Good afternoon, and thanks for joining us to have a conversation with Shankar Musunuri, CEO, and Huma Qamar, CFO—I mean, CMO of Ocugen. Ocugen is a biotech company focused on discovery, development, and commercializing novel gene and cell therapies. The company's proprietary gene therapy platform has generated numerous clinical candidates with potential for three BLA submissions in the next three years, starting in 2026, so the first BLA submission is targeted in 2026 with the lead clinical candidate, OCU400, which is currently in Phase 3 for treatment of retinitis pigmentosa, or RP. The second drug is against Stargardt disease, which is OCU410ST, and then the third one is against geographic atrophy, or GA, which is OCU410. And that is targeted in 2028, so to discuss these three assets and this company strategy itself, I invite Shankar and Huma to this conversation, so glad to see you both.
Thank you.
And thanks for accepting our invitation. So Shankar, just to start off, especially for those folks who are new to Ocugen and how would you help them understand what Ocugen stands for, and especially some of the technology that you folks have developed?
Yeah. First and foremost, we're focused on gene therapies targeting many blindness diseases. The three targets we have: retinitis pigmentosa, Stargardt, and geographic atrophy, which is part of dry age-related macular degeneration. They should cover and encompass the majority of the blindness diseases or vision loss diseases with significant unmet medical needs we have today. So our goal is to, as you stated, our team works very hard. And in fact, we started dosing our first patients in 2022. And today, we're leading ophthalmology gene therapies because of the depth and the breadth of targets we have. And these three therapies, we are planning to have three BLAs in the next three years, and that should have a significant impact on these patients globally.
So Ocugen's mission is to not only take these therapies to the market, as we are planning for the next few years, and also work even harder to provide market access to patients who need them globally.
Then in terms of the platform itself, which is the modifier gene therapy platform, Huma, can you just describe for us a little bit about the technology itself?
Our novel modified gene therapy platform, there are two products. It's OCU400, and there is OCU410 for geographic atrophy and for Stargardt as well. Let me start with OCU400, as our liMeliGhT modified gene therapy trial is up for the BLA next year, 2026, broad RP indication. What it is, is that we have only one approved product. I'll try to give some background so that people are able to understand what we do and what's the relevance of that. Luxturna is the only approved product which has been covering only less than 1% of RPE65 mutation of the entire RP landscape. We are the only, I should say, game in town for broad RP indication. 98%-99% of the patients could have potential therapy in the next year or so.
What does it mean is that we are resetting the homeostasis and improving the outer nuclear layer. What does it mean is if you look at the laptop, you shut it down and you just open it back on, it just resets everything. So for these patients, particularly, it's virtually, like I would say, impossible to have one product for more than 100 mutations that we have at this moment. So our trial, liMeliGhT, is covering not only clinical and/or genetic diagnosis, but all more for syndromic and non-syndromic forms as well. On the other hand, the second novel modified gene therapy that we have is 410, which is a unique four-way mechanism of action. The approved products only cover complement system.
We are covering all four, including not only complement system, oxidative stress, lipid metabolism, and reducing inflammation, which is right from the pathophysiology of the disease.
Fantastic. So let's start with the OCU400 because that's the key program, and it's just coming up to a BLA next year. If you can help us understand the design of the study and also the two patient populations that you're trying to address here.
So our liMeliGhT trial, which is OCU400, is Phase 3, and we have actually 150 patients or subjects that we are going to be recruiting: 75 in the rhodopsin and 75 in the gene-agnostic arm, 50 being active and 25 being control. Our primary endpoint of the study is to look at the baseline change for the lux levels, and we're also looking at the treated as well as the untreated, kind of like the difference between the lux level improvement. The secondary efficacy endpoints we're looking into is low luminance visual acuity, and why we have chosen that is very consistent across all our gene therapy programs. In our Phase 1/2, we have established not only our safety, tolerability, efficacy, but also durability at 24 months.
So when we start thinking about these two patient groups, do you expect the data to look different within the two groups, or is it just so that you can cover all of the RP?
That's a great question, and I'm glad you have asked that. Our RP, OCU400, is for early to advanced cases. If you start looking at from 2017 to 2025, many products have failed till so far, and also there is only one approved product for RPE65. The pathophysiology can be a little bit different in terms of clinical symptoms and also reaching at the age maximum as 40, and their symptoms remain the same, but there is no difference. We actually hope to all those patients with unmet medical need, whether it's rhodopsin, whether it's all gene agnostic, which covers all 95% or more of the mutations, not only nationally, but also globally.
