Ocugen, Inc. (OCGN) Earnings Call Transcript & Summary

Good morning. My name is Rob, and I will be your conference operator today. At this time, I would like to welcome everyone to the Ocugen Inc. Business Update Conference Call. [Operator Instructions]. Thank you. Tiffany Hamilton, Head of Communications you may begin your conference.

Thank you. Good morning. Earlier this morning, we issued a press release announcing a positive clinical study update for safety and efficacy results from our Phase I/II trial of OCU400 for modifier gene therapy product for the treatment of retinitis pigmentosa and Leber congenital amaurosis. 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 of 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, including, but not limited to, statements regarding qualitative assessments of available data, potential benefits, expectations for ongoing clinical trials and anticipated timing of clinical trial updates and regulatory interactions. 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 are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from our current expectations, including, but not limited to, the risks of preliminary interim and top line clinical trial results may not be indicative of and may differ from final clinical data. The favorable new data trial may emerge in the Phase I/II clinical trial for further analysis of existing clinical trial data. That earlier nonclinical and clinical data and testing may not be predictive of the results or successes of later clinical trials and the clinical trial data are subject to different interpretations and assessments. These and other risks and uncertainties are more fully described in the periodic filings with the Securities and Exchange Commission, SEC, including 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 date of this presentation. Except as required by law, we assume no obligation to update forward-looking statements contained in this presentation, whether results of new information, future events or otherwise after the date of this presentation. I'll now turn it over to Ocugen's Chairman, CEO and Co-Founder, Dr. Shankar Musunuri.

Thank you, Tiffany. Good morning, everyone. We're excited to share clinical study updates on safety and efficacy results from the Phase I/II clinical trial of OCU400, and now well modifier gene therapy product candidate for the treatment of retinitis pigmentosa or RP and Leber congenital amaurosis or LCA. Joining me today to provide data and safety updates from the OCU400 clinical trial are Dr. Arun Upadhyay, Chief Scientific Officer, Head of Research, Development and Medical Ocugen and Dr. Huma Qamar, head of Clinical Development and Medical advice Ocugen. We are honored to also be joined by Dr. David Birch, Scientific Director, Retina Foundation of the Southwest and principal investigator of the study; and Dr. Byron Lam, Mark J. Daly Professor, Baskin Palmer Institute, University of Miami, Principal Investigator of the study; Dr. Lejla Vajzovic Associate Professor of Ophthalmology with Tenure, Director of Duke vitreoretinal fellowship program at Duke Eye Center and Duke University School of Medicine and a leader in gene therapy research. Dr. Birch, would you like to comment on RP and LCA and what patients with these conditions are hoping for?

Yes. So I'm delighted to. I'm excited about this program. We have about 10,000 people globally that have mutations in the adoption gene and several thousand that have LCA. And we're looking for any kind of treatment that will hopefully slow the progress and stabilize the condition. And I think the preliminary data is very exciting, and we would consider this as a major benefit if we could somehow slow this down and maybe even improve division a little bit.

You have been a principal investigator on this trial for almost 2 years. What have you seen in this trial to date?

Well, we've been very impressed by the safety profile. We've really not had any serious adverse events at our sites. And the patients that we have treated have responded well to the treatment, and we're seeing some evidence of stabilization.

Thank you, Dr. Birch. It is very gratifying to see continued positive trends in the preliminary results from our novel modifier gene therapy approach. This is the first clinical validation of the platform where patient responses across various genetic mutations support our belief that OCU400 has the potential to transform the lives of many patients who are struggling with the debilitating blindness diseases. Let me give you a quick refresher on what gene modifier therapy is. Modifier gene therapy is designed to fulfill unmet medical needs related to retinal diseases, including IRDs such as RP, LCA and Stargardt disease as well as dry AMD. Our modified gene therapy platform is based on the use of NHR, massaging regulators, which have the potential to restore homeostasis, the basic biological processes in the retina. Unlike single gene replacement therapies, which only target one genetic mutation, we believe that our modifier gene therapy platform through its use of NHRs represents a novel approach that has the potential to address multiple retinal diseases caused by mutations and the multiple genes with one product and to address complex diseases that are potentially caused by imbalances in multiple gene networks. Currently, Ocugen has 3 modifier gene therapy programs. OCU400 for RP and LCA, which affects approximately 125,000 patients in the U.S. living with any of the 125 gene associated mutations. OCU410 for dry age-related macular degeneration, a disease affecting 10 million people in the U.S. alone, and OCU410ST for Stargardt disease an orphan disease affecting 35,000 Americans. I'm now going to hand it over to Arun, who will provide more detail on the clinical study for OCU400 Phase I/II trial results. Arun?

