Good afternoon, and thanks for joining us to have a conversation with Huma Qamar, CMO of Ocugen. Ocugen Inc. is a biotechnology company focused on discovering, developing, and commercializing novel gene cell therapies and vaccines that improve health and offer hope across the globe. The company's proprietary therapy platform has generated numerous clinical candidates, and as its lead candidate, OCU400, Phase II clinical trials, but going to be Phase III soon. there are Phase I/II studies also with a second candidate, OCU410, for geographic atrophy, secondary to dry AMD and OCU410ST for Stargardt disease. So to discuss company's ocular gene therapy platform, so let's get started with Huma. Glad to see you, Huma, and thank you for accepting our invitation and talk to our audience today.
To get started, can you briefly help us understand what is the long-term strategy of Ocugen in terms of the gene therapy portfolio itself?
Yeah, well, it is my absolute pleasure to be here and to be talking with all the right stakeholders about the company's upcoming product strategy. So, as you are all aware, OCU400 is Phase III. we had successfully completed Phase I/II, and we are moving towards the BLA and approval towards 2026. So that is the key and the prime product that we have. The other two products that we would like to focus on is the OCU410 for Stargardt. That's our human retinoid receptor alpha, orphan receptor alpha, RORA gene, OCU410 for geographic atrophy, secondary to age-related macular degeneration.
We are in the Phase I/II portion of the study, and, we have completed our medium dose cohort for that, and we are moving towards our third cohort towards the next month after the DSMB convenes, this month. What we are trying to do is once we complete Phase II, we are in constant communications with the FDA, Phase III will gonna look like, or what's the path forward, as you are all aware, that it's not an intravitreal product, it's a subretinal injection. For OCU410ST, we have the orphan drug designation, and we are currently in the Phase I/II.
We also have completed our medium dose cohort, and before we move to Phase II, we are going to talk to FDA, and we are currently in conversations with them on what is going to be our strategy in terms of making it to the next level of the registration trial.
So, Ocugen's developed a unique, modified gene therapy platform, and this is quite different from what we know as any other gene-agnostic platforms. Can you help us understand why is it different, and, you know, why did you folks choose this path?
So, this is a great question, and I do get this question till now, even three years have passed, and I would love to answer that in a way that our audience and everybody understands it. So we have proprietary novel modified gene therapy platform. What does it mean is that it's not the regular gene editing or replacement or any other augmentation platform or gene-agnostic platform that we do hear about. Simply, this modified gene therapy platform, I would like to explain it in a way. For example, retinitis pigmentosa is a condition that affects more than 100,000 patients in the U.S., and that is caused by different genetic mutations, and where their phenotype is, you know, is influenced by certain factors.
So what we have, the modified gene therapy platform, we reset the homeostasis. We regulate the photoreceptors and improving the quality of life of patients. What happens here in the novel modified gene therapy platform is that it impacts the phototransduction, it regulates the inflammation or the receptor, photoreceptor survival. For example, you might have a genetic disease which is caused by different mutations, but actually, modified gene therapy platform does not impact the genetic mutation.
It actually impacts the phenotype or overexpression of NR2E3 delivery that we have it in 400, and RORA expression that is for our 410ST and GA that we are utilizing. What our inventor of the program, Dr. Neena Haider, states, and I always like to quote her on these occasions, is that: "One bad apple spoils the bunch." So that's why we are resetting the homeostasis, and basically, it's a one-stop shop to fix the problem.
Correct. So as the OCU400 program goes, it's as you said, it doesn't look at one single mutation; it looks at the family of mutations that end up, you know, showing up as RP or LCA. Just so that our audience understands the two different indications, RP and LCA, how are they related and how are they different? And also, can you highlight some of the data which just come out from Phase I/II program, especially the RP part of it?
Yeah, so in terms of inherited retinal diseases, we classify retinitis pigmentosa and Leber congenital amaurosis. We were conducting Phase I/II study, where we had looked into retinitis pigmentosa, the safety, tolerability, and efficacy portion of OCU400. What we looked into was specific mutations. That's OCU400 related to autosomal dominant rhodopsin, autosomal dominant NR2E3 and recessive NR2E3, and Leber congenital amaurosis due to CEP290 mutation, which is LCA10, which is the most common form. So if you look at the prevalence of RP, it's greater than 100,000 and also greater than 30,000 in terms of LCA. And overall, there is the LCA, the patients are referred to as legally blind because there is still unmet medical need, and we do have different subtypes in that.
In terms of how they are different, if you look at retinitis pigmentosa, there is presence of night vision loss, which eventually goes to peripheral and central vision. And that impacts actually their quality of life. So basically, there is a photoreceptor loss, and that's what we are working through the novel modified gene therapy platform. The second thing is Leber congenital amaurosis. That starts in the infants and the early childhood, and that can lead up to legally blind. And the patients that we actually enrolled in our trial were actually the quite classic depiction of the CEP290 or Leber congenital amaurosis with the signs and symptoms. So they are diagnosed clinically, and secondly, with a genetic diagnosis.
