that adoption with the potential -- with the current therapies could wean off over time. So when 410 comes to the market, would you consider this as the first therapy for a patient who comes in with this indication? Or would you wait to see how patients react to the currently approved therapies before giving the gene therapy? I'm just trying to figure out, is there going to be a sequencing thing or you really don't need sequencing based on the safety and efficacy that you're seeing with 410?

Lejla or Arshad, do you want to take that?

Yes, I think we can both. Happy to take it on. And currently, with geographic atrophy, patients often come in with, unfortunately, visual acuity affected, at least to a retina specialist office. So I think time is critical to kind of help them preserve the vision and continue to stay active in their day-to-day activities. And for that reason, I most certainly would want to offer more durable and onetime approach.

Now the current therapies that are approved, we use on a monthly or bimonthly basis. And while we know there's efficacious in clinical trial settings, we don't have the best way of following or assessing how this particular patient is responding to therapy. So we are treating the patients knowing our results from clinical trials show up to 22% of reduction over time but the current real world doesn't have the best way to follow these patients and response. And there's much work being done to change this.

Lots of software analysis from various companies are underway and most likely will be available in the future, but not currently. And then to kind of summarize my answer, I would love to kind of just start with the approach that solves us, so to speak, for the patient and it provides durable option once the disease is diagnosed, and we most certainly see visual acuity affected.

Yes. I would like to add to what Lejla was saying is that I'm a treater, I use complement inhibitors in my practice, and I'm implementing them earlier and earlier to preserve central function and then to slow down the growth of the lesions. But what is the hope that I give to my patients that come in? I say this is the first generation of treatments. We are lucky to have them, but we have other treatments coming down the pipeline. And in the future, just like what happened with wet AMD, we went from PDT to anti-VEGF and then we went from monthly anti-VEGF to bimonthly and then every 3 to 4 months, and then now we're looking at possible 6 months with TKI.

So what I'm telling my patients is that we have more durable treatments coming in. Let's hold as much retinal tissue saved as I can now. So I think the biggest population right away once 410 is approved would be the patients who are already treated with complement inhibitors. And if we show efficacy, as I said, similar or close enough or even better, which I would be very happy with, then those patients that are already established will be very interested in getting gene therapy because they'll be on injections for a while.

Now obviously, not every patient can get gene therapy because we have to go to the operating room, but I think majority of the patients can. So I think the established market definitely will be right there for us to help so that we can reduce the treatment burden. So just to add to what Lejla said, everything else in terms of gauging the benefit, and I totally agree with Lejla.

Huma, I just have a second 2-part question. This is on the responder rates. So you had seen a 57% reduction in baseline lesions. Does OCU410 modify mechanism, does it require a certain existing level of disease activity to show a maximum effect? And also on the 50% responder rate, did you get to characterize the nonresponders in terms of either genetic markers or baseline inflammatory profiles or any such thing that could help us understand why we are not seeing as much response as the ones that responded?

No, the answer is no and no to both. And there is the inclusion. If you look at the inclusion/exclusion criteria of our protocol, it has been very consistent with 2.5 to 21.5 millimeter squares up to 8 disc carriers and it's pretty much consistent with all the products that have been approved and also geographic atrophy is the last stage of the dry age-related macular degeneration. We also had foveal and parafoveal lesions, too. But in terms of the markers and the response rates at this point, we are only mentioning different reduction across different combined dose groups as well, which is great.

Also, if you look at that, there was a greater reduction observed in subjects with greater than or equal to 7.5 millimeter square at baseline as well. This is all preliminary interim analysis that we are looking into. We will have more information as what we -- with actual control that we have. But to your question, it's no and no to both. Arun, do you want to add something to it?

No.

[Operator Instructions]

We have a question from Michael Okunewitch with Maxim Group.

Congratulations on the progress. I would just like to see if you could comment a little bit on the importance of some of the different measures you used, in particular, ellipsoid zone loss versus lesion growth and how these might definitely translate into a patient's visual outcomes.

Yes. So I would direct this question to Dr. Jay Chhablani.

Thanks, Huma. So I would say that ellipsoid zone is a very critical structural biomarker, which now we are able to see on OCT scans. And this biomarker has been shown to be related to the functional vision as well. So we have been looking at this biomarker for now for quite some time. And I think that this is one of the first trials who -- which is looking at this biomarker at a very early stage of the clinical trial.

