Ocugen, Inc.

Good morning and welcome to Ocugen's fourth quarter and full year 2024 financial results and business update. Please note that this call is being recorded at this time. All participant clients 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 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, OccuGen'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, will provide more detail on our financial results. And Dr. Huma Kumar, 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 of 2024. We encourage listeners to review this 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 investor 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 uncertainty. 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 preclinical and clinical development activities and related anticipated development 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 filing 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 speak 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 annual report on Form 10-K, covering 2024, will be filed today. I will now turn the call over to Dr. Musunari.

Thank you, Tiffany, and thank you all for joining us today. We are eager to share the ongoing progress of our novel modifier gene therapy platform across all three clinical programs. It was especially exciting to announce last week that we reached an alignment with the FDA to move forward with a Phase II-III pivotal confirmatory trial for OCU410SD BLA targeting Stargardt disease, making it possible to potentially expedite our clinical development timeline by two to three years, which is expected to save significant costs in addressing disease burden even sooner than anticipated. This important news also brings us closer to our goal of three potential BLAs in the next three years, OCU400 in 2026, OCU410-ST in 2027, and OCU410 in 2028. We know this is a bold ambition, but I'm confident that we have the strategic and scientific expertise, along with an unrelenting commitment to patients, to deliver on our commitment. During 2024, we continuously advanced our programs in line with enrollment and dosing timelines, and are continuing to drive the product pipeline forward in 2025. Throughout development, we are providing data to validate our revolutionary platform. To support our efforts in the clinic, we secured 65 million in equity and debt financings in the second half of 2024 that extends cash runway into the first quarter of 2026. Let's discuss OCU 400. our lead candidate in more detail. Retinitis pigmentosa affects 300,000 people in the U.S. and EU combined, and 1.6 million globally, and is associated with mutations in more than 100 genes. With only one product on the market that addresses 1% to 2% of patient population, you can see the ability for OQ400 to meet a tremendous unmet medical need and potentially capture all the market share through its gene agnostic mechanism of action. In February, the European Commission provided a positive opinion from the European Medicines Agency's EMA Committee for Advanced Therapies for OCU400 Advanced Therapy Medicinal Product ATMP Classification. ATMP classification is granted to medicines that can offer groundbreaking opportunities for the treatment of disease and accelerates the regulatory review timeline of this potential on-time gene therapy for life. Additionally, this classification allows oncogen to interact with EMA more frequently for scientific advice and protocol assistance. In January, we announced positive two-year safety and efficacy data from the OCU400 Phase 1-2 clinical trial that demonstrated clinically meaningful improvement of two-line gain, 10 letters on the ETDRS chart, in low luminescence visual equity, LLVA, in treated eyes when compared to untreated fellow eyes. This treatment effect was statistically significant, with a p-value of 0.005 in all subjects, regardless of mutation at two years, demonstrating the long-term durability for acute These two-year LLVA findings, which are the most sensitive measure of visual function, are consistent with the results observed at one year. The phase three study spanning one year will enroll 150 participants divided into two study arms, 75 participants with a row gene mutations and 75 participants who are gene agnostic. In each arm, participants will be randomized in a two-to-one ratio to receive either treatment, which is 2.5 times 10 to the 10 VGs per eye of RQ400, or remain in an untreated control group, respectively. We're actively enrolling patients in the U.S. and Canada in the Phase III Limelight Clinical Trial of RQ400 and intend to complete enrollment in the first half of 2025 to remain on track to meet BLA and MAA filings targets mid-2026. Next up is OCU410ST. With no approved treatments options available for patients with Stargardt disease, 100,000 patients in the U.S. and Europe combined are desperate for an answer. OCU410ST with a single subretinal injection has potential to treat Stargardt in all ABCA4-associated retinopathies, and in the fourth quarter received orphan medicinal product designation from the EMA for the treatment of ABCA4-associated retinopathies. Earlier this week, we announced that OCU410ST also received ATMP classification along with OCU410, which is a critical step to potentially address these severely unmet medical needs in the very near future. Six-month data from Phase 1 of the RQ410-SD Guardian trial demonstrated clinically meaningful two-line, 10-letter improvement in visual function measured by best corrected visual equity, BCVA, which is statistically significant with a p-value of 0.02 in treated eyes. 100% of evaluable treated eyes demonstrated stabilization or improvement in visual function. There was 52% slower atrophic lesion growth in Ocufort NST treated eyes versus untreated fellow eyes after single injection at six months in seven patients and 103% slower atrophic lesion growth in treated eyes versus untreated fellow eyes at 12 months in two patients. Ocufort NST maintains a favorable safety and tolerability profile with no serious adverse events. including no cases of ischemic optic neuropathy, vasculitis, intraocular inflammation, endothalamitis, or choroidal neovascularization, and no adverse events of special interest. The Phase 2-3 pivotal confirmatory trial of OQ410-ST will randomize 51 subjects, 34 of whom will receive a single subretinal 200 microliter