Thank you, Shankar. I would like to start with the highlights of the call by providing the major clinical development milestone for OCU400 program. We dosed the first patient in the study in March 2022 and completed the 3 plus 3 dose [indiscernible] phase, enrolling 10 subjects by November 2022, followed by the open enrollment phase, which enrolled 8 subjects and was completed by March 2023. We announced a positive preliminary data update on April 14 this year. The DSMB meeting held on April 18, 2023 voted unanimously to continue enrollment for adult CEP290 and pediatric RP and LCA patients. We are now announcing a second positive clinical study update from this Phase I/II trial. During today's call, we will be sharing an overview of OCU400 gene therapy platform, discuss the investigational product mechanism of Axon in brief, our clinical program, including a study endpoint inclusion decision criteria in brief, safety summary update, overall responder analysis followed by a study conclusion and key takeaways from this study update. As you are aware, the FDA granted orphan drug designation for all retinitis pigmentosa and Leber congenital amaurosis mutation for OCU400 drug product. These 2 DGs have a worldwide prevalence affecting approximately 1.6 million patients. The current treatments and treatments in development for RP are focused on addressing a specific gene mutation and developing a therapy for over 125 mutation that cause RP and LCA could be a daunting task. To address this outcomings of current therapeutic landscape, we developed a broader spectrum, novel gene agnostic approach to genetically diverse retinal diseases with a single sub retinal injection using Nr2e3 nuclear hormone receptor gene that has the potential to either pressure, improve or restore the retinal function in digit condition. Modifier gene therapy is a novel approach to treat genetic and complex multifactorial diseases. Unlike traditional gene editing or the placement therapy in this approach, we deliver a functional copy of a modifier gene such as Nr2e3 in the case of OCU400 to the target retinal cells. Preliminary data have shown that OCU400 rescues retinal degenerates and in multiple mouse models of retinitis pigmentosa and Leber congenital amaurosis by modulating nuclear hormone receptors and restoring cellular homeostasis. Overexpression of modifier gene NR2E3 can result in more [indiscernible] promote photoreceptor survival and can improve visual outcomes. We believe this approach has potential to address multiple genetic defects with single product utilizing a gene agnostic approach. Safety was the primary objective of this Phase I/II study, where the safety of drug product and subretinal administration on were evaluated. Additionally, we also looked at immune response and systemic distribution. Multiple readouts, indicative of structural and functional changes were monitored as a part of exploratory efficacy measurements. In this study update, we will be focusing on best-corrected visual acuity that is BCVA, low-luminance visual acuity, that is LLVA and multi-lumen mobility test, MLMT measurement, which are used to gauge visual function and functional vision in patient. As a part of the inclusion exclusion criteria, a confirmed diagnosis of Nr2e3 or CEP290 mutation and BCVA score of less or equal to 25.50 for RP subjects and [indiscernible] 3.5 based on scenario chart for LC subject, while the primary inclusion criteria. Exclusion criteria for the study included previous treatment with gene or cell therapy product, any contraindication of subretinal injection, like of outer nuclear layer for RP patients and involvement of central nervous system that impact visual function of LCA subjects. More details about the endpoint and inclusion exclusion criteria and their description can be found on [indiscernible] site. We enrolled a total of 18 subjects in the dose escalation and dose expansion phase of the study, which consisted of 10 row subjects 5 out of summer recessive Nr2e3 subjects and 3 autosomal dominant Nr2e3 subjects. All the subjects received a single subretinal injection predominantly localized to the center region of the retina. Few subjects received injection in the central temporal or superior temporal regions. We are currently enrolling adult LCA with the CEP290 mutation and the pediatric RPLs subject in this study, which is expected to be completed by this year. The Phase I/II clinical trial demonstrated that OCU400 continues to be generally safe and well tolerated in subjects across different mutations and dose levels that is low, medium and high dose levels tested in this study. No serious adverse events related to the investigational product were found in low