Good morning. My name is Rob. I will be your conference operator today. At this time, I would like to welcome everyone to the Ocugen Investor and Analyst event. 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. Please note that today's conference call is being recorded. Thank you. Tiffany Hamilton, Head of Communications, you may begin your conference now.
Thank you so much, Rob. Earlier this morning, we issued a press release announcing positive preliminary safety and efficacy results from our phase 1/2 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 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, including, but not limited to, statements regarding the development of OCU400 and the interpretation of preliminary clinical trial results.
We may, in some cases, use terms such as predict, believe, potential, propose, continue, estimate, anticipate, expect, plans, intend, 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, uncertainties that may cause actual events or results to differ materially from our current expectations, including but not limited to risks that preliminary clinical data may not be indicative of final clinical data or data in later stage clinical trials. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission. Any forward-looking statements that we may 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'd like to introduce Dr. Shankar Musunuri, Chairman, CEO and Co-founder of Ocugen.
Good morning, everyone. We're excited to share preliminary safety and efficacy results from the phase one/two trial of OCU400, a novel modifier gene therapy product candidate for the treatment of retinitis pigmentosa, or RP, Leber congenital amaurosis, or LCA. Joining me today to provide data 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 the Principal Investigator of the study, and Dr. Neena B. Haider, Fellow of Association for Research in Vision and Ophthalmology and the inventor of the modifier gene therapy platform. Welcome, Dr. Birch and Dr. Haider.
It is gratifying to see these positive 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 that OCU400 has the potential to transform the lives of many patients who are struggling with debilitating blindness diseases. Let me give 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 1 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 multiple genes with 1 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. 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 preliminary phase I/II trial results. Arun?
Thank you, Shankar. Good morning, everyone. Let's start with the OCU400 study protocol. This phase I/II trial is a multicenter, open-label, dose-ranging study. We have enrolled a total of 18 retinitis pigmentosa subjects in this study, with 10 subjects in the dose escalation and 8 subjects in the expansion phase. The age of subjects enrolled to date ranges from 18 to 77 years across rhodopsin and NR2E3 gene mutations. We further expanded this phase I trial to enroll LCA patients with the CEP290 gene mutation and the pediatric patients with NR2E3, rhodopsin, and CEP290 mutations. During today's call, we will be presenting preliminary data related to subjects enrolled in cohort 1, that is low-dose cohort, and cohort 2, that is medium-dose cohort of this clinical trial.
A total of seven subjects with moderate to advanced vision impairment due to RP associated with RHO and NR2E3 gene mutations received unilateral subretinal injection of either a low dose that is 1.66 × 10¹⁰ vg/mL in cohort 1 or a medium dose that is 3.33 × 10¹⁰ vg/mL of OCU400 in cohort 2 respectively. In the preliminary data analysis, nine-month follow-up data for three subjects in cohort 1 and six-month follow-up data for one subject from cohort 1 and three subjects from cohort 2 were assessed. Overall, OCU400 demonstrated a favorable safety and tolerability profile. Regarding efficacy, we looked at multi-luminance mobility test, or MLMT, and best corrected visual acuity, or BCVA.
MLMT has been used for product approval by the agency in this disease space . The key efficacy outcomes from seven subjects demonstrated four key points. The first one is 100% of treated eyes showed a stable or improved MLMT score trend. 5 out of 7, that is 71% OCU400 treated eyes demonstrated 1 or more than 1 lux improvement in MLMT score compared to 29% of untreated eyes. 67%, that is 2 out of 3 subjects of OCU400 treated eyes in cohort 1 with 9-month follow-up demonstrated 2 or more lux level improvement in MLMT score compared to none of the untreated eyes. The fourth one, 3 of the 7, that is 43% OCU400 treated eyes demonstrated 8 to 11 letters of improvement in BCVA score compared to none of the untreated eyes.
The early results from the patients treated in the phase 1/2 clinical trial are encouraging and support the paradigm-changing potential of modifier gene therapy technology to address unmet medical needs for patients with RP and LCA diseases. With this favorable safety profile and positive trend in efficacy signals, we are very eager to see longer term data and to potentially initiate phase 3 trials in the U.S. and the EU. Now I will hand it over to Shankar. Thank you.
Thanks, Arun. As I had mentioned at the beginning of the call, the next gene therapies we intend to bring into the clinic are OCU410 GA dry AMD and OCU410ST . We are on track to submit INDs to the FDA this quarter to initiate phase 1/2 trials for both programs. With OCU410 and OCU410ST , we believe we have a potential one-time curative therapy with a single injection. We're 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. Birch, please share your perspective from the phase 1/2 trial in your clinic. Dr. Birch?
