Ocugen, Inc. Q4 FY2025 earnings call

Dr. Shankar Musunuri highlighted that 2025 was a transformative year for Ocugen with development across modifier gene therapy programs, including licensing and financing agreements, and leadership team appointments. The Phase 3 Limelight clinical trial for OCU400 (modifier gene therapy for RP) has completed enrollment, with top-line data expected in 2027 to support BLA filing. Positive long-term Phase 1/2 data for OCU400 show sustained benefit. OCU410ST for Stargardt disease has positive Phase 1 results and received Rare Pediatric Disease designation. Ellipsoid zone analysis is an exploratory endpoint in clinical trials. OCU410 for GA secondary to late-stage dry AMD had positive preliminary 12-month data. Other programs: OCU200 enrollment expected to complete in 2026, NIAID intends to initiate Phase 1 for OCU500 in 2026, and Arthroselix was created as a subsidiary. Executive leadership team was strengthened. Rita Johnson Green provided financial results: Q4 2025 R&D expenses $10.7M vs $8.3M in 2024, G&A $6.1M vs $6.3M; full year 2025 R&D $39.8M vs $32.1M, G&A $27.6M vs $26.7M. Cash runway extended with recent raises.

2026 represents multiple inflection points including completion of OCU410ST enrollment in early 2026, full Phase 2 data for OCU410 this month, interim pivotal data for OCU410ST in Q3, initiation of Phase 3 for OCU410 in 2026, and start of rolling BLA submission for OCU400 in Q3.

Q: 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 endpoint to actually releasing the top-line data within first quarter 2027?

A: We are very confident that we will be able to hit our timeline.

Q: Could you remind us of some of the modifications that you made for that particular navigation assessment course and why you decided to go with it as a primary metric for RP?

A: In terms of the mobility test that we are using, proprietary to Ocugen, Inc., that is luminance-dependent navigation assessment (LDNA). It is the mobility test that was approved as the primary endpoint for Luxturna; that was called MLMT at that time. This is a very sensitive and specific test. This was also aligned with FDA, a validated test, as well as this was approved by FDA, and the only test that can capture the real change with functional outcome, demonstrating the functional outcome in these mutations.

Q: For the Stargardt program, it is looking like there could be an approval from another company for a chronic therapy by the time you file for OCU410ST. So I wanted to know how this might impact the opportunity or pricing potential and if there is any reason that OCU410ST could not be complementary with other therapies as they come to market?

A: There are other therapies out there. Obviously, what we have shown—if you look at the data we published in Eye—in one year, again, I want to restate all our trials were able to show treatment benefit in one year, unlike other trials out there of two years or more. The data we showed in one year are compelling. It looks superior. Our goal is to show functional benefit. With the gene therapy, we are targeting the major pathways, which are complex in Stargardt and GA. With our modifier gene, we also have the ability to reset the homeostasis and create a healthy environment for retinal cells to survive. That is very important. We are not just trying to slow down the disease progression. Our genes have the ability to control the internal network, so there is a big difference. Also, this is one-and-done. If you have a one-and-done therapy, this will set the standard of care. We are not worried about other therapies if they come to the market first. It is good—those therapies will educate the market and create market education. We may be behind them, but it is okay, because we believe we are going to set the standard of care for Stargardt patients globally.

Q: For the RP OCU400 rolling BLA, when would we get the FDA feedback on your CMC part of the filing?

A: Typically, the CMC will be filed this year. Obviously, FDA has the right to request comments before, or they will wait for the entire BLA to be filed. Even though they are internally reviewing, you may not expect anything before the actual final clinical module is filed.

Q: Have you discussed the ellipsoid zone as an endpoint with the Agency? I am just curious what their thoughts are about it as maybe 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 general thoughts on that endpoint?

A: Ellipsoid zone—obviously, as we stated before, in all our clinical trials we are trying to show benefit because the diseases we are targeting have significant unmet medical needs. More delays and doing longer trials will take not only the resources from our perspective; it is not doing benefit to the patients. If you are able to show a benefit using primary endpoints we picked, which are acceptable, the EZ will be a secondary and some other analyses just to further support that we are demonstrating a good functional outcome or related to functional outcome. That is important. If you do longer trials, like two or three years, sure, we can look into multiple options. From FDA's perspective, they really focus on the primary endpoint. If you hit the primary endpoint, you will get the approval. If you hit the secondary, yes, you can include it in the product insert and the label. However, remember, in all our clinical trials, we have an obligation to continue them for five years for safety monitoring. That means one-year data are needed for filing. After that—second year, third year, fourth year, fifth year—we monitor the patients. We will continue to monitor them with these secondary endpoints. At any point the data are supportive, we can always add it to the label. From FDA's perspective, you have to hit the primary endpoint to get the product approved. Secondary is not necessary for approval. If you hit it, it is good; you can put it in the label.