I think going back to the basics of science, what she explained, right? So our genes go after fundamentally cellular homeostasis and resetting it and creating a healthy environment for photoreceptors or retinal cells to survive because they're non-dividing cells. That's the difference between our technology and everything else out there. So because of that, we target the entire disease. You take RP, you target the entire disease. You take Stargardt, you got about 1,200 mutations that can cause the disease from ABCA4. If you take gene editing, you need 1,200 products. So we go after the cellular, resetting the homeostasis at cellular level. I think that's a very powerful concept. And what we are seeing in our clinical trials, again and again, we have four publications in Nature demonstrating how these molecules or modified genes are working.
Now we're replicating those results in human subjects consistently across all three programs.
Since you start talking about the clinical data, can you highlight some of the data that you have seen so far in your prior trials? So that gives confidence that the Phase 3 should be positive.
Are you talking about the 400s?
Yeah.
Of course, 24 months durability, safety, and efficacy has been promising. We have, to date, no serious adverse events related to the investigational product across all our programs, such as inflammation, which is the hallmark of the gene therapy. So that is one aspect. The second is in terms of our LLVA at 24 months. We saw the durability, which is more sensitive and specific marker for visual acuity. And that means you are improving the quality of life of patients. And they're basically, when you go to the optometrist or ophthalmologist, you see the vision chart. And if they're able to gain that with a p-value of 0.05, it's clinically meaningful and statistically significant. So that's what we have seen across multiple mutations and over the period of two years.
If we can spend a couple minutes on your primary endpoint, which is the 52-week change in the Luminance-Dependent Navigation Assessment.
Yes.
So what is this endpoint, and how should we think about that in terms of what sort of a change we should see between a treated patient versus if it is a placebo?
Okay, so we do have a control in this as 50 patients. And what we can see, I'll tell you a little bit about Luminance-Dependent Navigation Assessment is basically a mobility test. And it is derived, basically, if you look at MLMT was the basis of approval for Luxturna as well. But they were not sensitive and specific at that time. So you had zero to six levels, we have zero to nine levels, which means we have uniform correlation between the lux intensity and lux levels. It is more calibrated, sensitive, and specific because the heterogeneity of retinitis pigmentosa is more, and we're covering early to advanced cases. What does it mean is that 52 weeks, within a year from the baseline, we're looking at the improvement across all mutations. And that can be between the treated and the untreated control or the control that we are looking into.
That is what we have made this course very sensitive and specific, and that we anticipate that that would be giving the improvement in those patients. There are two things. We are looking at improvement. We're also looking at the photoreceptors of these patients are present as a part of the inclusion criteria that we have. I hope I answered your question.
Yes, and so, Shankar, as we started off this conversation, it's saying this program is built for a BLA in 2026. How is the progress going with this current study? And then when should we see some top-line data so that you can still file in 2026? And would this dataset be good for filing in Europe as well?
Yeah, two questions. First, 2026, obviously. It's assessor-blinded study, so we cannot look at the data during the clinical trial. Number two, so the data will come out next year, and obviously, the BLA, as soon as the data comes out, there are two critical things you need for BLA. One is the CMC. A lot of gene therapy companies struggle, which are doing really well with the quality of the product, and we're already on target to complete our PPQ runs in support of the BLA this year. So that's a big thing, which will be out of the way, so as soon as the data comes out, the top-line results come out, within a few weeks, we'll file the final section. Under RMAT designation, when you have regenerative medicine advanced therapy with FDA, you are eligible to file rolling submission.
So we can start the submission anytime before the clinical data comes out, get the non-clinical section, CMC sections in. As soon as the clinical comes out, it also gives the agency ahead of time alert, and they can start reviewing, and as soon as the clinical data is dropped, that's where your six-month clock starts, so we can do that next year. The second thing is EMA. EMA agreed with our U.S. design, and they said we don't need any clinical trials in Europe. So with this clinical data we have from this single trial in the U.S., they agree we can file for submission for market authorization in Europe, and so they started already allocating resources. They confirmed it will go through the centralized procedure sometime this year, so they're getting ready for that.
