Conference Transcript - OCGN 2026-06-04

Annabelle Ayer, Analyst — Barclays

Hi, good morning, everyone, and welcome to the Ocugen session. Ocugen is in the gene therapy world, not for systemic diseases, but for retinal diseases, which is very localized and gives the company a very different risk profile. We're happy to have CEO Shankar Musunuri here with us today, who will go through the late stage pipeline. As you know, gene therapy for inherited retinal diseases were among the first to be approved. So there's a lot of strong history and understanding there. So Shankar, let me give you the floor and you can cover the story briefly and then we'll launch into Q&A. Great. Thank you,

Shankar Musunuri, Chairman

Annabelle. Thank you for having me today. I mean, you'll see it on this slide. We're really trying to bring this cutting edge technology to the market and also work harder to provide market access for patients who need them globally. Significant unmet medical need. When you look into vision loss diseases across the board, we are working on majority of those diseases which exist today with significant unmet medical needs, starting with dry agulated macular degeneration, the late stage of it is called geographic atrophy. About 10% of very MD patients have GA. That means they have central vision blurriness when you're 60 or 65, and it's a very debilitating disease. Currently, there are two approved products in the U.S. There's nothing across the board. And we are planning to get into phase three shortly with that program, with the global trial, so that we have hope for these patients. It's two to three million patients in U.S. and E.U. together. The second program, retinitis pigmentosa, is a big inherited retinal disease. Defects in over 100 genes can cause it. And there's a first product, as Annabelle stated, Luxonugget ever approved 2017. It covers only one out of those 100 plus genes. And so taking a traditional gene therapy, you need 100 plus products. However, with our gene therapy, we're able to encompass all these patients with one product. So that's 300,000 patients in USMDU alone. The next one, Stargardt disease, there's nothing for these patients globally. And we are trying to address 100,000 patients in USMDU. All these diseases are debilitating. that eventually most of these patients do become legally blind. And what we are trying to do is bring first-in-class gene therapies for these patients, potentially with one-time treatments for life. I mean, triggering a massive, you know, we're going after massive diseases. Unlike traditional gene therapies targeting 200 or 2,000 patients, we're going after hundreds of thousands to millions. So in this one, there is a direct comparison of conventional gene therapy versus modifiers. I'll target like a few things in there. One of them, if you take it like mutation specific, something like retinitis pigmentosa, defects in over 100 genes can cause it. You need more than 100 products. However, since we use master regulator modifier genes, can target the entire disease with a single product. Therefore, our one product can target that. Also diseases such as geographic atrophy have many complex pathways and our genes can address and regulate all those pathways and also bring healthy environment for cells to survive. Because of that we're able to target complex diseases and diseases which are inherited in nature with a single product. We have many accelerated pathways with our products with FDA as well as EMA. So before I go into our pipeline where we are, I just want to distinguish why our gene therapy is very distinct and different, everything else out there. If you take any standard therapies, typically what you're doing is at the symptom level, you're intervening and you're slowing down disease progression. But if you take the traditional gene therapy, you assume the network is okay, but network is not okay. Genes don't work in isolation. They work as a network. So when I have a defective gene, the defective gene dysfunction causes network to suffer the toxic effects of it. That's why if you give functioning gene for retratational gene therapy, depending on when you give that, it may have different impact outcomes. So what we need to think about genes don't work in isolation. How do you bring the homeostasis the entire network? That's what our genes are able to do So in case of RPS Targard, it's a rare disease and inherited in nature. GA is age-related. In all these cases, our genes have ability to reset the homeostasis, work on the entire network, and also create a healthy environment for retinal cells to survive. And because of that, we're able to target large diseases with a single product. So we have three programs currently, two already in phase three, and one of them is about to get there. OCU-400, targeting retinitis pigmentosa. It's enrollment completed this year. Top-line results are expected in first quarter next year. And because of the RMAT designation, we're eligible for rolling submission. We're going to initiate this year, third quarter. And as soon as the top-line results come in, within a few weeks, we'll drop the clinical module. That will start the six-month accelerated clock for potential approval in late next year. Second program, Stargardt Disease, OCU-14ST. It's going through phase two, three registration trial. We are anticipating interim outcome analysis for any size adjustment in third quarter of this year that will minimize any risk to phase three clinical trial. If everything is on track per plan, we should be able to have top-line results in second quarter and release, then file the BLA right after that. Both retinitis pigment on Stargard programs where alignment with EMA, the single study we're doing in US is good enough to file market authorizations in EU. The last program, RK410, we recently released a very promising phase two data. We are working with EMA and FDA for a global clinical trial with two key endpoints. One, lesion as a primary. Secondary is ellipsoid zone, which correlates to visual function. And we're anticipating alignment by third quarter so we can initiate the phase three. And that will be targeted for BLA approval in 2028. So in a nutshell, we are targeting with our genes, major unmet medical needs today exist globally for three major vision loss diseases, retinitis pigmentosa, Stargardt, geographic atrophy, three BLAs by 2028. That's our target.