I'm happy to report on behalf of our patients . I must say that they are extremely motivated, and we've had absolutely no loss to follow-up or missed visits. Patients have been extremely excited to be in this trial. The efficacy data that you're showing kind of fits with the kind of reports we're getting back from the patients. They generally feel that there's a sort of a heightened contrast, an improved visibility of objects in their treated eye. You know, these patients, above all, are motivated to retain the vision they have. You know, we've got a signal in this instance, in the right direction of improvement. That's even better. That's kind of a bonus to the patients.
Anyway, I think, we're happy to be in the trial and happy to continue looking forward to some longer-term results.
Thank you, Dr. Birch. Now I'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 comes from a line of Jennifer Kim from Cantor Fitzgerald. Your line is open.
Hey, guys. Congrats on the update, and thanks for taking my question. I have a few here. The first one, on the testing of the lux level, is there a way you can frame that for us in the context of what we've seen with, I guess, approved gene therapies in eye diseases like Luxturna? Also, is there a dose response, and would you anticipate, I guess, a dose response-related results in the cohort 3 data? When can we expect that? Maybe we could start there. Thanks.
Yeah. Thank you, Jennifer. Arun?
Yeah. Thanks, Jennifer. Yes, like, you know, the MLMT testing we are using is pretty much like a standard, what is a standard in the field. In terms of like, you know, are we seeing the similar trend in terms of data, what is expected for like, you know, to define the clinically meaningful change, yes, we are trending towards that. That's what our data suggestive of. Regarding like dose response, we are still like, you know, have not evaluated the high dose cohort data, and we are expecting to be that available in coming like next 1 or 2 quarters. Once it is available, definitely we'll be sharing that data with the market.
Whatever data we have so far, we are seeing the positive trend in towards increasing the MLMT score.
That's super helpful. Specifically in the BCVA scores, the 3 patients, how is that split between, like, the cohorts?
In this analysis, we used total of 7 subjects. Out of those 7, we have 4 subjects in cohort 1 and 3 subjects in cohort 2. Those 4 subjects in cohort 1, they received the lower dose, and in the cohort 2, subject received the medium dose. For analysis, we had 9-month data coming from the 3 subjects in cohort 1, and 6-month follow-up data for 4 subjects, of which 1 is coming from cohort 1 and 3 is coming from cohort 2, that is medium dose. I hope that is helpful.
Okay, great. Then maybe one question for Dr. Birch. I know you talked about, I guess, the enthusiasm in the patients in your trial. Where would you see this type of treatment belonging for, I guess, RP patients, and I guess what would the role of this type of therapy play? Thanks.
Thank you for the question. It's exciting to me that one of the groups that we're involving recruiting is autosomal dominant, because as you probably know, the gene replacement therapy kind of approach, LUXTURNA kind of approach, is not appropriate for dominant disease. At this point, we have really nothing to offer patients with autosomal dominant retinitis pigmentosa. Having a treatment that works across multiple genes, and especially across dominant genes, I think is exciting and there's really nothing else quite like it.
Okay. One more question. Sorry.
Sure.
I missed this on one of the slides. The subfoveal detachment, can you give any color around that? Was that just because, like, at baseline, this is very severe patient or any context guide?
We didn't enroll all the patients. Let me ask Arun to answer that one.
Yeah. Jennifer, this is primarily related to the subretinal dosing procedure. During subretinal surgery, there can be some instances where, you know, fovea get detached when you dose or when you create a bleb, in follow visit, it does reattach as well. Okay?
Oh.
This is something common you see in the retinal surgery. Yeah.
Okay. Awesome. Thanks for taking all my questions, guys, and congrats again.
Mm-hmm.
Thank you.
Your next question comes from the line of Swayampakula Ramakanth from H.C. Wainwright. Your line is open.
Thank you. Thanks for doing this, Shankar and Arun. A quick question to Dr. Birch. As you're looking at this data and as you have experienced these patients, what is really meaningful, you know, clinically in terms of improvement? You know, and what is your thinking regarding as you continue to follow up with these patients, would the improvement, would the change in the mobility test improve as it things go along or, you know, can they fall back into the natural history of the disease in the sense, the declines could happen again after like a year or two? What is your thinking based on the data that you're seeing up to this point?
I think it's just too early to really tell. I would hope that we would continue to see sort of a divergence between the treated eye and the untreated eye, you know, that we get even more improvement over time. There's some trend of that after six months. I really, you know, don't wanna speculate on how long this benefit would last. I mean, certainly with other gene therapies, we've had really long-term success, but can't really say.
Thank you.
Yeah.
RK, Arun wanted to add a comment.