injection of OQ-410ST at a concentration of 1.5 times 10 to the 11 vector genomes VG per ml in the eye with the worst visual equity and 17 of whom will serve an untreated controls. The primary endpoint in the clinical trial is change in atrophic lesion size. The secondary endpoint include visual equity as measured by best corrected visual equity and LLVA compared to untreated controls. One-year data will be utilized for the BLA filing. We plan to initiate the Phase II-III study mid-2025 and are targeting BLA submission by 2027. Now let's move on to our developments in OCU410, which is specifically designed to address multiple pathways implicated in the pathogenesis of triage-related macular degeneration and offer a distinct advantage over current treatment options that target only one pathway, a complement system. Currently FDA-approved treatment options require frequent intravitreal injections, about 6 to 12 doses per year, and are accompanied by various safety considerations. For example, roughly 12% of patients develop wet macular degeneration following treatment. It is also important to note there are no approved therapies for geographic atrophy, GA, in Europe. OCU410 has the potential to regulate all four pathways related to disease progression, lipid metabolism, inflammation, oxidative stress, and activation of the complement system, thereby addressing the underlying causes of this disease. Approximately two to three million patients in US and EU and 8 million patients globally suffer from GA, advanced form of DAMD. Preliminary 9-month data of Ocufortin showed clinically meaningful 2-line or 10-letter improvement in visual function, LLVA, and treated eyes compared to untreated eyes in the Phase I portion of the trial. Subjects showed considerably slower lesion growth, 44%, from baseline in treated eyes versus untreated fellow eyes at nine months and follow-up data from the phase one study. Preservation of retinal tissue at nine months around GA lesions of treated eyes with a single injection of Ocu410 in phase one compared favorably to published data on the leading FDA-approved complement inhibitor given monthly or every other month at the same time points. In the phase two study, the safety and efficacy of Ocu410 in patients with GA secondary to D-AMD will be assessed. 51 patients were randomized, one to one to one, into either of two treatment groups, medium or high dose, or a control group. In the treatment group, subjects received a single subretinal 200 microliter administration of five times 10 to the 10 vector genomes, or VGs per ml, which is a medium dose, are 1.5 times 10 to the 11 VGs per ml, high dose, while the control group remained untreated. This week, the DSMB convened and reviewed the safety and tolerability profile of an additional 15 subjects from the phase two portion of the study. No serious adverse events related to Ocu410 have been reported to date, in all 60 subjects, including phase one. Unlike currently available treatments for GA, there were no cases of ischemic optic neuropathy, vasculitis, intraocular inflammation, endothelmitis, or coroidal neovascularization, and no adverse events of special interest. Interim clinical data from the Armada clinical trial will be available in the second half of 2025. This data will help us design a future pivotal confirmatory phase 3 study planned for 2026 and enable our potential BLA and MAFI links as soon as 2028. Given the multifunctional effect of our modified gene therapy, the profound unmet medical need, limited treatment options, and the fact that it is designed as a one-and-done treatment, we believe RQ410 can be a potential gold standard for treating GA worldwide. Lastly, I would like to call attention to our biologic candidate and non-relation vaccines platform. OCU-200 moved into the clinic and patients are currently being dosed in phase one clinical trial for diabetic macular edema, DME. OCU-200 has the potential to change the treatment landscape for DME, diabetic retinopathy, and with macular degeneration, wet AMD. With its unique mechanism of action, binding the active component thumb statin to integrin receptors that play a crucial role in disease pathogenesis and holds the promise to benefit all DMA patients, including the 30 to 40% of patients who do not respond to current antivirgil therapies. The RQ200 Phase I clinical trial is a multicenter, open-level dose escalation study to assess drug safety via intravitreal injection in three cohorts, low-dose, 0.025 milligrams, medium dose, 0.05 milligrams, and a high dose, 0.1 milligram. All subjects will receive a total of two intravitreal injections of OCU-200 six weeks apart. Patients' follow-up will take place up to three months after the last injection. Approximately 12 million people in the United States, 130 million people worldwide are affected by DME, DR, are wet AMD. The investigational new drug IND application for OQ400, the company's inhaled mucosal vaccine for COVID-19, was cleared by the FDA. The National Institute of Allergy and Infectious Diseases, NIAID, part of the National Institute of Health, is expected to sponsor and conduct the phase one trial to assess the safety, tolerability, and immunogenicity for OQ400 administered via two different routes, inhalation into the lungs and intranasally as a spray. The phase one trial will enroll 80 adult subjects aged 18 to 64 years. 40 subjects will be assigned to the low dose group and 40 subjects will be assigned to the high dose group. Within each group, 20 subjects will receive the inhalation form of the vaccine and the other 20 subjects will receive the intranasal form. The primary aim of the study is to determine safety, while secondary and exploratory endpoints include antibody production, systemic as well as mucosal, and the number of breakthrough COVID-19 infections. OQ500 is based on a novel chimpanzee adeno-vectored CHAD36 technology. Earlier clinical studies to prevent COVID-19 that employed a similar technology administered by inhalation demonstrated increased mucosal and systemic antibodies and a durable immune response up to one year using one-fifth the dose compared to the same vaccine administered intramuscularly. The phase one clinical trial is anticipated to start in the second quarter of 2025. I'll now turn the call over to Ramesh Ramachandran to provide the financial update. Ramesh.