Annabelle Ayer, Analyst — Barclays

Got it. So let me just ask a couple questions regarding these programs. So you mentioned you're a modifier. you're using, you're modifying the master regulator pathways. What specific are you, what specifically are you like providing to that environment? Or is it a protein that is being expressed that you're providing? And is it different between 400 and 410? Just give us a sense of what exactly it is that is changing in that microenvironment.

Shankar Musunuri, Chairman

Yeah, yeah. So if you take something like retinitis pigmentosa, we have what we found out irrespective of what genetic defect you have. And whenever you have any genetic defect, you look at the key transcription factors, which are important for key functions in retina, such as cell development, metabolism, inflammation to cell survival. So whenever you have any defect, it could be PDU6B or rhodopsin, we found a link and the key transcription factors responsible for key functions are depressed. And then we found a missing link, that's NRT3, that's also depressed. When you upregulate and all these key transcription factors, they upregulate and reset the homeostasis, and then it creates a healthy environment for cells to survive. And those things I think we modeled in those nature publications looking at pharmacodynamic effects and survival of the cells and the effects. And so today, we see those things in human patients. If you see some of our subjects, not only they're able to slow down the disease progression, some of them, it's stalling the disease progression, stopping it, and some of them, it's reversing it. Similarly, if you take another gene, RORA, which targets Stargardt as well as AMD, Dry Agilate Macular Degeneration, Geographic Atrophy. In both these cases, one of them is inherited disease, another one is age-related, right? And you've got four key pathways which cause degeneration in these patients, oxidative stress, lipid metabolism, inflammation, and complement system. And current therapies for GA target only one pathway complement system. So that's why if you target, if you can regulate all these pathways, and then you can get optimum results. That's exactly RoraGene does. It regulates all these four pathways, and it also resets the homeostasis and also creates healthy environment for retinal cells, photoreceptors, as well as RPA cells to survive. And because of that, we're able to, again, in Sargard patients, and we have data now in some patients up to two years, not only it's slowing down disease progression, some of them, actually it's reversing the disease. They can see better, not just stopping where they are. And I think because of that nature, how our modifier genes are, we call them master regulators work. They work on the entire network and create a healthy environment for retinal cells to survive. Why this is a powerful concept? Because our retinal cells are non-dividing cells. If we can do something to reset them and create a healthy environment, Potentially, we should get the impact rest of your life.

Annabelle Ayer, Analyst — Barclays

Got it. So when you are approaching these diseases, and let's start with RP since it's your latest stage, what stage of disease are you targeting? Is it early stage before they start losing their vision? Have they lost their vision or getting vision restored? can you just help us understand what that ideal patient population is that would better respond to an environment improvement versus the actual gene improvement? Yeah, yeah, absolutely. So if

Shankar Musunuri, Chairman

you take RP patients, if you look at our phase three clinical trial, it's early to advanced stage. I mean, obviously you need to have some photoreceptors there for it to work, right? Because we have to go into directly into retina and inject. And that's where you want the targeted gene expression to get the maximum effect. And so in these patients, as long as you have some vision left, I mean, you cannot give it to people who are legally blind. And you need to have some retina left early to advanced stage and pediatric to adult. It covers and encompasses entire population of RP. And so obviously, I mean, if you go back and look at the data, there are facts. There are many, over 15 companies tried after Luxembourg with the traditional gene therapies to develop therapies. Where are they today? There's only one company doing in phase three. I mean, the traditional gene therapy, it's important. If you give early on, you may have a better effect because they're not really doing anything with the network effect. And so since our genes can, you know, regulate the network, we're able to see benefits patients across from early stage to advanced stage or middle of the disease, all of them are getting benefit. And once again, the benefit may vary where you are and depending on the genetic mutation and type. And I think, I mean, you saw some of the videos on our website there. I mean, one of those patients is actually 60 plus. And so, I mean, obviously he lost most of his peripheral vision. He has central vision left. And now he's getting the peripheral vision back with our therapy. I mean, that's pretty advanced stage, I can call it. and he'd still be able to show the reversal.

Annabelle Ayer, Analyst — Barclays

That was in Stargard?

Shankar Musunuri, Chairman

That's in GA. It's not a retinitis pigmentosa, not GA. Okay, all right.