Thanks. And then regarding the second program, which is the OCU410ST, so before we go into the program, what is Stargardt disease? Because some folks probably don't know what it is. And in terms of the study itself, what needs to be completed in terms of not only the study, but also if there's any additional work that needs to be done before you file the BLA?
Good questions. I'll try to make it simpler. Stargardt disease is also a form of inherited retinal disease. It is primarily the disease of the pediatric population because it gets manifested there. Majority of the patients do not get diagnosed because of the genetic component or the clinical piece associated with it. But once they are diagnosed, it's in the advanced stage, which means they cannot differentiate between sharp objects. There's blurriness of vision, and they have no other approved product as of right now globally anywhere that could be the potential answer to either reverse or stabilize whatever they have. What we are doing here is that there are ABCA4 mutations that are responsible, as Shankar has mentioned, greater than 1,200 mutations.
Of course, the variation or the pathophysiology of the disease is the bull's eye lesion or the lesion that we have also used as an endpoint in our Phase 2/3 right now as a reduction. Not only that, their quality of life in terms of functional vision, which is also low luminance visual acuity, gets impacted as well. What does it mean for the patient? They are going to get legally blind very soon, even at the ages of 35 and 40. Our trial and our product, OCU410ST, as I've said, the unique four-way mechanism of action with the ABCA4 model. What we are doing at this point is that we are conducting a Phase 2/3 registration trial that we actually got RMAT from the agency with an adaptive design, unique adaptive design.
The purpose of that adaptive design is to look at the sample size re-estimation towards when we have 16 treated and eight controlled subjects. And that's true control. And that will actually dictate us for further action, such as we can even go for approval ahead of time. This is also shaving off two to three years of the framework regulatory process that is very cumbersome, and it means that the potential hope for the patients globally as well and nationally. In terms of the design, we have 51 patients overall, 34 in the treatment, and 17 in the control. And it is also for early to late stages of Stargardt disease.
Pediatric to adult.
Yes.
Since there is nothing to compare against, in the sense there's no drug or anything else, so what would you deem as a positive when the data comes out, and how should we benchmark it so that people like me can understand whether this is something that can get through the regulators and be meaningful in the market?
The first and foremost thing that everybody asks is how we have conducted our Phase 1. We have not only demonstrated safety and tolerability. No serious adverse events related to the product. No adverse events of special interest. So that's actually pretty good. We established our maximum tolerable dose in that way. Phase 2/3, we have been consistently releasing our data, and particularly for 12 months as well, where it says a reduction of 48% from baseline, which is pretty remarkable for that timeline, which is, and these are, as we have mentioned, early to advanced cases and the pediatric population, three years of age and above. So I think we are hopeful, and the data is trending in the right direction, and we are looking into lesion size reduction, which eventually would be, which is the hallmark of the pathophysiology of the disease.
That's the primary endpoint. If you show statistical superiority, the degeneration or the lesion growth, you're slowing it down compared to control untreated or not. I think, as she stated, we have very promising data in Phase 1 if you replicate it and if you show the statistical superiority to control group. Then the secondary endpoint, visual acuity, we're also monitoring.
So I forgot to add one thing. Thank you, Shankar. A single subretinal injection, one-and-done treatment. That's what it is.
Yeah. So in terms of the GA, the third indication, obviously, there are a couple of approved drugs out there. So when you start comparing OCU410 for this indication, how should we think about the data that would come out at the end of Phase 3 versus what people have seen with the true approved drugs?
That's a great question. So first of all, I'll talk about safety. It seems like it is given, but for geographic atrophy, as this is a disease population, we are looking at 50 years of age and above, right? And they with comorbid conditions like diabetes, cardiovascular, all of the above. Safety in the approved products, there were cases of CNV, endophthalmitis, and if you look at the package insert, that was a big talk of the town. We have not reported any serious adverse event related to the investigational product, which is OCU410 and adverse events of special interest. So that is the first hallmark we are looking in as the first comparator. Second is the, from the efficacy perspective, of course, structural growth reduction was something that they looked into, which was not really statistically significant or clinically meaningful, but there was unmet need there.