So ellipsoid zone becomes very critical in regards to the retinal sensitivity, which has been shown to be related with -- which has been shown on micro perimetry as well as related to the contrast sensitivity. So I think that this will certainly become a very important anatomical biomarker on OCT.

The other trials or, I would say, the other GA trials or other drugs which have been approved, they have used fundus autofluorescence, which is definitely one of the very important imaging which we use in our clinic but considering that fundus autofluorescence does not give us a depth result information, which we get from OCT. So therefore, we prefer to look at the ellipsoid zone over fundus autofluorescence imaging.

Arshad, do you want to add anything to it?

Yes, definitely. I think it's a great question. And I would say that ellipsoid zone is becoming an important biomarker, as Jay was saying. And we actually had ellipsoid zone Delphi panel and I presented the data at AO, where we actually have a steering committee, which I'm part of, and we have world-renowned experts who are part of the panel. And I think it's consistent that ellipsoid zone is going to be the primary endpoint in many trials.

I think one paper I want to direct you to is the ReCLAIM 2 paper. Of course, Justis Ehlers at Cleveland Clinic, who was a good friend has led the work for ellipsoid zone. He was also the one that actually helped Stealth get ellipsoid zone as the primary endpoint for their Phase III trials.

When you look at the ReCLAIM-2 data, there was a reduction in ellipsoid zone attenuation or loss, and it was also associated with 10 let or greater gain in LLBCV, low luminance BCV versus placebo. So I recommend if you want to read more about it, please read that paper. But the bottom line is that ellipsoid zone will be something that most companies will be using as a primary endpoint in the future because, as Dr. Chhablani said, is more associated with the functional benefit.

If I may just add, like it was very well described by my colleagues. We're also seeing this important structure, not just be of great value in geographic atrophy, but other macular diseases. So one of the approved therapies now for rare condition for MacTel 2 and ENCELTO was approved based on exactly this, the anatomic measurement of EZ changes over time.

So clearly, there's a landscape shift in our specialty from looking [indiscernible] primary endpoint for trials, but really looking at anatomic features of the OCT to help us really see the changes, which do translate to changes in function for the patient as well.

And then I just would like to -- if you could help me understand the decision to select 50% lesion size reduction versus control as a threshold for the responder analysis. Is that the meaningful threshold? Or could something less like 20% still be significantly meaningful for these patients?

No, this is Arun Upadhyay. So if you look at approved therapy and with just like around 20% reduction in lesion growth has been the basis for approval. So we just wanted to look at our interim data setting various cutoff and see how this patient population responding. So it is not that we need to have a 50% to demonstrate significant. But what we are highlighting that with this therapy, even close to 50% patients -- subjects are responding more than 50% reduction lesion growth, which is really remarkable and compelling at this stage.

So we can think of this as a very high [indiscernible].

And I think from a clinical perspective, if I may add, we are talking about differences between monthly or bimonthly injections for our patients, elderly patients versus potentially doing a one-and-done approach. I think that has to be taken into context as well because the burden treatment of getting monthly or bimonthly injections, especially at that age group is quite troubling and most patients can't keep up with such a frequent injection volume.

Yes, I agree. And I think the key is as a clinician, if you have an approved gene therapy, even if it's less efficacious than approved treatments, let's say, it's 18 or 15, obviously, we are seeing better here, but I think it brings value. A onetime procedure, as highlighted by Lejla is something we have to keep in mind that, that will bring so much value to the patients, even if the efficacy is slightly less than approved treatment, I think it still will be adopted because of the treatment burden issue that we face with our patients.

And also, we have many patients with wet AMD that are needing treatment that also have geographic atrophy. And if you look at real-world studies, overall GA patient population, 30% to 40% of patients that are being treated for wet AMD also are getting [indiscernible] 40% -- 30% to 40% of patients who are treated with anticomplement have concurrent wet AMD. So having a onetime treatment to relieve burden for these patients that have even more burden will be very important and very well accepted by the patients as well as the physicians.

This concludes the Q&A portion. I will now turn the call back over to Chairman, CEO and Co-Founder, Dr. Shankar Musunuri.

