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 Investor and Analyst Event. [Operator Instructions] Please note that today's conference call is being recorded. Thank you. Tiffany Hamilton, Head of Communications, you may begin your conference call.

Thank you so much, Rob. Earlier this morning, we issued a press release announcing positive preliminary 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 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, proposed, 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 and 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. Now 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 I/II 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 modified gene therapy approach. This is the first clinical validation of the platform with 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 and 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; 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 preliminary Phase I/II trial results. Arun?

Thank you, Shankar. Good morning, everyone. Let's just 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 7 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 1.66x10^10 vg/ml in Cohort 1, or a medium dose, that is 3.33x10^10 vg/ml of OCU400 in Cohort 2, respectively. In the preliminary data analysis, 9-month follow-up data for 3 subjects in Cohort 1 and 6 months follow-up data for 1 subject from Cohort 1 and 3 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 test has been used for the product approval by agency in this [indiscernible] space. The key efficacy outcomes from 7 subjects demonstrated 4 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. And the fourth one, 3 of the 7, that is 43%, of OCU400-treated eyes demonstrated 8-11 letter of improvement in BCVA score compared to none of the untreated eyes. The early results from the patients treated in the Phase I/II 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 III trials in the U.S. and 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 I/II trials for both programs. With OCU410 and OCU410ST, we believe we have a potential onetime 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 I/II trial in your clinic. Dr. Birch?

And I'm happy to report on behalf of our patients. I must say that they are extremely motivated and we've had absolutely no lost to follow-up or missed visits. Patients have been extremely excited to be in this trial and 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 and improved visibility of objects in the treated eye. And these patients, above all, are motivated to retain the vision they have. So we've got a signal in the right direction of improvement that's even better. So it'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.

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

Congrats on the update. 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? And then also, is there a dose response? And would you anticipate, I guess, a dose response related results in the Cohort 3 data? And when can we expect that? And maybe we could start there.

Yes. Thank you, Jennifer. Arun?

Yes. Thanks, Jennifer. So yes, like the MLMT testing we are using is pretty much like a standard -- what is a standard in the field. In terms of like are we seeing the similar trend in terms of delta, what is expected for, like, 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, -- have not evaluated the high-dose cohort data and we are expecting to be that available in coming like next 1 or 2 quarters, but once it is available, definitely we'll be sharing that data with the market. But whatever data we have so far, we are seeing the positive trend in -- towards increasing the MLMT score.

Okay. That's super helpful. Specifically in the BCVA score, just 3 patients, was that in the -- or how is that split between like the cohorts?

So in this analysis, we used total of 7 subjects. And out of those 7, we have 4 subjects in Cohort 1 and 3 subjects in Cohort 2. And those 4 subjects in Cohort 1, they received the lower dose and in the Cohort 2 subjects received the medium dose. But 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. And then maybe 1 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?

Yes. Thank you for the question. Yes, it's exciting to me that one of the groups that we're 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. And so at this point, we have really nothing to offer patients with autosomal dominant retinitis pigmentosa. So 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. And then 1 more question, sorry. I missed some of the slides. The subfoveal detachment, can you give any color around that? Was that just because like at baseline this is a very severe patient, or at any context there?

Let me -- we didn't enroll all the patients. So let me ask Arun to answer that one.

Yes. So Jennifer, this is primarily related to the subretinal dosing procedure. So during subretinal surgery, there can be some instances where fovea get detached when you dose or when you create a bleb and then in follow-up visit it does reattach as well, okay? So this is something common you'll see in the retinal surgery, yes.

Your next question comes from the line of Swayampakula Ramakanth from H.C. Wainright.

A quick question to Dr. Birch. So as you're looking at this data and as we have experienced these patients, what is really meaningful clinically in terms of improvement? 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 things go along? Or can they fall back into the natural history of the disease in the sense the declines could happen again after like a year or 2? What is your thinking based on the data that you're seeing up to this?

So 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, that we get even more improvement over time. There's some trend of that after 6 months, but I really don't want to 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.

So RK, Arun want to add a comment on that.

Yes, RK, I want to add that, one, I think you asked the right question. So as we mentioned in our call, that we have like 3 subjects which we followed up for 9 months. So when we look at those subjects and primarily focus on MLMT scores, we do see a positive trend from, say, 3 months to 6 months to 9 months, okay? And some of those subjects had a meaningful MLMT score change, which is kind of approximately getting a gain of 2 Lux level, that has been kind of basis for some of the product approval. So we are seeing that trend, okay? At 9 months, there are a few subjects, as you can [ see in the Phase II ] also, has improved more than 2 Lux level, and that is meaningful.

And just to follow up on that, so how often is the MLMT test being done on these patients? And according to the protocol, how long are you planning to do this?

So as for the current ongoing study, we plan to follow up all the subjects up to 1 year, but there is extension in this study where we are going to follow up these subjects up to 5 years. And also there is a scope of these subjects receiving investigational drug in contralateral eye if the 1-year efficacy is promising in the treated eye.

Okay. One quick question going back to Dr. Birch. So just because Arun just talked about contralateral, 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. So how distorting is this to the patient? 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. So 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.

It's absolutely ethical to treat the other eye once we have demonstrated some efficacy in the first eye. 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 1 year, and at 1 year we'll be looking at the outcome and making a decision on the other eye. But they're obviously watching each eye separately and they kind of check their vision with the 2 eyes, and 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.

Your next question comes from the line of Uy Ear from Mizuho Securities.