That's what it was. What we have been consistently looking in our Phase 1 is, and Phase 2, we have released the data at six months for 27% reduction from the baseline, which means there's a true control, high dose and medium dose and a control, which means there is one into one into one randomization, and that, along with Phase 1 data, consistently showing improvement in the LLVA. LLVA is something that also is a hallmark of this OCU410 GA program. There is no approved product in GA, and they are looking into the functional parameters. We are covering it at all fronts. We are looking at structural. We are also looking at functional. I think this would be an amalgamation of both. We have not come up to an agreement as of right now. The data from Phase two will dictate that.
But I think we know that we are going to address structural as well as.
And functional.
Functional. Yeah.
So I think, yeah, that's it. So the two products have structural.
Yeah.
And then safety. And we have structural as well as functional. And it's one and done instead of every month or every other month.
Correct. In terms of the data, at least from the Phase 1 study, I believe we have seen up to six months at this point, so what additional data could we see from that study, especially for the GA product?
Phase 1, we have 12 months. It's actually six months for Phase two. That's what we are going to continuously talk about. We'll consistently talk about. Safety has already been established, but efficacy parameters such as lesion growth reduction and LLVA as well. If you look at that, this is one of the key questions I have been asked, that what's the comparator? If you look at the pegcetacoplan studies and OAKS and DERBY trials, there is even at 24 months, there is only reduction of 16%-18% versus the preservation of retinal tissue that we have seen 27%. We also have seen 0.31 versus what they had even without at three months or six months, we were way above the curve.
If you look at the 27% at six months is more as compared to 24% that pegcetacoplan had at six and 18 months. I think we are trending in the right direction, and this is clinically meaningful and statistically significant.
We're also going to, because the functional endpoint, typically the structural, you'll start seeing the effect with gene therapies sooner. Functionally, it takes time. I think by nine to 12 months, just like we saw in Phase 1 study, by the time we get the 12-month data and the first quarter next year, that should also show, as she stated, LLVA trends. And if they continue like we are seeing in Phase 1, I think that'll give us a very good indication getting into Phase 3. I mean, with gene therapies, the data we released in about 25 patients after six months is remarkable.
So I know we are running out of time, but it'll be remiss if we don't talk about your divestment, right, of the NeoCart asset. So in general, what's your commentary on the divestment itself and how should it help your balance sheet?
Absolutely. Yeah. Currently, we have, I mean, obviously, our focus for the last few years is gene therapies. I mean, that's why, as I stated, 2022, started dosing first patient. Today, we have three programs covering the breadth of many blindness diseases. So we really want to focus on gene therapies and become a global leader. Therefore, the amazing technology we have on cell therapy side for cartilage repairs, articular cartilage defects, and many more technologies we developed, and we got an RMAT designation, and it's a we change the design, put it in a best place for success. And so we're not doing justice to the patients. There's so much of unmet medical need in the orthopedic space. Regenerative medicine is just about to start. So we felt it's better we spin it off. And so they have a focus team really taking it to the patients.
From our balance sheet perspective, overnight, I don't think market really is not deeply looking at it. We created, it's public information, more than $100 million value for NeoCart and our orthopedic regenerative cell therapy assets. We priced it. A combined company will be valued at $150 million with a reverse merger with Carisma. That means they got a $15 million valuation. In parallel to that, we're raising money. So the Ocugen with investors, they'll hold majority of the stake. Ocugen will be a significant component of that. And so that means we'll continue to support them as they need. And as they move forward with their Phase 3 clinical trial, their market comparables are there. There is one regenerative cell therapy company. They're almost trading at 8 to 10 multiples of their revenues. So it's just a matter of time.
What it means, Ocugen has a significant stake, and that means our shareholder value will grow. It's like think like an investment in an asset. If that asset value grows, that'll add it to our balance sheet. We can anytime monetize that too. So that's all going to help with Ocugen to put more resources into our gene therapies. So we hit those three BLAs in the next three years.
So as a last question, what's the strength of your balance sheet at this point in terms of cash, and what sort of a runway could you get?
Yep. I mean, Ocugen, we're very efficiently run if you compare to a lot of biotechs out there in our space. So we have about $12 million a quarter or $50 million. That's our runway with three programs. So based on that, recently, we got a $20 million injection into our balance sheet from a very large fund. And so they also have a very creative way of potentially another $30 million option when the price hits certain target. And so with the $30, we should extend our runway into 2027.
Okay. Perfect. Thank you. Thanks for your time, and good luck.
Thank you for having us.
Thank you for having me.