Thank you. Looking forward, our regulatory path is clear. We anticipate Phase III initiation in 2026 using the safe and efficacious dose as established from Phase II ArMaDa trial post database lock. With successful Phase II outcomes, OCU410 has the potential to become a paradigm-shifting therapy for geographic atrophy, offering GA patients a durable, well-tolerated onetime gene therapy that comprehensively addresses the multiple pathways driving disease progression. Thank you for joining us, and have a great day.

Ladies and gentlemen, that concludes today's call. Thank you all for joining, and you may now disconnect.

Good morning, and welcome to Ocugen's Third Quarter 2025 Financial Results and Business Update. Please note that this call is being recorded at this time. [Operator Instructions]

I will now turn the call over to Tiffany Hamilton, Ocugen's Head of Corporate Communications. You may begin.

Thank you, operator. And good morning, everyone.

Joining me on today's call and webcast is Dr. Shankar Musunuri, Ocugen's Chairman, CEO and Co-Founder, who will provide a business update and an overview of our clinical and operational progress. Ramesh Ramachandran, our Chief Accounting Officer, is also on the call to provide a financial update for the quarter ended September 30, 2025. Dr. Huma Qamar, Chief Medical Officer, will be available to answer questions following the presentation.

This morning, we issued a press release detailing associated business and operational highlights for the third quarter of 2025. We encourage listeners to review the press release, which is available on our website at ocugen.com. This call is being recorded and a replay with the accompanying slide presentation will be available on the Investors section of the Ocugen website for approximately 45 days.

This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are subject to risks and uncertainties. We may, in some cases, use terms such as predicts, believes, potential, proposed, continue, estimates, anticipates, expects, plans, intends, may, could, might, will, should or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements include, but are not limited to, statements regarding our clinical development activities and related anticipated timelines. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission, the SEC, including the risk factors described in the section entitled Risk Factors in the quarterly and annual reports that we file with the SEC. Any forward-looking statements that we make in this presentation speaks only as of the date of this presentation. Except as required by law, we assume no obligation to update forward-looking statements contained in this presentation, whether as a result of new information, future events or otherwise after the date of this presentation.

Finally, Ocugen's quarterly report on Form 10-Q covering the third quarter of 2025 will be filed today.

I will now turn the call over to Dr. Musunuri.

Thank you, Tiffany. Thank you all for joining us today. I'm pleased to share an update on our modifier gene therapy platform and would like to recognize that in just over 3 years, we brought our lead candidate, OCU400, from initial Phase 1/2 dosing to nearing Phase 3 enrollment completion.

The OCU410ST Phase 2/3 pivotal confirmatory trial is following close behind, and we are on track to complete enrollment in the first quarter of 2026, lining up for our planned biological licensing application, BLA submission, in the first half of 2027 for OCU410ST. This rapid progress is somewhat unheard of in the industry and not only reinforces our commitment to file 3 BLAs in the next 3 years, but it also brings us closer to addressing the incredible unmet medical needs that exist for patients facing vision loss.

While all 3 programs are moving along on schedule, we received additional, positive news in the third quarter that the Committee for Medicinal Products for Human Use, CHMP, of the European Medicines Agency confirmed the acceptability of a single U.S.-based trial for submission of MAA in Europe for OCU410ST. This alignment allows us to maintain the same timeline and budget efficiencies in Europe as we have with the OCU400 pivotal trials.

To fund clinical trial progress, we continue to pursue opportunities to increase our working capital and in August, closed the registered direct offering with Janus Henderson. The gross proceeds were approximately $20 million, which we anticipate will extend our runway through the second quarter of 2026, and we will receive $30 million of additional gross proceeds if the warrants are exercised in full, extending our runway into '27.

The OCU400 Phase 3 liMeLiGhT clinical trial remains on track for BLA and MAA submissions in 2026. It is the only broad retinitis pigmentosa RP gene-agnostic trial to address multiple genetic mutations with a single therapeutic approach. And it's important to note that this is the largest known Phase 3 orphan, gene therapy trial.

There are approximately 300,000 people in the U.S. and Europe combined living with RP, which affects more than 100 genes. Ocugen's gene-agnostic approach has the potential to treat multiple gene mutations associated with RP with a single, one-time, subretinal injection.