Thank you, Shankar, and good morning, everyone. I will now provide an overview of the key financial results for the fourth quarter and full year of 2024. Our research and development expenses for the quarter ended December 31st, 2024, were $8.3 million compared to $7.8 million for the fourth quarter of 2023. For the full year ended December 31st, 2024, research and development expenses were $32.1 million compared to $39.6 million for the year ended December 31st, 2023. General and administrative expenses for the fourth quarter ended December 31st, 2024 were $6.3 million compared to $5.2 million for the fourth quarter of 2023. General and administrative expenses for the year ended December 31st, 2024 were $26.7 million compared to $32.0 million for the year ended December 31st, 2023. Net loss was approximately $13.9 million or 0.05 cent net loss per share for the quarter ended December 31st, 2024, compared to a net loss of approximately $11 million or 0.04 cent per share net loss for the fourth quarter 2023. Full year net loss was $54.1 million or $0.20 cent net loss per share compared to a net loss of $63.1 million for the full year 2023, or $0.26 net loss per share. Our cash and restricted cash total $58.8 million as of December 31st, 2024, compared to $39.5 million as of year ended December 31st, 2023. We expect that our cash and restricted cash will enable us to fund operations into the first quarter of 2026. As always, we are proactively exploring shareholder friendly opportunities to increase our working capital, including partnerships that will drive long-term strategy for our scientific platforms. That concludes my update for the quarter. Tiffany, back to you.

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

We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. Our first question comes from the line of Michael Krutovich from Maxim Group. Please go ahead.

Hi there. Thank you guys so much for taking my questions today. Congrats on all the good progress. Thank you. I guess, first off, thinking about more of a housekeeping question, when thinking about your runaway, does this factor in for potentially newly launching studies like the ACCU410SP Phase 2-3?

Yes, Michael. It's already budgeted.

All right. And then I guess in terms of the – the DME program, right? Do you have an idea of when we could expect to see data start to emerge from that phase one, and then what sort of efficacy endpoints are being evaluated, just given that it is a phase one study?

Good morning.

I'll ask him what to address.