In terms of Phase I/II data, I would like to summarize it meaningfully in a couple of sentences. That study has given us some positive trends. From safety perspective, there was, you know, we had a great safety and tolerability profile. However, from the efficacy perspective, we're glad to see some signals and some positive trends that we have shared periodically with the market. So if you look at rhodopsin patients, 80% of the rhodopsin patients, eight out of 10, showed improvements from the baseline, from the baseline to MLMT. So MLMT is Multi-Luminance Mobility Testing, which was an approved endpoint or a marker for a Spark Therapeutics Luxturna.
In terms of overall mutations that we had, 14 out of 18, 78% of the participants showed improvement from baseline to MLMT, all mutations that were there. And last but not the least, BCVA, LLVA, which is Best Corrected Visual Acuity, Low Luminance Visual Acuity, and MLMT, we did see 89%, almost 16 out of 18 participants showed either the positive trends, stabilization, or improvement in one or the two parameters.
Perfect. So on the LCA portion of the study, I think it's still ongoing, correct? And, so when should we expect that data?
Yes. So it is ongoing. As you know that with any gene therapy, it's six months minimum readout data is required. So we have data coming in, and we are hopeful to present it soon in early next quarter. And we are working to formulate that data and you know, share it with the market as it becomes available.
So as you stated, you know, you Phase III program, especially for the RP/LCA portion of the study. So can we talk a little bit about the design itself Phase III part? and also, you brought in a new endpoint. The LDNA endpoint. So how is that different from MLMT? And also, what's the reason why you need to work on LDNA, not MLMT, that you have already shown positive data on?
Yeah, so that, that's a great question. Phase III perspective, we from OCU400, we are the only company with a broader RP indication, retinitis pigmentosa indication. What does it mean is that we are covering the gene-agnostic portfolio there.
Sure.
So, to make it easy, there are two. It's basically randomized, masked, controlled study, which means that we will have 2:1:1 arm, which means that we will have treatment groups as well as control group as well. So we have one arm with rhodopsin patients, which is 75 patients, 50 in the active, 25 in the control. Same 75, 50 in the active, 25 in the control in the gene-agnostic arm, except the autosomal dominant NR2E3 subjects there and rhodopsin. So what we are looking at is that all comers will go into gene-agnostic, which actually validates our platform, what we are saying.
Since the beginning or the inception of the study or the IND that we have been talking about. So once we have that, we are looking at the primary endpoint, which is from the baseline to 52 weeks through the Luminance-Dependent Navigation Assessment , which is LDNA, 2 lux levels improvement. And when I do get this question a lot, that: How is it different, and is it different from the MLMT, and what you guys are doing, is it altogether different? Well, the basic foundation, I would give an example, simply is that when you have an iPhone 14 and you upgrade it to iPhone 15, you will have the basic infrastructure of that, but there will be some features that will be different.
What we did is that for the MLMT, which is an approved endpoint for Spark Therapeutics, that's the basis, the foundation is the same that we have taken in. The only thing that we have changed is the lux intensity levels and the lux levels in terms of capturing the actual change and improvement, which is 2 lux levels. For example, 0-6 levels were in MLMT, so now 0-10 levels in the LDNA, which is proprietary to Ocugen, and it's called Luminance-Dependent Navigation Assessment , but nothing new or out of the ordinary or out of the blue with the basic thing. However, we have changed the intensity because as we go, there is a lot of heterogeneity in these IRDs. We want to capture a meaningful change.
Obviously, LDNA is going to be more sensitive, if I can use that word-
Yes
compared to what you're doing at the MLMT. So, do you, is that because you're becoming, you're looking at mutations or all mutations, and there may be certain mutations which are more sensitive to a certain part of the lux scale? Is that one of the reasons, too?
That's what I'm mentioning, that there is a heterogeneity. And what we have learned, there are certain learnings from the MLMT that we had in our first trial, that was if you look at Spark Therapeutics and Luxturna, they were only utilizing RPE65 mutation, which makes less than 2% of the mutations accounted for the retinitis pigmentosa. When we talk about the IRDs, and particularly the retinitis pigmentosa and the gene agnostic arm, we have to see everything, and you want to really have a meaningful change. What does it mean in terms of light intensity at lux levels? For example, the patient might be able to see in the bright light, but might not be able to see in the dim light. Now, dim light can be any dim light.
There are different levels or, you know, scales of dim light. It might be moonlight. It would be very dark light. So we have made those changes to capture exactly what our investigational product, which is OCU400, is having an efficacious, you know, effect. So I think that was the reason that we did come up with this. And this was all, by the way, created with the help of FDA. And we had the buy-in and the back-and-forth conversation, so this was not something that we just thought out of the blue, but it was very thoughtful discussion with the FDA.
