For you with too many details. We have our forward-looking statements, of course. I'll just do a quick run through the agenda. After I give a few words, we'll be watching a patient video, and then Shankar will just give a quick corporate update and a look ahead, as we anticipate 2025. Arun will dig deeper into the science of modifier gene therapy and the mechanism of action. Huma will then provide clinical trial updates across the platform. And then you'll hear from our study investigators, with new data from phase I, II for OCU400, for OCU410, and OCU410-ST.
At that point, then, we will have our panel. You'll hear from four wonderful patients. We have Manny, who is here, for our last showcase. We also have two other patients that have Stargardt disease and one patient with AMD. We'll have our investigators on stage as well so that if you have any technical questions, they can jump in, and then Mike Shine will wrap up the Ocugen piece, and he will give a commercial outlook so without further ado, I'm going to play our latest patient video featuring some of our study investigators and patients who are here with us today.
Sometimes in medicine, you see miracle treatments, and it's really my hope and belief that this new treatment can help a lot of my patients with retinitis pigmentosa. 37 years in the Postal Service. I was about 43 years old when my condition started, little by little, taking part of my vision away from me. Retinitis pigmentosa is a disease that puts a pigment in the retina, and it blocks your vision. I was diagnosed when I was in the Navy. When I look at people, I don't see people's faces if I'm 15-20 feet away, and I might just break down and cry.
It's like, why? Why do I have to be dealing with this? One thing we can't avoid is aging, and one of those problems in us, and as ophthalmologists, we see is macular degeneration. As people are living longer, they are having more and more patients with geographic atrophy, and geographic atrophy actually damages your central vision as it encroaches upon the center. You can't read, you can't drive, you can't watch television.
The current treatment and development, like, for example, gene therapy, as in the case of OCU410, has the potential to be just one treatment. So that kind of treatment is gonna be a game changer, and not only that, the complexity of treatment, which has multiple pathways, targeting all those pathways as one is very desirable as well in this case. The goal is this is gonna be a one-time treatment.
So with gene therapy, you add a normal gene to the retina and use the cells in the eye to be the machine for the normal gene and protein. And the benefit with the OCU400 treatment is that it's gene agnostic. So that means that it doesn't matter what specific gene is causing your form of retinitis pigmentosa. The fact that we're able to slow down or stop conditions that you knew five years ago was going to end in blindness, while it's not good enough 'cause it'd be nice to give them normal vision, I mean, it's borderline miraculous. I was able to see right here this movement on my hand. I didn't use to see it. Now I can see the movement. Sorry. All my life, I knew about this illness. And now I have a hope. Wow.
Good morning, everyone. Thank you all for coming to Ocugen Clinical Showcase. So excited today. Thanks to our patients, investigators, and the Ocugen team. And I think I welcome all of you. We have an exciting day today. Our superstar is going to be our patients. And that day, I think you saw the agenda, it's going to conclude with the patient panel with our investigators. We are very excited today, and we're going to share clinical data, new data from all our gene therapy programs. As Ocugen, we have established ourselves. I believe we are a leading gene therapy company in ophthalmology for treatment of blindness diseases. The three programs we have encompass many blindness diseases. Our hope is in the next three to five years, forge ahead, get the approvals as expected, and launch these products and try to help the patients globally.
Our mission is not only getting these cutting-edge technologies to the market, work even harder to provide global market access to patients who need them, irrespective of where they live. It could be in the United States, it could be in Japan, it could be somewhere in Asia, Africa, or South America. Our goal is to work harder to provide the market access. With that said, where are we as a company? We were founded in 2013. We have two locations very close to each other in Malvern, Pennsylvania. One is our head office building. Adjacent to that, very close by, we have a manufacturing facility we built for our cell and gene therapies. We also have a business center we opened in India to efficiently manage the operations to support our U.S. development and clinical team.