and medium dose cohorts. In the high dose and open enrollment cohorts, SAEs were reported for 2 subjects that were not related to the study drug. The adverse events were mostly dimmed related to the surgical procedure and resolve within a few days to weeks. As you all know, both RP and LCA are a group of inherited heterogeneous genetic disorders that affect retina and eventually can lead to the blindness. So therapeutic targets should primarily focus on achieving a stabilization of the vision or slowing down the disease progression and eventually improving the vision in the patient as a means to benefit this RP and LCA patients. As a part of efficacy assessment, we evaluated the response to the study drug in subjects who have completed a minimum of 6 months post OCU400 dodging by assessing improvement in the best correct individual equity that is BCVA at 4 or more letters and 7 or more letters from the baseline. We also looked at improvement in low luminescence vision acuity score at equal or more than 5 letters and equal or more than 10 letters from the baseline. And we also looked at the changes in the MLMT test at different lux level that is equal or more than 3 lux levels equal and more than 1 lux level of improvement or stabilization that is no change in the lux level, demonstrating stability. A lot of subjects in these trials also sold the ceiling effect, which can be defined when a subject passage MLMT test at the highest lux level that is at the lowest limit of rementions intensity, which was 1 lux in the start to begin with. To overcome and further widen the range of this test, we have further increased the sensitivity of this assay and included another light level that is 0.1 lux level in the measurement, which we will be collecting data on the upcoming assessment for remaining subjects. Here, we wanted to show in this venn diagram to demonstrate that out of 12 subjects showed either a stabilization, which we define no change from baseline, which is defined as plus/minus 3 liter change for BCVA and LLVA is considered as a stabilization and the zero left level change for MLMT or improvement in all 3 parameters for BCVA and LLVA was defined as any change, which is 4 or more letters improvement and formal MT, 1 lux level or more were considered as improvement to demonstrate the efficacy of OCU400. Nonresponders for each parameter set also an outside the circle for each group. Overall responder analysis for all these 3 efficacy end points is presented here in paragraph that is BCVA, LLVA and LMT. Regions from the treated eyes are shown in green and untreated eyes are shown as orange. As you can see on the BCVA, 42% of subjects showed 4 or more letter of improvement, whereas 33% subjects showed 7 or more letters of improvement in BCVAs scores from baseline. When you look at the LLVA that middle panel, 42% of subjects showed 5 or more later improvement, whereas 25% subject showed 10 or more letter of improvement in LLVA score from baseline. In MLMT 33% of subjects showed one or more lux level improvement, whereas 17% subjects showed 3 or more or less level of improvement from the baseline. So in summary, overall, OCU400 demonstrated a favorable safety and tolerability profile. Our clinical study suggest positive trends in BCVA, MLMT and LLVS cores. The key efficacy outcome from the 12 subjects demonstrated 4 key points. 83% of subjects demonstrated preservation or improvement in the treated eye, either on BCVA or LLVA or MLMT scores from the baseline. 75% subjects, that is 9 out of 12 demonstrated a stabilization or improvement in treated eyes in MLMT score from baseline. In low mutation specifically, 86% subject, 6 out of 7 experienced either stabilization or infusion MLMPs score from baseline, among which, 29% subject demonstrated 3 lux level -- lux luminescence level improvement. This effect in the low patient supports the gene-agnostic mechanism Axon of OCU400. As you all know, OCU400 product is the Nr2e3 best nuclear hormone receptor modifier gene whereas the raw mutation is the unrelated gene. So the key takeaways from this study is that the clinical study data reserves from patients treated in the Phase I/II clinical trial are very encouraging and support the paradigm-changing potential of modifier gene therapy technology to address unmet medical needs for patients with RP and LCA. With this favorable safety profile and continued positive improvement in BCVA LLVA, MLMT signal in the study participants. We would like to thank the study investigators, study participants, site coordinators and the research team at Ocugen for their continued hard work to take this program to the next level in the development. Thank you. Now I will hand over to Shankar.