Q: Looking into the OCU410 program, in the Phase 2 study, the medium dose showed a 54% reduction versus the high dose, which showed a 36% reduction. I am trying to understand, as you go into your Phase 3 study, what is going to impact your decision for dose selection? Also, do you think that between these doses you are actually seeing some sort of a plateau effect in the transgene expression?

A: The data we released—obviously, the high dose had fewer numbers in there. I would wait until we get the complete dataset this month to make an inference. From the Agency's perspective, if the lower dose is showing equal or better effect, you would take that into Phase 3. That is standard practice. I suggest we wait. Typically, for our genes—and what we have seen in our RP studies too—these genes require a threshold. Once you hit the threshold, we did not see any dose response. We are going to evaluate carefully once we get the full dataset.

Q: In the subpopulation where the baseline lesions were greater than or equal to 7.5 mm², you saw a 57% reduction in lesion growth. As you get into the Phase 3 study, would you have any restrictions in terms of the size of the lesions, or do you plan to use the same criteria as in Phase 2, which was all comers?

A: That is a good question. This is why we do Phase 2. We are going to carefully evaluate. We go from 2.5 to 22 mm², and we are going to evaluate and see. On the lower side, as you know, analytically, you will have more variability. Of course, we are going to look at where the average patients fall, even though in the larger trials people have done with a lot of data. We are going to look at all those metrics and see what is the right group to go into Phase 3.

Q: The last question from me is on the OCU410ST program, where you are expecting to get the enrollment done this quarter and put up some interim data in Q3. In that dataset, what are we really looking for which can give us some indication of how the 2027 BLA filing is going to go, especially signals on either the structural side of things or on the functional side of things? What do you weigh more, and how should we be thinking when the data come out?

A: In terms of the masked interim analysis that is coming later part of the year, it will be for 24 subjects—16 treatment and 8 in the control. This is the adaptive design; that is a unique approach we have taken. The data points we are going to present, as we have presented this morning as well, are the primary endpoint—the lesion growth reduction—as well as structural and functional outcomes, which include visual acuity. We are also looking into the ellipsoid zone, which is the functional outcome that is very unique, and that data were very well received from the Stargardt perspective that we recently presented at one of the conferences as well. We are going to look at 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. This is what we are looking to release as masked interim analysis for those subjects later part of the year.

Q: What would be a clinically meaningful improvement? Where do you draw the threshold toward that?

A: As we said, it is a change in lux level improvement from baseline. There are a lot of mutations we are looking into. LDNA—luminance-dependent navigation assessment—is a validated protocol. That is what we are aiming for, and that is what our analysis is going to be based on. As I said earlier as well, there is a lot of heterogeneity with clinical diagnoses, and syndromic and nonsyndromic forms. The clinical meaningfulness is greater than or equal to one lux level.

Q: What are some of the secondary endpoints that you would also look at to support that primary?

A: The secondary endpoints are visual acuity, low-luminance visual acuity, and patient-reported outcome scores. We will be looking into these, and that is very well agreed and aligned with the FDA.

Q: Are both eyes treated? Could you remind us?

A: Yes, that is correct. Yes, if both eyes meet the inclusion/exclusion criteria, both eyes are treated. It is a 2:1 randomization, a single subretinal injection, and the control group will have a crossover after one year.

Q: For dry AMD, you mentioned a 50% responder rate. Were there any underlying characteristics that made a patient more likely to be a responder?

A: Are you talking about OCU410 GA? Yes. In terms of the responder rate, we have the inclusion/exclusion criteria, which were very uniform across the groups. Baseline characteristics included the mean age—we were looking at GA diagnosed at a certain age, with the mean in the mid-70s. We were also looking at the lesion size, which is pretty much well-versed with the OAKS and DERBY trials that Apellis got approval on—7.5 mm² was the mean, up to 8.03. In terms of the baseline characteristics, the responders responded on the medium dose as well as on the high dose. There was not really any other unique criterion that we would cite at this point until we get our final clinical study report. At this point, it seems like it was uniform across all dose groups.