Good morning. Thank you for the question. Actually, we are looking at the safety and efficacy report of OCU 200 towards the end of this year. And as we are assessing the safety of unilateral intravectoral administration of OQ200, we're also looking at the exploratory endpoints of BCVA and the dose response of OQ200. However, we are also looking at the secondary endpoints of OQ200 antibody formation and PK of OQ200 as well.

Okay, thank you. And then just one more for me, and I'll hop back into the queue. Just for ACCU 500, right, I know this really hasn't been much of a core program lately, but just perhaps have you heard anything regarding funding availability for that Phase 1, just given that the recent uncertainty around funding we've heard of at NIH?

Yes, Michael. The NIAID had meetings with us, after our IND approval, and they're still stating they're on track to initiate the phase one.

All right. Thank you very much for the additional clarity, and once again, congrats on all the progress.

Thank you.

Our next question comes from the line of Swayam Pakula Ramakant from HC Raybright. Please go ahead.

Thank you. Good morning Shankar, Huma, and Tiffany. A couple of quick questions from me. So Shankar, you certainly have made an aggressive target for your team of filing three BLAs starting next year. So what gives you and your team confidence that you could achieve this? And as investors, what should we be watching out to see your progress towards these this goal?

Yeah, good morning. Okay, good question. I mean, investors need to look at our track record. We started most of the gene therapy programs getting into the clinic late 21, 22. And today we are in the beginning of 25. And we have all three programs running from all cylinders. So our track record speaks for itself. And so the goal is, once again, thanks to FDA, for allowing us to knock off the phase three and ability to convert existing phase two clinical trial into phase two three confirmatory portal trial for BLA for Stargardt disease. It's a significant medical need, and that naturally lines up. I mean, so we are estimating, if we start the trial mid-this year, about nine months of recruitment, and then it's a one-year follow-up that will put us into 27, and so that should be reasonably targeted for BLA. Similarly, getting into ARCA410, we recently announced a month ago that our recruitment is completed in our phase two clinical trial for ARCA410 targeting geographic atrophy. So that means our phase two will be completed by early next year. Our interim data, which is coming out in the second half of this year, will allow us to start having conversations and discussions with FDA as well as EMA on phase three clinical design. So we are hopeful to initiate that next year. Once again, that will have a one year duration. And GA is relatively easier to recruit compared to orphan diseases such as RP and Stargardt. And we are inundated with patients during our phase two clinical trial where so many patients reaching out to us. Therefore, that gives us confidence we can complete that clinical trial, including recruitment. If you start in 26, we can relatively get it done by 28, and that can be lined up for BLA. And so that's why I think these timelines are reasonable. So starting next year, RP, retinitis pigmentis RQ400, and 2027 is going to be RQ410ST Stargardt disease, and 2028, we're targeting BLA for RQ410 geographic atrophy.

Perfect. Thank you for that. So we are just talking about 410 for GA. So we know that there are two approved therapies for this indication. So given that, how easy would it be to convince both physicians and patients, you know, to initiate therapy on OQ410 as considering, you know, the price point differences?

Go ahead, Jima. Okay. Thank you for the question. I'll provide the clinical aspect and the price point. Shankar can provide the input. So, in terms of one of the things I wanted to mention here is that we completed recruitment ahead of time for GA because there was a huge, you know, number of requests from the patients who have already got SIFO-ray and ISER-ray. In fact, they were on the waiting list, and we had a certain number to recruit for our Phase III. In terms of whatever the approved therapies right now are there, particularly with competitors, the first and the foremost, in terms of the clinicians, the safety and tolerability profile of those products are concerning, and 12% of the patients are progressing to the wet AMD. In terms of the safety and tolerability profile of OcuPort 10, That gives us extreme confidence that there were no serious adverse events like CNV and ischemic optic neuropathy, endothelmitis, and vasculitis, which are the hallmarks of currently the approved products. Also, our protocol had included the washout period for those two approved products as well for a three-month period. So in terms of recruitment and in terms of the safety and durability and efficacy profile, we are not only seeing differences or improvements in the structural as well as the functional outcomes. And in Europe, there is no approved product. So most majority of the physicians, because of the compliance issues of 6 to 12 injections per year and safety considerations, are not really prescribing, and also the patients are reluctant to do that. As you see, the age mean onset is 60 years of age and older. And in terms of the price point, I would let Shankar add his thoughts here.