Currently, the only approved gene therapy for RP targets a single gene RPE65, which accounts for 1% to 2% of RP patient population. This product achieved peak sales of $52 million in 2023 with a patient population of approximately 2,000. We believe OCU400 has far greater commercial potential as it is intended to provide a therapeutic option for the remaining 98% to 99% of RP patients.

We anticipate commercialization in 2027. Process validation and manufacturing activities are progressing well in support of the BLA. Brand planning and marketing initiatives led by Abhi Gupta, our EVP of Commercial and Business Development, are scaling up as well. We will begin rolling submission of the OCU400 BLA in the first half of 2026 and release Phase 3 top line data in the fourth quarter of 2026, in line with our commitments.

As we prepare for what will ultimately be a global rollout for OCU400, we're pursuing regional partnerships that preserve Ocugen's rights to larger geographies to maximize total patient reach while also generating return for our shareholders. In September, we announced an exclusive licensing agreement with Kwangdong Pharmaceutical Company Limited for the rights to OCU400 in South Korea.

Under the agreement, the company will receive up to $7.5 million in upfront and development milestone payments plus sales milestones of $1.5 million for every $15 million of sales in South Korea, projected to reach $180 million or more in the first 10 years of commercialization. We will also earn a 25% royalty on net sales generated by Kwangdong and will be responsible for manufacturing and supplying OCU400.

There are an estimated 7,000 individuals in the Republic of Korea with RP, which represents approximately 7% of the U.S. market. OCU400 provides the opportunity for our partner to help thousands of patients facing vision loss. Upon regulatory approval of OCU400 in Korea, we believe Kwangdong will become a leader in the field of ophthalmic gene therapy in South Korea.

Now let's move on to OCU410ST. OCU410ST has the potential to target over 1,200 pathogen mutations in the ABCA4 gene associated with Stargardt disease and other ABCA4-related retinopathies with a single, onetime, subretinal injection.

As I mentioned earlier, enrollment in the Phase 2/3 GARDian3 clinical trial is ahead of schedule. The strong response underscores the significant, unmet medical need among Stargardt patients who currently have no approved treatment options available.

Stargardt disease affects approximately 100,000 people in the U.S. and Europe combined and approximately one million people globally. With CHMP acceptance of U.S. trial data for the MAA submission, we'll maximize resources and streamline development efforts with the goal of bringing OCU410ST to patients in Europe sooner than originally anticipated.

The 12-month data from all available Phase 1 subjects showed highly encouraging results with a 48.2% reduction in lesion growth and a meaningful online 6-letter gain in visual acuity in evaluable treated eyes compared with untreated eyes. All treated eyes also demonstrated stabilization or improvement in visual function, highlighting a consistent and tangible therapeutic benefit. Interim data from ongoing Phase 2/3 study is expected mid-2026, further advancing our goal of bringing OCU410ST to patients in need.

Finally, OCU410 is specifically designed to address multiple pathways implicated in the pathogenesis of dry age-related macular degeneration and offers a promising advantage for current treatment options that target only one pathway, the complement system, which does not fully address the disease progression and underlying causes of vision loss.

Currently approved treatment options require frequent intravitreal injections about 6 to 12 doses per year and are accompanied by various safety risks. For example, roughly 12% of patients develop wet AMD following treatment.

With approximately 2 million to 3 million geographic atrophy patients in the U.S. and Europe combined, OCU410 represents a significant market opportunity. Current therapies have notable limitations, and there are no treatments approved for GA in Europe, as existing FDA-approved options failed to demonstrate meaningful functional outcomes. OCU410 is therefore well positioned to address this critical, unmet, medical need.

At 12 months, available subjects in the Phase 1 study showed a 23% reduction in lesion growth, along with a 2-line or 10-letter stabilization or gain with visual equity in treated eyes. Preliminary results from 6-month interim analysis demonstrated a 27% reduction in lesion growth and preservation of retinal tissue in the treated eyes when compared to untreated control eyes.

This reduction is over twice that observed with currently approved, intravitreal therapies at 6 months, monthly and every other month PEG citicoline injections, which showed only 13% and 12% reductions, respectively, highlighting OCU410's potential to provide a significant and meaningful therapeutic benefit to patients with a onetime treatment.