Thank you, Arun. As I had mentioned at the beginning of the call, the next gene therapies we intend to bring into the clinic are OCU410 for geographic atrophy, which is part of dry-AMD and OCU410ST for Stargardt disease. We intend to initiate Phase I/II trials for both these programs by the end of 2023. With OCU410 and OCU410ST, we believe we have a potential onetime [indiscernible] therapy with a single injection. We are inspired by the opportunity and the responsibility to develop therapies with the potential to improve health, offer hope and even change the lives of patients. They deserve better. They deserve our best. Operating and the service of patients means we let our passion, dedication, commitment and compassion lead us in developing therapeutics that give people new options for healthier and better lives. Ocugen's mission and vision is to address unmet medical needs and to develop a potential cure for blindness with courageous innovation. Dr. Lam, please share your perspective from the Phase I/II trial in your clinic.

Well, I think what is important is that, as mentioned, this is a great unmet need. So there are no proven treatment. And I would have to say our experience with this treatment based on the preliminary result is that this treatment can go further testing. And that the data that's collected in Phase I/II really helps in terms of designing a Phase II or a Phase III clinical trial. So I do feel that this approach is also very novel and somehow genetically agnostic that sort of not for one particular genotype. So I do think that there is a potential here for further studying regarding modulation.

Thank you, Dr. Lam. Dr. Lal, what are your final thoughts regarding safety and efficacy of the study.

Yes. Thank you. It's a pleasure to join you all this morning and super excited about this preliminary results. As a retina surgeons who has been involved in quite a few clinical trials over the years and leading some of the gene therapy trials that are currently in IRD space and common retinal diseases based I'm truly excited about these preliminary results. Why am I excited? I think, first of all, as a Phase I/IIa, we're answering the question of safety. I think the results show that this product is safe. And in addition to safety, we actually see external preliminary efficacy results with improvement in visual acuity. We all know that there's no treatment for this disease currently. I am truly excited to see our safe approach to addressing this disease in these preliminary results, but we may even see positive results in terms of efficacy. And I think that's kind of a icing on the cake with this trial that really is designed for safety, so truly excited.

Thank you Dr. Lejla. Now we'll open the webcast for questions.

[Operator Instructions] And your first question today comes from the line of Jennifer Kim from Cantor Fitzgerald.

Maybe 2 for the team and then one for the doctors. My first question is I wasn't sure based off the language of the press release, but is your intention for the pivotal trial to pursue patients specifically with Row mutations? Or what's the strategy there? And then my second question is in those patients that maybe have not yet reached 6 months on trial, could we see updated data in those patients? And have you seen any responses in those patients as well? Thanks.

Thanks Jennifer. Yes. So our plan is to not only include row but multiple mutations, okay, based on this study. And regarding like study update for remaining subjects still we have to wait for the data. Yes, minimum 6 months, yes.

Okay. And when could we get that data?

Depending on like when we complete the 6-month visit, and we complete the data lock. So it may take some time, but I would say probably like early next year. But in between, like, we'll continue to monitor as we collect the data.

Okay. And then a question for the investigators and doctors. Just in terms of these patients, when you're looking at the MLMT and LLVA test, what do you consider clinically meaningful? Because I know Luxton, they were looking at a median of at least 2 lines of improvement on MLMT but I'm just wondering what your thoughts are on these different tests. Thanks.

Dr. Birch.

I'll jump in there and say that personally, I can say anything that's above the repeat variability of the test is meaningful to me. So in terms of visual acuity, certainly, 5 or 6 lines is very meaningful. I know that the FDA is a lot more conservative and they -- for their pivotal trials, they often like 3 lines, but that's probably not going to be reached by [indiscernible] trials. And I think we're sort of working with the FDA to moderate their requirements.

Okay. And then do you have [indiscernible]?

I mean other tests yes. Yes, we don't have as much data on the mobility course. But certainly, a change in 3 levels is highly meaningful.

And your next question comes from the line of Li Chen from H.C. Wainwright.

This is Li Chen [indiscernible]. Congratulations on the positive results. I have a couple of questions. One is, have you measured the controllers, how they respond? And the second question is, can you give me -- can you please give us your understanding of the genetic profile of those responders. Yes?

Yes. Thanks. So yes, we did look at the controlled little eye. And if you look at the bar graph we presented, you can see that we have both data for both treated and untreated eyes. So yes, controlled little eye has been monitored. And could you repeat your second part of the question?

The second question is the genetic profile of the neuro responders.

Yes. So we looked at it, it is like mixed disease across. So it is not like mutation specific, but -- and still, we need to collect a product call longer-term data for all these mutations in order to make that determination whether there is any correlation between mutation and the treatment outcome. But so far, we are not seeing that. But one thing definitely, we would like to mention that the patient at very advanced the stage like some of the sentinel subjects, their response will be minimum compared to the patient who has like a preserved photoreceptor or you can say, less degenerated retina, okay, you expect better ratification outcome.

[Operator Instructions] And there are no further questions at this time. I will hand the call back over to Shankar for some final closing remarks.

Thank you. Thank you all for joining us this morning. We are excited about the future as in store for Ocugen and the patients we aim to treat. Have a great rest of your week. Thank you.

This concludes today's conference call. Thank you for your participation. You may now disconnect.