Annabelle Ayer, Analyst — Barclays

And are all the proteins that you're expressing between 400 and 410, they're not the same. They're targeting different microenvironments, correct?

Shankar Musunuri, Chairman

Yeah, so in 400 with RP, we use NRT3. That's our modifier gene. with the Stargard and GA, we use RORA. That's our modifier gene delivered through AAV vector. Okay, got it.

Annabelle Ayer, Analyst — Barclays

So I guess when there have been so many failures of retinitis pigmentosa, how did the medical community get comfortable with this one? What are some of the findings you had from the earlier studies and what can you share with us today about that?

Shankar Musunuri, Chairman

I mean, once again, some of them, there are two reasons, right? One is a technical reason, and another one is financial. I mean, when you're developing biotech, any novel therapies, I think majority of them had mixed results in early-stage clinical trials, and even some of them had good signals. And at the end of the day, Luxorna was a great technical success. At the end of the day, commercial viability was questionable, just like many gene therapy products in the marketplace. And unfortunately, we're in the field where when you have a novel technology transformative medicine, people expect, you know, significant revenues and commercial success. And so some of these therapies, they struggle, even though they are good, probably promising okay data. At the end of the day, you only have that genetic mutation of 50 or 100 patients. It's very difficult to get capital resources to continue those clinical trials. And so I think majority of those trials, some of them struggled, they failed. Some of them had okay data, they didn't proceed further. And so, only one company right now is in phase three for XLRP. And so, that's the late stage. That covers probably north of 5% of entire RP population.

Annabelle Ayer, Analyst — Barclays

Got it. All right. So, can you, just to give us an idea, are you slowing progression of RP? Are you restoring vision? What should we expect of this upcoming data? What is your actual endpoint? Is it slowing progression or is it actual restoration of vision?

Shankar Musunuri, Chairman

I mean, obviously, what you're looking at is, I mean, whenever you're doing clinical trials for the RP, but using mobility test, which is already approved in the Luxor now, a similar one, obviously, we worked with FDA. We made it more specific and sensitive. We actually validated it in our phase three, which actual patients, very robust. And so here, what you're measuring is you have a treatment group and untreated control group, right? Assessor-Blinder Study. So if you're able to show improvement in the mobility test, which reflects your quality of life improvement, like if I go to a restaurant in a dull light, before therapy, I'm unable to go sit in my chair. I need somebody's help to hold my hand and take me. After therapy, that means I'm performing better in dull light, improving my quality of life. now I can do it myself in a restaurant, dull light setting, I can go sit in my chair. That's an improvement. So this mobility test actually simulates from bright light to dull moonlight. And so our goal is to show the improvement after the treatment compared to untreated control group. I mean, that's a quantitative measure. And in case of other therapies like Stargard and GA, I mean, you have central vision lesions or blurryness. So what you're trying to do is you're trying to compare the growth of that lesion between treatment and untreated group. So if you're slowing it down compared to untreated group, you're measuring it, and statistical superiority based on the design, that means you've got a successful outcome. It's benefiting patients. So in all these cases, obviously, as I mentioned before, you don't need, you know, to show reversal of the disease to get drugs approved. Because many of the drugs in the market today, if you look at it, the majority of them, very close to probably more than 90%. And they're all like slowing down disease progression compared to control arm. But in our case, you know, if the patients are able to stall the disease, that's gold. If they're able to reverse in some cases I mentioned, I mean, that's like a monumental. and it's really, truly transformative. So obviously in the clinical trial, we try to minimize risk as arcogen. You take endpoints which are already approved by FDA because that has a probability of success is high and low risk clinical trial design perspective and you can modify them as needed, but it's good to always take the precedence, right? Then you don't have to prove this endpoint works. And so that's what we are doing for all our clinical. We take something which already approved and then implementing what else is needed around it.

Annabelle Ayer, Analyst — Barclays

Great, great. So I guess, you know, as you might have mentioned, there are several RP gene therapies that are in development right now. You could potentially be the first to market as a gene agnostic approach. Does this put you in a position to be standard of care? and how intense is demand and how important is it to be first? What is your ideal patient here? Obviously, since you're gene agnostic, you could potentially affect everyone. So how do you think about your product versus some other approaches that are being