Thank you, Huma. So, Arke, from the price point perspective, as we stated, U.S. itself has more than a million patients with the late D-AMD, which is geographic atrophy, and most of these patients get potentially funded by CMS. So we need to start working with them. Obviously, as an organization, we are very mindful. We are watching other gene therapies, how they are getting priced. And unfortunately, in the marketplace, there are gene therapy products either today, either they're targeting very complex diseases, or they're going after ultra-rare diseases, or they're going after diseases that already have a solution in the marketplace. which is not an unmet medical need. It's using scientific platform AAV vector to deliver something to replace like one and done instead of taking multiple injections of biologicals or certain treatments. So definitely, we need to consider all the price points. And when you have a huge population like this, number one, the pricing should be reasonable. And it's a one and done treatment. So even the patients are mostly in 60s or 70s, they'll still have you know, many, many years of quality of life years, you know, remaining for them. So we'll do the appropriate pharmacoeconomic analysis and we will price it, you know, fairly so that, you know, our goal is to make sure the payers can, you know, reimburse it and the patients who really need the product, they get it. Our goal is to provide market access. We're going to work on every effort in our perspective to make sure our patients get our product. who need them.

Thank you. Thank you for that. So last question from me on OCCIE 400. With the Phase 3 program, with the Phase 3 study in progress, what additional data should we expect from the Phase 1-2 study, you know, between now and, you know, filing of your BLA next year?

So as we have recently updated on our durability profile as well as safety, so safety will continue to be there. That's a commitment that we have made. So also on the efficacy functional endpoints, we will continue to report the parameters accordingly, LLVA and other functional parameters as they become available.

Okay, the LLVA data we... recently announced at the two-year durability that's important, not only from payer perspective too. So we'll definitely have three-year data at the time of filing next year.

Perfect. Thanks for taking all my questions.

Thank you.

Question comes from the line of Robert LaBoyer from Noble Capital Markets. Please go ahead.

Good morning and congratulations on all the progress. My question has to do with OCU 500 and whether there will be any grant revenue to the company associated with the phase one trial.

Yeah, as we stated publicly, NIAID is sponsoring this program and we have completed our obligations from company perspective. We are responsible for doing all the preclinical work and manufacturing and filing the IND, getting it approved and cleared by FDA and then transferred to them. So we've done our part, and they're supposed to fund the Phase I clinical program and take it to the next level.

Okay. Will the funding be recorded as revenue by the company, or will this just be something where you turn it over to the agency and they run the trial?

Yeah, we'll be turning over to the agency there on the trial.

Okay, thank you.

Our next question comes from the line of Daniel Gattolin from Chargent. Please, go ahead.

Hey, good morning, guys. Congrats on all the progress. A couple questions on 410ST. First, what is your manufacturing strategy for 410ST, and do you plan on using the commercial-grade product for the Phase 2-3 study?

Good question, Daniel. We already made, at a commercial scale, introduced into our Phase 1, and the same scale will be used for Phase 2-3. We'll follow the similar pattern like we're doing for RP. For RP, we're introducing two commercial-scale lots In our pivotal trial, we'll do the same thing for SD program, which is consistent, and FDA agreed with our strategy, and we're moving forward with that.

Okay, got it. And in terms of the sites for this study, are you looking at both ES and XES sites, and what are the proportions of each, if you're using both?

There is no XUS sites except for Canada, of course. I mean, we do have sites set up in Canada for retinitis pigmentosa. If necessary, we'll activate those sites for Stargardt. But based on the patient population, we only need 51 patients. I think Huma and her team are comfortable that they can get those patients in the U.S. very quickly.

Got it. Okay, thank you very much for taking the question. Thank you.

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. We appreciate the continued interest and involvement of our key stakeholders as we move forward with our transformative initiatives. We look forward to a year of significant catalysis. ahead as we establish Ocogen as the pioneering biotechnology leader in gene therapies for blindness diseases. Have a great day.