In addition to the greater lesion reduction, a single subretinal injection of OCU410 demonstrates greater efficacy in preserving retinal tissue surrounding GA lesions compared with monthly and every other month PEG citicoline treatments. We plan to provide full 12-month data from the Phase 2 study, including both structural and functional outcomes, in the first quarter of 2026 and anticipate initiating the Phase 3 study next year.

I will now turn the call over to Ramesh Ramachandran to provide an update on our financial results for the quarter ended September 30, 2025.

Thank you, Shankar. The company's cash, cash equivalents and restricted cash totaled $32.9 million as of September 30, 2025, compared to $58.8 million as of December 31, 2024. With the recent $20 million financing in the third quarter, we believe our current cash position provides sufficient runway to operate through the second quarter of 2026.

Total operating expenses for the 3 months ended September 30, 2025, were $19.4 million and included research and development expenses of $11.2 million; and general and administrative expenses of $8.2 million. This compares to total operating expenses for the 3 months ended September 30, 2024, of $14.4 million that included research and development expenses of $8.1 million; and general and administrative expenses of $6.3 million.

That concludes my update for the quarter, Tiffany, back to you.

Thank you, Ramesh. We will now open the call for questions. Operator?

Your first question comes from the line of Michael Okunewitch with Maxim Group.

Congratulations on all the progress.

So, I guess to just start out, I'd like to ask a little bit about OCU400 and in particular the timing of the BLA completion. You mentioned that you are going to be starting that in the first half of 2026, enrolling BLA. But then how quickly do you believe that you can turn around the pivotal data over to the FDA and complete that filing?

As soon as it in, we're nearing completion as we stated. And we'll have resources ready to turn around in weeks.

All right. That's great to hear. And then in terms of your manufacturing, are there any other items that you need to do to get ready for commercial manufacturing before you can start submitting that and start the rolling BLA process?

Yes, good question. Our PPQ, our process validations runs, are going very well. They're on target. In fact, all the material we're making in support of the registration, they can be commercialized. So, we will have lots made ready to go.

And then just one more for me, and I'll hop back into the queue. For OCU410ST, with the upcoming interim readout, what endpoints are you expecting to release? Or is that going to be an internal DSMB review?

I mean for endpoint for the Phase 2, yes, it's already in the clinical protocol. We are looking at lesion growth compared to untreated control group. We do have untreated control group. And the secondary, we're looking at visual equity.

But I'm specifically referring to the interim release that you're expecting midyear 2026. Will that be publicly released or is that going to be internal?

That's a good point. Yes, there will be limited information publicly. The DMC looks at it, and then we'll be informing the agency. However, we will give some indications about the clinical trial.

I appreciate the update. It looks like there's a lot to look forward to Ocugen.

Your next question comes from the line of Boris Peaker with Titan Partners.

A couple of questions for me. Maybe let's start with the OCU400. Can you just remind us exactly what the statistical kind of design of the liMeLiGhT study is, what the assumptions were? And I'm just curious if you've had kind of recent discussion with the FDA to make sure that it's still acceptable. And I think this question comes in the context of what we've seen just recently with uniQure, where it sounds like the FDA may have moved the goalpost a little bit in their gene therapy. So, I think I just want to get a sense to make sure that similar dynamic doesn't happen here.

Yes. Good question. I'll start, then Huma will chime in.

So first and foremost, I want to distinguish all our clinical trials, including our Phase 2 GA trials, we have a control arm within the study. Typically, FDA -- that has been a tradition. Most of the clinical trials, FDA really looks for control within the study, not using some external controls or very rarely natural history. So I think I really want to differentiate that from what you mentioned about uniQure.

So, we do have our OCU400, OCU410ST total trials, including even OCU410 GA clinical trial, we have untreated control subjects in the clinical trial. So that's what we're using to compare.

And Huma, go ahead on the clinical trial design.

Yes. Thank you, Shankar. So, the clinical trial design is we have 150 subjects that we are planning to enroll for the study, 100 in the treatment and 50 in the control, 75 in the rhodopsin and 75 in the gene-agnostic arm with 50 being active and 25 in the control. We have 97% power for this study. We have assumed 50% and 10% treatment effect in the treated and the untreated eyes. And there is a 2:1 randomization, which means there is -- we are treating both the eyes as they meet the inclusion/exclusion criteria with the worst eye being dosed first. This is the only trial that is globally available with clinical and/or genetic diagnosis of RP with syndromic and covering non-syndromic forms.