You also have, as you mentioned, you also have the gene agnostic arm. What's the basis for having that, and how is that going to help in the label?
So the gene agnostic, as I said, that we have a broader RP indication, which means that, you know, everything that comes under that umbrella. We have a lot of heterogeneity. We have patients that present with clinical symptoms, which might be similar, but not as compared to the genetic mutations. For example, rhodopsin, if you see from Phase I/II study, they showed really the improvement, which is 10%-12% that make up the population. And it's very hard. I mean, if you look at the clinical data and the literature review, there is not much to be done for rhodopsin. Same goes for the CEP290 that, you know, we are now looking into that as well.
When we look into the gene agnostic arm, we are really trying to be representative of majority, which is 90% of the population whether they are in U.S. or in European Union. Recently, we got approval or the positive scientific advice from European Union, where they said that if you have U.S. sufficient data, we will be able to like, you know, we don't need another trial in European Union. So in terms of from the label perspective, yes, it would be. I like to use the word one-stop shop. It would be that. But yes, the indication would be for RP, and there is a separate indication for Leber congenital amaurosis. So that is one thing that I would like to mention.
Of course, we are in, you know, something it's like a little premature to you know, mention anything till we get the data, but that would be something that would come after the consultations with the FDA as well.
So based on your conversations with the regulatory authorities, whether it's in the U.S. or in Phase III study is good for approval?
Yes, that's what we got. That's the positive advice we got from EMA, and which was very. I, I think that was a win-win situation for us as well because we do have a broader, you know, RP indication, as well as, we do have RMAT designation, too. So I think that's something that puts us on a little bit different bar, and, we can move forward with a little bit of flexible regulatory strategy.
Perfect. So talking about the LCA portion of that study, so when do you think you can finalize the data from Phase I/II and, you know, get started with an LCA arm on the Phase III?
As I've mentioned, next, early next quarter, we are presenting that, and the next quarter, we will be working with the regulatory agency to provide that data and get their concurrence on how to proceed forward with that. Because the idea of OCU400 is that it is gene agnostic.
Perfect. Then moving on to 410. We know we don't have too much time on it. So, the two indications that you're looking at, the Stargardt disease and the GA secondary to dry AMD. And you started off on the GARDian study and you, you, yeah. So within that study, what's the design first, and then when should we expect some of the data from that?
Yeah, so it's a, it's a classic Phase I, three plus three dose-ranging, dose-escalation study, and we will be enrolling up to 18 subjects. If, if DLTs, dose-limiting toxicity, if no, there will be 9 and overall 42 subjects altogether, Phase I and Phase II. Phase II, we will have the two dose levels, which is the maximum tolerable dose that we will be establishing from Phase I. We are also dosing pediatric population Stargardt.
As I mentioned, that pediatric population, it impacts more in the pediatrics, and there will be a maximum tolerable dose and low dose, and in fact, a control as well. In that case, we are having 12 adults and 12, pediatric population as well. And, that, right now, the medium dose has been completed successfully, and, once we get the DSMB concurrence in June, we will be able to complete the high dose dosing in July. So I think, around that time, we are hoping to get the data as it comes, and, we will be periodically informing the market, but it would be next quarter, of course.
So within the Stargardt disease space, is there anything out there for these patients, or is this gonna be?
There is no approved product. There is only one from another company that is in the clinical development phase, and we have got orphan drug designation. So, what I had mentioned earlier in the conversation was in the Phase I, we will gather that data, work with the regulatory agency, and to look at it with the approval process, if they advise.
So regarding geographic atrophy, so when would you be able to start that study? And, you know, what sort of data do you need to show in that? Because obviously there are therapies which are already approved for that.
So we already have started the ArMaDa trial, which is a GA. We have completed the medium dosing. Our DSMB convening is this month, and we will be finishing, hopefully, our dosing, towards the end of June, beginning of July. Then, we will be able, in the early next quarter, provide you with some updates. Same design, dose escalation, dose ranging, 2 dose levels in phase 2. However, 1:1:1 ratio, which is 15, 15, 15, up to 63 subjects in total.
Okay. And then in terms of the data that's coming out of that trial, what should we be looking for? Because as I said, Apellis has- as a drug out there, so and it looks like they're doing pretty well in the market right now. So how should we differentiate these therapies?
So one thing is that those are intravitreal injections. There is a patient compliance issue that is six to 12 injections per year. However, we are working on the four unique mechanism. They're only targeting the blocking of complement activation or cascade. We are working on oxidative stress and inflammation, and lipid metabolism, or the anti-drusen activity reduction. So I think that is a very unique concept, where we are in the novel modified gene therapy, utilizing the RORA gene. And that would have an impact as a, as, like, a once, one-time gene therapy application.
Perfect. I think with that, we are out of time, but thank you very much for joining me here and talking about Ocugen and discussing your plans.
Thank you for having me here today.
Thank you.
Thank you.