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. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. 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, a 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 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 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 that, preliminary, interim, and top-line clinical trial results may not be indicative of and may differ from final clinical data. In favorable new data trial, data new may emerge in the phase I/II clinical trial or further analyses of existing clinical trial data.
That earlier non-clinical and clinical data and testing may not be predictive of the results or successes of later clinical trials, and that clinical trial data are subject to differing 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 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. 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, a novel 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 Affairs, 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. Daily Professor, Bascom Palmer Eye 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 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, I'm delighted to. I'm excited about this program. We have about 10,000 people globally that have mutations in the rhodopsin gene and several thousand that have LCA. And you know, we're looking for any kind of a treatment that will hopefully slow the progress and stabilize the condition. I think the preliminary data is very exciting. We would consider this a major benefit if we could somehow slow this down and maybe even improve the vision a little bit.
You have been a principal investigator on this trial for almost two 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 site. And the patients that we have 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 blinding 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 modifier gene therapy platform is based on the use of NHRs, master gene 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 in the multiple genes with one product, and to address complex diseases that are potentially caused by imbalances in multiple gene networks. Currently, Ocugen has three 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 + 3 dosage escalation phase, enrolling 10 subjects by November 2022, followed by the open enrollment phase, which enrolled eight subjects and was completed by March 2023. We announced a positive preliminary data update on April 14th ththis 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 action in brief, our clinical program, including a study endpoint, inclusion/exclusion criteria in brief, safety summary update, overall responder analysis, followed by 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, amaurosis mutation for OCU400 drug product. These two disease 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 mutations that cause RP and LCA could be a daunting task.
To address the shortcomings of current therapeutic landscape, we developed a broader-spectrum, novel, gene-agnostic approach to genetically diverse retinal diseases with a single subretinal injection using NR2E3 nuclear hormone receptor gene, that has the potential to either preserve, improve, or restore the retinal function in this condition. Modifier gene therapy is a novel approach to treat genetic and complex multifactorial diseases. Unlike traditional gene editing or replacement 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 degeneration 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 molecular reset, 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 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 sub study update, we will be focusing on best corrected visual acuity, that is BCVA, low luminance visual acuity, that is LLVA, and multi-luminance mobility test, MLMT measurement, which are used to gauge visual function and functional vision in patient. As a part of key inclusion/exclusion criteria, a confirmed diagnosis of NR2E3, RHO, or CEP290 mutation, and BCVA score of less or equal to 20/50 for RP subjects, and logMAR of 3.5, based on Snellen chart for LCA subject, was the primary inclusion criteria. Key exclusion criteria for the study included: previous treatment with gene or cell therapy product, any contraindication of subretinal injection, lack of outer nuclear layer for RP patients, and involvement of central nervous system that impact visual function of LCA subjects. More details about the endpoints and inclusion/exclusion criteria and their description can be found on ClinicalTrials.gov website.
We enrolled a total of 18 subjects in the dose escalation and dose expansion phase of the study, which consisted of 10 RHO subjects, five autosomal recessive NR2E3 subjects, and three autosomal dominant NR2E3 subjects. All the subjects received a single subretinal injection, predominantly localized to the central 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 RP and LCA subject in this study, which is expected to be completed by this year. The phase I/II clinical trial demonstrated that OCU400 continued 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 two subjects that were not related to the study drug. The adverse events were mostly deemed related to the surgical procedure and resolved within few days to weeks. As you all know, both RP and LCA are a group of inherited heterogeneous genetic disorders that affects retina and eventually can lead to the blindness. So therapeutic targets should primarily focus on achieving a stabilization of the vision or slowing, slowing down the disease progression, and eventually improving the vision in the patients as a means to benefit these 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 six months post-OCU400 dosing by assessing improvement in the best corrected visual acuity, that is BCVA, at four or more letters and seven or more letters from the baseline. We also looked at improvement in low luminance visual acuity score at equal or more than five letters and equal or more than 10 letters from the baseline. We also looked at the changes in the MLMT test at different lux level, that is equal or more than three lux levels, equal and more than one lux levels of improvement or stabilization, that is no change in the lux level, demonstrating stability.