Shankar Musunuri, Chairman

developed right now? I mean, the only one which is in phase three is XLRP from another biotech company. And obviously, in our clinical trial, if you look at it, we had more than 25 genetic mutations covered. We covered all the major prevalence mutations, which are like, if you think something has three or 4% of RP, like XLRP, rhodopsin, PD-6B, USERS, we covered major mutations. I mean, obviously, we, I mean, our goal is to get a broad RP indication. And sometimes, you know, Some of the patients, it's very difficult to genotype them. If clinically, if they're phenotyped, they have RP, they can be used. I mean, we have expanded access program, very rare. We did it because of empathy for our patients, and they don't want to wait. Either they don't qualify for the clinical trial, or they don't want to wait for two years the product come out. We opened it up, and several patients got expanded access. That's very broad. I mean, that's like syndromic, non-syndromic, or clinically, if you're diagnosed, you can get it. So our goal is to get the broad indication and irrespective of what their genetic mutations serve them. And so we're not worried about, you know, somebody is coming with a single mutation-based gene therapies. As I mentioned before, those gene therapies, I mean, remember, the defect is there from birth. So how the dysfunctional gene or the protein expression is causing the damage to your network, people need to seriously look into that. Genes don't work in isolation. So those gene therapies, you have to be careful when you're intervening with the patients. If they do it early on, scientifically, they should get better results. Whereas we can take care of all the patients. That's our goal. I mean, ideally, any therapy, you want to give it to any patient, you want to intervene earlier than later, right? But if the patients who are in the late stage, we cannot deny them because we are able to show in our clinical trials, even the later stage patients are benefiting. So for them, it's all relative, right, Annabelle? I mean, if you think, if I'm able to keep my central vision, that's like one of our patients says, I'll be gold. If I can just hang on to what I have, because I learned how to live with this. I don't want to go further down. And so that's our goal, you know? I mean, we don't want to deny anyone. We want to have broad RP indications to take care of all the patients globally.

Annabelle Ayer, Analyst — Barclays

Can you remind us how big your actual trial is and how many patients were able to be enrolled in the expanded access?

Shankar Musunuri, Chairman

Our actual trial is 140 patients. It's two to one ratio. That means a treated group has two to one. I mean, you take like around little, like 95 and treated and the rest of them in untreated group control. I mean, so that's the design we had, which you had 140 patients.

Annabelle Ayer, Analyst — Barclays

and and who have how many have been able to get access to the expanded access program yeah

Shankar Musunuri, Chairman

expanded access program i mean we didn't publicly disclose the numbers that uh protocol can go up

Annabelle Ayer, Analyst — Barclays

to 75 patients and does that include can that be included in your bla package at all i mean

Shankar Musunuri, Chairman

obviously we have to monitor those patients um i i mean the the approval is based on the clinical trial, the phase three, this can be added as an additional data, obviously, just like phase one, two, all the data will be submitted for safety or any signals. We'll definitely summarize all that.

Annabelle Ayer, Analyst — Barclays

Got it. And with the phase three that are coming out in first quarter, you can already submit a rolling BLA. So what is it that you can start with in terms of the submission?

Shankar Musunuri, Chairman

Yes. I mean, I think that's an advantage for the company and also the agency, right? So we're able to submit a non-clinical module, and we're on target with our PPQ runs, successful, and therefore we'll be able to drop the CMC section this year. I mean, that's a big lift from any biotech company perspective. We also minimized any risk to our two phase threes for RP and StarGuard. We introduced actually two commercial scale lots in our phase three to minimize any risk to CMC. We are very robust in our CMC process. And so those two sections can be dropped in this year. So that way, as soon as the clinical data comes out in first quarter, once the top line comes in, within weeks, we can drop the clinical module. So that's the plan for rolling submission.

Annabelle Ayer, Analyst — Barclays

Great. So I just wanted to move to StarGars really quickly. Obviously, that's another genetic disease. The approach here, this is a much more homogeneous group. and your endpoints are a little bit different. You're trying to change the progression of the lesion. Can you actually reverse the lesion or once they have a lesion, those cells are completely dead. So what is the approach here? You're just trying to slow the progression of lesion expansion, correct?

Shankar Musunuri, Chairman

I think in the clinical trial, all our clinical trials are one year because there's significant unmet medical need. Other companies may be doing two-year, three-year trials. But if you're able to show treatment benefit in one year and you have unmet medical need, I mean, obviously agencies, FDA may support it, right? They don't want to keep doing two or three year trials. So in this one year, what is the measurable effect you can show compared to untreated run? That's a lesion. I mean, based on the disease progression, we can show that. So you're slowing down the growth of the lesion compared to untreated control. Of course, you'll have other measures that are going to have visual equity and ellipsoid zone, but the nature of the disease progression is slow. So obviously, we picked the primary endpoint, which is important for approval, is lesion. And so if you are seeing other effects, what I was talking about, some of the patient videos, it takes time for them to show that, like second year, third year, these patients are improving further and further, not just slowing down lesion, and they're able to see clearly, you know, their vision is coming back. You know, somebody will be able to see the faces very clearly, which was lagging before. or that's more than just controlling the inner growth of the lesion.