We do have core values as a company: respect, integrity, teamwork, and accountability, which is extremely important because we are in the business of impacting lives. Whatever we do, quality comes first for us, and we need to manage with high integrity. That's really important for all our employees. I mean, it's. It goes across the pharmaceutical industry because we deal with people's lives, nothing else. With that said, again, we are doing well as a public company. We are listed on Nasdaq. With that, I'm going to give you we have first-in-class gene therapy platform, modifier genes, targeting OCU400. The phase III is going well. Huma is going to talk about it. Our goal is to efficiently recruit all the patients we need by first half of next year so that we're on target for approvals in late 2026.
That means our filings have to start rolling submissions sometime late next year, and they're followed by closing the clinical sections in first half of 2026. We do have orphan drug designations in with FDA and EMA that'll give us an accelerated path. OCU410, targeting geographic atrophy, late stage of dry age-related macular degeneraton, is going through phase II. And today, we're going to discuss preliminary efficacy and safety data from phase I. OCU410-ST, we have completed dosing patients successfully in our phase I clinical trial. We're going to discuss the preliminary efficacy and safety today. We have taken a pause on this program, because of FDA guidance, changes in the last two years. They're promoting drugs for orphan diseases, especially gene therapies. There may be a potential path, converting our phase II into confirmatory pivotal trial for approval.
So we're going to take a pause and make sure we're aligned with FDA before we initiate the phase II. So that's in a nutshell. Once again, we have a lot going on at Ocugen. We've got a great team of some of the team members are gonna talk today. They don't sleep. They work tirelessly for patients. Everybody has the same mission: get these therapies to the market potentially as soon as possible and take care of, you know, patients across the globe. Thank you. With that, I'll introduce our next speaker, our Chief Scientific Officer, Dr. Arun Upadhyay.
Thank you, Shankar, and good morning, everyone. Today, I'm going to talk about our modifier gene therapy technology platform, which was developed by our inventor, Dr. Neena Haider. She's here. I’ll just, you know, of course, there is a lot of work went into it, but I'm going to give you the glimpse and potential of this technology and how we have taken this technology to the human translation. If you look at overall retinal diseases, and especially back of the eye diseases, there is a significant unmet medical need. If I have to categorize this group of retinal diseases, you can broadly categorize into two, two groups. You have inherited retinal diseases, and you have, like, age-related macular degeneration that is multifactorial disease. If you look at the landscape of inherited retinal diseases, you can see the complexity.
Look at the number of genes which can lead to this disease, so there is a significant genetic heterogeneity, and if you look at the prevalence of this, you know, all these indications, just retinitis pigmentosa in the U.S. and EU alone affects, you know, close to 3,000 individuals, and if you look at the global prevalence, it is like close to 1.6 million for RP alone, and when we look at, like, age-related macular degeneration, U.S. prevalence and EU prevalence is close to, like, you know, 19 million, and if you look at the global prevalence, it is close to, you know, 226 million, so there is a significant unmet medical need, and that goes with the Stargardt, which is also, like, you know, an inherited retinal disease, and close to 4,000 individuals are impacted in the U.S. alone with this condition.
Now, what options we have, right, available? Currently, if you look at, there is no treatment available for most of the IRDs, except one that is Luxturna approved for the treatment of RPE65 gene mutation that primarily impacts, you know, less than 2%, you know, patients in IRD. For AMD, like, you know, if you look at geographic atrophy, we have two recently approved products, you know, in the US, but still there's significant unmet medical need in this space. There is no product available in the EU, you know. The reason for that, as I say, because there's a limited treatment benefit, and there are some safety and patient compliance, which I'm going to talk about.
When you look at overall, if you know about these diseases and mutations, you know, what is really preventing us from developing therapy for these indications? Some of the key barriers when you look at, to, you know, find a therapy for these genetically diverse and multifactorial diseases are primarily driven by the high genetic heterogeneity. What does it mean? If you are taking a traditional approach to develop a therapy which is just targeting single gene or single mutation, you will have to develop 300 products if I'm talking about 300 genes implicated in IRD. It is almost an impossible task for any sponsor, you know, to take everything from discovery to the approval.