And maybe a question on OCU200. You mentioned the milestone that we'll see completion of enrollment by the end of the year in Phase 1. Can you comment when we'll see the data? And what would that initial data include?

So we are on track for our OCU200 enrollment for our Phase 1. Our periodic safety updates are there. There are no serious adverse events related to the product listed as of right now. Yes, in the beginning of next year, we will be providing some more updates on the safety and efficacy of OCU200 as soon as it becomes available. But as this is a Phase 1 first-in-human, there are no serious adverse events related to the investigational product reported as of right now.

And how many patients will you have in that initial update?

So, we have a dose-ranging, dose escalation portion of the study. So, that would be almost 9 to 12 subjects.

Your next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

So, a couple of quick questions. The first one on OCU400, as you're nearing to the point where you're putting not only your application together, but also thinking about commercialization, what sort of investments are you making within the commercial infrastructure so that you're allocating appropriately within your budget for pre-commercial activities? Yes, let me start with that.

Yes. I think, I mean, based on 2027 launch next year, we will be ramping up slowly for U.S. commercialization. Obviously, our goal is to continue to look for partnerships just like we announced one in South Korea and other regional partnerships in Europe, Japan and elsewhere. But U.S., we are looking still into because it's a good market. We have a good handle. We created a lot of the centers for excellence, which will be part of the commercialization for subretinal delivery.

Therefore, we will have more information provided next year, but we'll slowly ramp up. We'll be allocating a carefully limited budget starting with. But we're looking into other revenues to beef that up next year.

Okay. And then on the ST, with the comment that it's reaching 50% enrollment on the GARDian3 trial, what's the cadence of enrollment there? Just trying to understand how the enrollment is going. Are there any geographies where you're seeing less of an enrollment? How many patients you're screening so that you get the enrollment moving?

Yes. I'll let Huma take that.

So, this trial includes 51 subjects, 34 in the treatment, 17 in the control. We are almost 50% and above in our enrollment. We have completed that, and we are on track. So, there are no geographical restrictions here. Actually, I would say, this is basically the disease of the pediatric population, and we are covering early to late stages of Stargardt, also 3 years of age and above. That's why we are pretty confident we are going to meet the enrollment goal. In fact, we do have almost half of what we have enrolled more than that in the screening queue.

So, we are on track for completion of our enrollment. But there is no geographic restrictions. There are almost 15 centers that we have equally covered across in the U.S. and all of them have the screening metrics for those patients as well. So, we are on track.

Shankar, if I may, can I ask one quick one on OCU400 itself? Having looked at the data from the earlier studies and the patient characteristics, have you folks identified any of the patients? Obviously, there are some who are high responders and some who are non-responders. In general, how are you thinking about what the real potential is for OCU400? And what could your commercial strategy be so that you try to get the highest adoption that you could get?

So RK, I mean, our design clearly outlines based on the strong scientific basis, we are targeting entire RP from early-stage to advanced pediatric to adult, and that's the coverage. And I mean, we are including in our Phase 3 clinical trial all major components of RP. That means some of the mutations with high prevalence rhodopsin or XLRP, [ RUSHERS ] and PDE6B, all those mutations are included with good representation.

So our goal is to look at the data holistic and get the broad RP indication, so that we provide a treatment potentially for all RP patients, not restricted to specific genotype.

Your next question comes from the line of Robert LeBoyer with NOBLE Capital.

Just as a follow-up from some of the previous questions, my understanding of OCU400 is that it's a regulatory gene that affects the entire gene network downstream, restoring homeostasis. So, early-stage, late-stage, child, adult, specific mutations really wouldn't matter because it's affecting the whole downstream pathway that leads to blindness. So please let me know if that is the correct way to think about it.

Yes, absolutely, Robert. You stated it.

Okay. And secondly, the OCU410 in GA is also ongoing. And could you just go over some of the endpoints and what to expect in that trial?

Yes. Huma?

So, we have completed our ArMaDa enrollment Phase 1/2. The Phase 1 was a typical dose-ranging, dose escalation, 3 plus 3 design, 9 subjects there. And also we had a Phase 2, where we had a high dose, medium dose and a controlled, which means that we enrolled 17 subjects in high dose, 17 in the medium dose and 17 in the controlled.