Yeah, RK, I want to add that one. I think you asked the right question. As we mentioned in our call that we have, like, you know, 3 subjects which we followed up for 9 months. When we look at those subjects and and primarily focus on MLMT score, we do see a positive trend from, say, 3 months to 6 months to 9 months . Okay? Some of those subjects has a meaningful MLMT score change, which is kind of, you know, approximately getting, you know, gain of 2 lux levels . That has been kind of basis for some of the product approval. We are seeing that trend, okay? At 9 months, there are a few subjects, as you can see from the base results, has improved more than 2 lux levels , and that is meaningful.
Just to follow up on that, how often is the MLMT test being done on these patients? According to the protocol, how long are you planning to do this?
As for the current ongoing study, we plan to follow up all the subjects up to one year, but there is extension in this study where we are going to follow the subjects up to five years . Also, there's a scope of, you know, these subjects receiving investigational drug in contralateral eye if the one-year efficacy is promising in the treated eye.
Okay. One quick question going back to Dr. Birch. Just because Arun just talked about contralateral eye, I'm assuming what that means in plain English is one eye you treat and the other eye you're not treating in the same patient. How distorting is this to the patient? You know, if this is really working, one eye gets improving better, day by day, and the other eye is kind of, stable or getting worse as the disease progresses. Does it, like, really distort the patient, and at some point it's, ethically, reasonable for us to go back and treat the other eye as well?
Actually it's absolutely ethical to treat the other eye once we have demonstrated some efficacy in the first eye. You know, these patients are just so thankful to be involved in the trial at all. They don't really question the protocol. They know that it's one year, at one year we'll be looking at the outcome and making a decision on the other eye. You know, they're obviously watching each eye separately, and they kinda check their vision with the two eyes. They're aware that they're seeing some increased contrast in the treated eye.
Fantastic. Congratulations. Thank you, very much, Shankar, for doing this. I think this is, we are getting into some really interesting area.
Thank you.
Good.
Your next question comes from a line Uy Ear from Mizuho Securities. Your line is open.
Good morning, guys. Thanks for doing the call. I have a couple of quick questions. Could you elaborate on, like, the number of patients that have the different kinds of mutations, either RHO or NR2E3 gene mutations? Just curious, like for each of the cohorts, did all the patients have different mutations or all the patients have the same mutations? First, that's the first question.
Yeah.
Yeah.
Thanks. Yeah.
Go ahead.
In this, out of these 7 subjects, we have total of 5 subjects with rhodopsin mutation, and we have 2 subjects with NR2E3 mutations. You did ask how the distribution was across the cohort. In cohort 1, we have enrolled a total of 4 subjects, and they all were rhodopsin mutation. In cohort 2, we have 2 subjects with NR2E3 mutation and 1 subject with rhodopsin mutation.
Okay. Did you see any differences in terms of improvement? Like, did one mutations did better than the other, or they were pretty equivalent?
Yes, a very good question. Actually, if you look at the distribution, of course we have more of rhodopsin than NR2E3 subjects. Sample size is not that great to do any power analysis. If we look at the trend, we are seeing the similar response across these two mutations. We are seeing the improvement in both mutations. It's not mutation specific.
Okay. I guess, did you look at the like the morphology of the eyes or, you know, like do a, you know, did you look at the fundus or the back of the eyes or anything to see if anything's an improvement in the structure or? Just curious.
Fundus imaging is not the primary endpoint used in degenerative geographic atrophy trials .
Mm-hmm.
In this study, like our primary focus is looking at the improvement in functional vision. Some of the tests we are doing is more related to the functional vision, not directly looking at the structure. To answer your question, are we collecting structural data as well? Yes, we have done it, where we are doing SD-OCT, and we'll be looking at some of the structural changes as well, in the follow-up analysis.
Okay. In terms of safety, was there anything that stood out more than others? Just curious.
Not till date.
Okay. All right. Thank you.
Thank you.
Your next question comes from the line of Robert LeBoyer from Noble Capital Markets. Your line is open.
Good morning, and congratulations on this data. This looks like you've met some nice clinical measures, and the treatment seems to be working. I had a question more on the practical abilities and functions that the patients see. There was just a brief mention of that a little earlier. I'm curious as to what a lux level actually means to the patient in terms of their ability and, you know, what these measures would mean, you know, to a patient in terms of the difference in visual ability and the progression of the disease. Thanks.
So, um-
Arun?
Thanks, Shankar . Yes. In terms of the common practice we see in the field that a 2 or more lux level improvement is considered clinically meaningful. How that translates into a patient quality of life improvement or vision improvement? The way we look at the MLMT mobility course, it's more like ability of a subject to basically navigate through the path with obstacle and mark at the different light levels. When the subject, say, at the time of a screening, performing, able to navigate at certain light levels, in the follow-up visit, if that subject is able to navigate with a much lower or a dimmer light, that's what you call as an improvement in their mobility course.