So 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? That's the first question. Yes.

Yes, go ahead.

So in this -- out of the 7 subjects, we have a total of 5 subjects with rhodopsin mutations, and we have 2 subjects with NR2E3 mutations. You did ask how the distribution was across the cohort. So 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. And did you see any differences in terms of improvement, like the one mutation did better than the other, or they were pretty equivalent?

Yes, very good question. Actually, if you look at the distribution, of course, we have more of rhodopsin than NR2E3 subjects. So sample size is not that great to do any power analysis. But if we look at the trend, we are seeing the similar response across these 2 mutations. So we are seeing the improvement in both mutations. It's not mutation specific.

Okay. And did you -- I guess, if you look at the, like, the morphology of the eyes or like do -- did you look at the fundus or the back of the eyes? Anything to see if anything -- an improvement in the structure or -- just curious?

So yes, we -- so the fundus, like, is primarily being used for degenerating, like, geographic atrophy trial. But in this study, like, our primary focus is looking at the improvement in functional vision. And some of the tests we are doing is more related to the functional vision, not directly looking at the structural. But to answer the question, are we collecting structural data as well, yes [indiscernible] where we are doing SDOCT and we'll be looking at some of the structural changes as well in the follow-up analysis.

Okay. And in terms of safety, was there anything that stood out more than others, just curious?

Not till date.

Your next question comes from the line of Robert LeBoyer from Noble Capital Markets.

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. But I'm curious as to what a Lux level actually means to the patient in terms of their ability? And what these measures would mean to a patient in terms of the difference in visual ability and the progression of the disease?

Arun?

Yes. So in terms of like the common practice we see in the field that 2 or more Lux level improvement is considered clinically meaningful. How that translates into like a patient quality of life improvement or vision improvement? So the way we look at the MLMT mobility scores, it's more like ability of a subject to basically navigate through the path with obstacle and mark at the different light levels. So when a subject, say, at the time of a screening performing able to navigate at certain light levels and in the follow-up visit, if that subject is able to navigate with the much lower or dimmer light, that's what you call as a improvement in their mobility score, and that basically translates into the functional region. So 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 region.

I could just add what it means to the patients. I think it extends the range of luminance that they can function under. So one of the huge problems patients with retinitis pigmentosa have is as the light levels decrease, say toward the evening, they -- everything starts becoming sort of invisible and they really can't function at nighttime or in -- even if it's lit up, 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. So I think it's a common thing that we find the improvement sort of the extremes of vision at the end -- at the regions where they are under dim light then we tend to -- it tends to come later to see the improvements at real high light levels. So I think it's encouraging. The other thing, too, is that it's not just nighttime, it's also in dim environments, restaurants or going into rooms that are dimly lit, it takes patients for a long time to adjust to that, and sometimes they never do. So having this kind of improvement in sensitivity is really meaningful to them.

And your next question comes from the line of Jonathan Aschoff from ROTH MKM.

There's a lot of clinical-stage products going after RP. And granted, you're casting a broader mutational net than they are, but how many of those are using MLMT as a primary endpoint?

Arun?

Yes. So most of these -- most of the programs that are in early stage, there are only few who are getting into Phase IIb or so. So if you look at most of these people, especially in IRD space like RP or LCA-related condition, the focus is in the mobility test. And some are -- pretty much like people are using the similar mobility score. They have like slight modification. Some call like Y Mobility Score, some call MLMT. But pretty much everyone, I think, is using MLMT as one of the primary endpoint in their study.

So you would say it's something that's pretty much completely eclipsing [indiscernible]?

Exactly. And it has been used for the approved product as well. Luxturna approval was based on the MLMT score change.

Okay. So is there any difference in the threshold to decide to initiate treatment in the second eye versus the first eye, which at this point in this example is already treated? In other words, commercially, would there be any higher or lower barrier to give the second eye a dose? Or do you envision this question not even being meaningful because you would envision commercially giving both eyes the dose from the start?

Yes. We are planning to go both eyes. Yes.

Okay. So my last is a 2-part question. Two things were asked that I don't think were actually answered. 5 of 7 patients that comprise that 71%, what dose cohort did they come from? And now that you have broke out mutations, what mutation did they have?

So those 5 subjects they come from both Cohort 1 and Cohort 2.

True. But that's 7 patients. So which -- do they encompass all of cohort?

Yes, they do. So we have -- yes, so we have 3 subjects coming from Cohort 1, and 2 subjects is coming from Cohort 2.

Okay. That comprises...

And both the mutation. If I have to define the mutation for those 5 subjects, then we have 3 subjects from rhodopsin and 2 subjects from NR2E3.

Okay. Great. So it incorporates both. And then also I think was asked but lost over was how frequently do you do MLMT?

We do -- like we have a 3-month, 6-month, 9-month, 12-month. And, of course, at the time of the screening baseline.

And 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 modified gene therapy technology, do you have any additional thoughts. Neena?

Thank you. Can everybody hear me?

Yes.

Okay. Great. I think these preliminary results are really exciting and promising. It's, as the inventor, 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 in over 200 paths to get to this disease. And we wanted to develop something that would be valuable and useful for those patients that don't have other options. And so our hope, as Dr. Birch mentioned, that this is unprecedented work that will offer something to those that don't have some hope right now and treatment options. And 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 that Shankar had mentioned. So I really think this is going to revolutionize the gene therapy space for ocular and other diseases.

Thank you, Neena. 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.