Also in terms of the endpoints in Phase 2/3, which is important, it's Stargardt atrophy lesion growth reduction from baseline and also looking at low luminance visual equity over the period of time as well, which is functional we have been consistently releasing the data on that, and we are on track for following up those patients until early part of next year.

So there is a 1-year time point, Robert, to clarify. Our GA trial is a 1-year trial.

Your next question comes from the line of Elemer Piros with Lucid Capital Markets.

So, Shankar, you talked about OCU410ST and your agreement -- OCU410ST, your agreement with the European agency that the U.S. trial would be sufficient. Do you have a similar agreement related to the RP program as well?

Yes. We have a similar agreement with [indiscernible], with EMA, on RP program.

Okay. And what would be the regulatory path in South Korea for OCU400?

Yes. Currently, it looks like South Korea and the rest of the world, typically for orphan gene therapies, they are following FDA closely. And once we get FDA approval, based on the FDA approval, we get approvals in those countries. So most of these countries don't need any additional clinical trials.

I understand. And one housekeeping question, how much of the $7.5 million or up to $7.5 million that you received from Kwangdong is included in the cash balance that you reported?

The $7.5 million is not included in the cash burn at this point of time. It is going to be in future. So that's not part of our cash burn at this point of time.

And could we project some into the fourth quarter in terms of the initial payment?

The $1 million, which we received from Kwangdong, that is already in the cash projection, but nothing more than that.

Okay, $1 million. Okay. And lastly, could you talk about your manufacturing capacity, Shankar, especially when we think about much larger indications such as OCU410 for geographic atrophy?

Yes. The manufacturing capacity, we have ex-U.S. partner with plenty of capacity. I mean, we have our own facility in our backyard in Malvern, Pennsylvania, and that facility will be ready. Our plan is to get that ready by 2027. And when we get the first approval, it's called a prior approval supplement with the U.S. FDA at the site. And our goal in future is to produce all U.S. supply from our U.S. manufacturing site.

But you mentioned also that you have an ex-U.S. partner as well, manufacturing partner.

Yes. That's right. Yes, currently. And we have plenty of capacity, global capacity.

Final question comes from the line of Daniil Gataulin with Chardan. Please go ahead.

First on OCU400, the trial, as we know, you have 2 arms, one with RHO mutations, one with RP gene-agnostic mutations. For the gene-agnostic arm, are you disclosing how many different mutations are included there? And in terms of the enrollment, did one arm see a more robust enrollment than the other?

Go ahead.

So actually, it's an assessor-blinded study. So, at this point, we cannot disclose. Gene agnostic means that all the major mutations will be covered, which is more than 95% geographically look at it in U.S. and globally. So we are going to cover that in the gene agnostic and all forms of rhodopsin are going to be in the rhodopsin arm. So that is the first one.

And yes, there is a robust enrollment randomization that we are proceeding with. As we stated, clinical and/or genetic diagnosis, syndromic, as well as non-syndromic forms.

In terms of prep for BLA filing for OCU400, what are the outstanding CMC -- or what is the outstanding CMC work that needs to be completed before you file?

Yes. With the RMAT designation, Daniil, we have opportunity to initiate rolling submission, as we stated, in the first half of next year. And so you can submit nonclinical and CMC sections. So, as far as CMC is concerned, we have to complete our process validation runs for drug substance and drug product, and it's progressing really well, and we're on target. So, those sections will be submitted before we submit the clinical section. That will be the last one late next year.

So somewhere in the middle of next year, somewhere we'll be submitting the manufacturing section. We'll start with nonclinical, followed by CMC, followed by clinical.

And one last question for LCA. Is that on hold for now or is that completely off or out of your pipeline? Or what are your plans for LCA?

From a market perspective, Daniil, it's very small. What we'll do is -- right now, it's not in our plan. And obviously, once the RP gets into the market, we can always look into that for Phase 4.

This concludes the Q&A portion. I will now turn the call back over to Chairman, CEO and Co-Founder, Dr. Shankar Musunuri. Please go ahead.

Thank you, operator. The third quarter was marked with important clinical progress, strategic business development and essential financing accomplishments. We are poised to close 2025 on a strong note and look forward to early 2026 catalysts that will further advance Ocugen's position as a biotechnology leader in gene therapy for blindness disease.

Have a great day. Thank you.

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