That basically translates into the functional vision. In summary, in the field, we consider 2 or more than 2 lux level improvement as a clinically meaningful improvement, and that adds value to the patient vision.
I could just add Yeah, just add what it means to the patients. I think it extends the range of luminances that they can function under. One of the huge problems patients with retinitis pigmentosa have is as the light levels decrease, say, toward the evening, everything starts becoming sort of invisible, you know. They, they really can't function at nighttime or in... even if it's, if it's lit up, you know, they have a real problem. If you're extending the range that they can function under by 2 lux, that means that they're able to do much more with their lives under those conditions. I think, you know, it's a common thing that we find the improvements sort of at the extremes of vision.
At the end, at the regions where they're under dim light, it tends to come later the, to see the improvements under real high light levels. I think it's encouraging. The other thing too is that it's not just nighttime, it's also in dim environments. Restaurants, going into rooms that are dimly lit. It takes patients a long time to adjust to that, and sometimes they never do. Having this kind of improvement in sensitivity is really meaningful to them.
Great. Thank you very much for that.
Yeah.
Your next question comes from the line of Jonathan Aschoff from Roth MKM. Your line is open.
Thank you, guys. You know, there's a lot of clinical stage products going after RP, and granted, you're casting a broader mutational net than they are. How many of those are using MLMT as a primary endpoint?
Arun?
Yeah. So, most of these, you know that most of the programs, they're in early stage. There are only few who are, you know, getting into phase 2B or so. So if you look at most of these people, especially in IRD space like RP or LCA-related mutations , the focus is in the mobility test, you know. And some are, you know, pretty much like, you know, people are using the similar mobility course. They have like, you know, slight modification. Some call like, you know, Y mobility course, some call MLMT. But pretty much everyone, I think, is using MLMT as one of the, you know, primary endpoint in their study.
You would say it's something that's, you know, pretty much completely eclipsing BCVA?
Yeah. Exactly. It has been used for the approved product as well. LUXTURNA approval was based on the MLMT score change.
Okay. Is there any difference in the threshold to decide to initiate treatment in the second eye, you know, versus the first eye, which at this point in this example is already treated? You know, in other words, commercially, would there be any higher or lower barrier to give the second eye a dose? Do you envision this question not even being meaningful because you envision commercially giving both eyes the dose from the start?
Yeah, we are planning to go both eyes. Yes. Yep.
My last is a two-part question. Two things were asked that I don't think were actually answered. Five of seven patients that comprise that 71%, what dose cohort did they come from? Now that you broke out the mutations, what mutations did they have?
Those 5 subjects, they come from both cohort 1 and cohort 2.
True, but that's 7 patients. w-which.
Yes.
Would they encompass all of cohort?
Yeah, they do. We have three subjects coming from cohort one and two subjects is coming from cohort two.
Okay. That comprises the five.
Both the mutation. If I have to define the mutation for those five subjects, then we have three subjects from rhodopsin and two subjects from NR2E3.
Okay, great. It incorporates both. Then also, I think what was asked but glossed over was, how frequently do you do MLMT?
We do like, you know, we have a 3-month, 6-month, 9-month, 12-month.
Okay, thank you very much.
Of course, at the time of screening, baseline.
Definitely.
There are no further questions at this time. I'll turn it back over to Shankar for some closing remarks.
Great. Thank you. Before we close, I'd like to ask Dr. Haider, as the inventor of modifier gene therapy technology, do you have any additional thoughts?
Thank you.
Nina?
Can everybody hear me?
Yes.
Okay, great. I think these preliminary results are really exciting and promising. As the inventor, it's gratifying beyond measure to hear these initial outcomes and the patient stories. The modifier gene therapy platform came from our understanding of the complexities of how genes are interacting, and over 200 paths to get to this disease. We wanted to develop something that would be valuable and useful for those patients that don't have other options. Our hope, as Dr. David Birch mentioned, that, you know, this is unprecedented work that will offer something to those that don't have some hope right now and treatment options. These studies also support the validity of using this modifier gene therapy platform to treat conditions that are caused by multiple genetic factors, such as dry AMD, as Shankar Musunuri had mentioned.
I really think this is, you know, gonna revolutionize the gene therapy space for ocular and other diseases.
Thank you, Nina. Thank you, Nina. Thank you all for joining us this morning. We're excited about what the future has in store for Ocugen and the patients we aim to treat. Have a great weekend. Thank you.
This concludes today's conference call. Thank you for your participation. You may now disconnect.