Annabelle Ayer, Analyst — Barclays

We're not measuring in the clinical trial.

Shankar Musunuri, Chairman

Obviously, like all our gene therapies, we have to monitor them for safety for five years, every year on annual basis. So when they come to doctor's office, some of these measures we observe. And obviously, with all our BLA filings, if we have early stage clinical trial data, phase one or phase one, two, and whatever data we have, or if you have three-year data like we released for RP, or four years, we'll put that. And all the data will be there in our BLA submission.

Annabelle Ayer, Analyst — Barclays

Okay, great, and then you have an interim analysis coming up for the phase two, three. How is it powered and what are you looking for in your decision tree? What are the possibilities here? And just maybe you can talk about that a little bit.

Shankar Musunuri, Chairman

I mean, all our trials are powered in about 90% or in some cases, RP has 95% or more, even GA. However, what we're looking for is, it's really important. I mean, it's really fortunate to have this adaptive design. I mean, during phase three clinical trial, when you're doing the registration trial, you're able to, I mean, not like a broad look, but under very strict guidance of data monitoring committee, and they can take a look because in phase one, you have a contralateral eye. In phase two, three registration trial, you got actual true controller, untreated controller. So you're really getting actual data compared to that, and now you have ability to adjust. So what are the potential outcomes? They look at it and say, based on predictive analytics, at 50% reaching eight months, in 12 months, it's going to hit it, no change needed, or you need to size up. So that'll be, I mean, if you size it up, add more patients, or in some cases, if you extend from, add another time point from 12 to 16 months, that may also help based on predictive analytics. So all these outcome analysis of predictive analytics is based to minimize the risk, further risk for the ongoing phase three with the true control data. When you have that option, I mean, it's really a very good gift for any company. So minimize any phase three clinical trial risk during phase three clinical trial.

Annabelle Ayer, Analyst — Barclays

If in this interim analysis you're given the green light to continue, those 50% of the patients you're seeing separation, you don't need to size up, you can stop the trial there, but will the FDA seek perhaps an additional study, more patients, because perhaps the 50% of that trial is not enough? Like, will you continue to enroll that trial based on the 140, or will you stop right there and try to file?

Shankar Musunuri, Chairman

No, I think RP, we don't have interim analysis. We're ending, like, all the patients completing one year.

Annabelle Ayer, Analyst — Barclays

Sorry, I've got that. Stargard is only 50% in eight months.

Shankar Musunuri, Chairman

Our endpoint is actually one year, so we have to continue. Even though the data comes out good, I mean, we continue, and we close it out at 12 months. whereas in a geographic atrophy, obviously, that's the package we submitted to FDA and EMA, 300-patient trial, and that one has a different adaptive design. When 150 patients reach one year, I mean, that trial has a very good power. I mean, even at 150 patients, I think for the primary endpoint lesion, I think our power is more than 90 percent. So that one has an opportunity, you know, does it, if it hits it, you know, there may be a potential to talk to the agency since they continue to collect the data, because it's a large disease and you need 300 patient data minimum for safety reasons. So that's how we are using adaptive design to further de-risk clinical trial, also create an upside scenario where, oh, can we file it sooner than later?

Annabelle Ayer, Analyst — Barclays

That's great. In the five seconds that we have left, unfortunately, we're out of time, but can you tell us your cash position and where that takes you to?

Shankar Musunuri, Chairman

Yeah. I mean, we recently raised the gross $130 million with Convert and with all the net and everything proceeds. Our cash runaway gets into 2028. What does it mean? That will allow us to to file two BLAs next year, and also initiate the GA phase three clinical trial to create a tremendous upbeat for the company and inflection points. And so obviously a lot of things are going to be opened up. Stargard also has a rare pediatric designation. And when you get approval in early 28, based on our plans, and the PRV could be worth $150, $200 million. And so obviously we are in a very good cash position. I mean, my team is doing a fantastic job executing. I mean, 2022, we started the first patient dose in our gene therapy trial. Today, we lead ophthalmology gene therapies because of the breadth and the depth we cover with our gene therapy is so high, large populations, significant unmet medical needs. And this cash runway will help us to really focus on programs, what we are good at in executing, and move all three programs to where they belong.

Annabelle Ayer, Analyst — Barclays

Great. Thank you so much for the time. I appreciate the overview.

Shankar Musunuri, Chairman

Thank you for having me. Excellent.