Lot of subjects in these trials also shows the ceiling effect, which can be defined when a subject passes MLMT test at the highest lux level, that is at the lowest limit of luminescence intensity, which was one lux in this trial 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 ±3 letter change for BCVA and LLVA, is considered as a stabilization and the zero lux level change for MLMT. Or improvement in all 3 parameter for BCVA and LLVA was defined as any change which is four or more letters, improvement, and for MLMT, 1 lux level or more, were considered as improvement to demonstrate the efficacy of OCU400. Non-responder for each parameter set are shown outside the circle for each group. Overall responder analysis for all these three efficacy endpoints is presented here in bar graph, that is BCVA, LLVA, and MLMT. Results 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 four or more letters of improvement, whereas 33% subjects showed seven or more letters of improvement in BCVA scores from baseline. When you look at the LLVA, that is middle panel, 42% of subjects showed five or more letters improvement, whereas 25% subjects showed 10 or more letters of improvement in LLVA score from baseline. In MLMT, 33% of subjects showed one or more lux levels improvement, whereas 17% subjects showed three or more lux levels of improvement from the baseline. So in summary, overall, OCU400 demonstrated a favorable safety and tolerability profile. Our clinical study suggests positive trends in BCVA, MLMT, and LLVA scores. The key efficacy outcome from the 12 subjects demonstrated four 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 nine out of 12, demonstrated a stabilization or improvement in treated eyes in MLMT score from baseline. In RHO mutation, specifically, 86% subjects, six out of seven, experienced either stabilization or increase in MLMT score from baseline, among which 29% subject demonstrated three lux luminance level improvement. This effect in the RHO patients supports the gene agnostic mechanism action of OCU400. As you all know, OCU400 product is the NR2E3-based nuclear hormone receptor modifier gene, whereas the RHO mutation is the unrelated gene.
So the key takeaways from this study is that the clinical study data results 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, and MLMT signal in the study participants. We would like to thank the study investigators, the 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 one-time curative 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 in 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 means 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 somewhat genetically agnostic. That's sort of not for one particular genotype. So I do think that there is potential here for further studying regarding gene modulation.
Thank you, Dr. Lam. Dr. Lejla, what are your final thoughts regarding safety and efficacy of the study?
Yeah, thank you. It's a pleasure to join you all this morning, and super excited about these preliminary results. As a retina surgeon 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 space, 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 key question of safety. I think the results show that this product is safe and, in addition to safety, we actually see excellent 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 a 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 icing on the cake with this trial that really is designed for safety. So truly excited.
T hank you, Dr. Lejla. Now we'll open the webcast for questions.
At this time, I would like to remind everyone, in order to ask a question, press Star, then the number one on your telephone keypad. Your first question today comes from the line of Jennifer Kim from Cantor Fitzgerald. Your line is open.
Hey, good morning. Thanks for taking my questions. Maybe two 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 RHO mutations, or what's the strategy there? And then my second question is, in those patients that maybe have not yet reached six months on trial, could we see updated data in those patients? And have you seen any responses in those patients as well? Thanks.
Great. Thanks, Jennifer. Yes, so our plan is to not only include RHO but multiple mutation, okay, based on this study. And, regarding, like, you know, study update for remaining subject, still we have to, you know, wait for the data. Yeah, minimum six months. Yeah.
Okay. And when could we get that data?
Depending on, like, you know, when we complete the—they complete the 6-month visit, and we complete the, you know, data log. So it may take some time, but I would say probably like, you know, early next year. But in between, like, we'll continue to monitor, you know, as we collect the data. Okay?
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 tests, what do you consider clinically meaningful? Because I know Luxturna, they were looking at a median of at least two lines 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, you know, I consider anything that's above the repeat variability of the test is meaningful to me. So, in terms of visual acuity, certainly five, well, five or six lines is very meaningful. I know that the FDA is a lot more conservative, and they, you know, for the pivotal trials, they often like three lines. But that's probably not going to be reached by many, very many trials. And I think, you know, we're sort of working with the FDA to moderate their requirements.
Okay. And then, do you have any thoughts on the other?
Could you-
On the other question, like, yeah, we don't have as much data on the mobility course, but certainly a change in three levels is highly meaningful.
All right. Thanks for taking my question.
Sure.
Your next question comes from the line of Yi Chen from HC Wainwright. Your line is open.
Hello, this is Yi Chen for RK. Can you hear me?
Yes.
Hello, good morning. Congratulations on the positive results. I have a couple of questions. One is, have you measured the contralateral eye, how they respond? Second question is, can you please give us your understanding of the genetic profile of those nine responders? Yes.
Yeah, thanks. So, yes, we did look at the contralateral 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, contralateral eye has been monitored. And yeah, could you repeat your second part of the question?
The second question is the genetic profile of the nine responders.
Yeah. So we looked at it. It is like mixed. It is across, so it is not like mutation-specific, but, and still we need to collect, you know, what you 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 stage, like, you know, some of the sentinel subject, their response, will be minimum compared to the patient who has like, you know, preserved photoreceptor or you can say less degenerated retina, okay? You expect a better efficacy outcome.
Okay. Thanks for taking my questions.
Again, if you would like to ask a question, please press star one on your telephone keypad. 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're excited about the future 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.