Another challenge is that, you know, our understanding that disease is driven by just a genetic mutation, probably that is not always the truth. A lot of us, we carry that genetic mutation from our birth, but not all of us manifest that disease at the time of birth, you know. And every individual has its own journey for the disease progression, you know, onset of the disease, progression rate, and severity. So there are other factors which are implicated in these, you know, complex conditions. So just correcting a single gene may not be the right approach. And then you have to think about how I'm going to holistically treat this disease. And that is where modifier gene therapy technology comes into the picture.
Another big challenge is going to be like, you know, when you talk about AMD, most of the development in the age-related macular degeneration has been primarily focused on targeting one pathway, like complement, but disease is not that simple, you know. It is very complex, so when you take the approach of targeting like single mutation, single pathway, you know that you are going to be limited by both, you know, treatment outcome in terms of benefit and, of course, some of the safety challenges as we are seeing with the currently available products, so what is modifier gene therapy technology? So it is a revolutionary approach, and why do I call it revolutionary? Because it is not like that we are just trying to treat the symptom. We are trying to treat the disease at the root.
What is really cause for the disease? And is there a way we can address the disease? That is what modifier gene therapy does, so if you look at modifier genes are basically the main control system for, you know, how the retinal cells, you know, survive and function within the eye, and it is very important that we promote the cell survival and function if we really want to preserve the vision in these patients, and another important benefit of this modifier gene therapy technology is that it is gene agnostic, as I said, so this product can be used for anyone having any genetic background or mutation. It is multifactorial also, so it can target other diseases which are non-genetic in nature, for example, geographic atrophy, and, of course, it can alter the course of disease.
That is what we are seeing in some of our patients. So it is not just pausing the progression of disease. In some of our patients, we are seeing reversal of the disease. You know, we are seeing that, you know, they are gaining certain vision. And that can happen only if there is some improvement in the retinal cell survival and function. So with that, I would also like to provide you some glimpse about, like, how we are different than other modalities we have right now in the, in the development, you know, by various companies. So if you focus, there are four different, you know, approaches, you can see is happening in the ocular space. So we have gene augmentation, we have gene editing, we have optogenetics, and we have cell therapies. Every approach has their own pros and cons.
Here, I want to highlight, you know, how they are limited and how we are different. Modifier gene therapy is different than all these four. So if you look at gene augmentation, primarily it delivers, like, you know, a normal copy of affected gene, but it is limited to treat only one gene. It is primarily applicable to monogenic condition and recessive condition. Why am I highlighting a recessive condition? Because if you have a dominant mutation, for example, Rhodopsin patients, there are so many mutations which are dominant in nature. This gene augmentation doesn't work in them because it further aggravates the disease, you know. It's not the right approach. Gene editing, again, limited by the single gene targeting at the same time.
Sometimes it is only single mutation, and sometimes in these patients, one gene, one gene can have hundreds of mutations depending on the location of the base pair. So it's pretty complex. Optogenetics, it is a technology, you know, primarily, you know, provides, you know, delivers the protein which captures the light. But this technology is very much limited to the advanced stage of the patients which are at the very much terminal stage, lost all their photoreceptors. So it has some potential, but it can, you know, primarily target only a small number of patients in the later stage. The cell therapy. Cell therapy is the other approach, you know, people are taking in this space. Primarily, you know, cell therapy can deliver the cells, but the safety is the biggest challenge.
Integration of the cells with the retina and photoreceptors is the biggest challenge in this space. All these technologies have started their journey long back, and so far, we have not seen much, much success, you know, which really translates to the human and can provide the benefit. If you look at modifier gene therapy, it is gene agnostic in nature. It targets broader patient population. It has potential for stabilization or reversal of the disease. So far, we have seen very excellent safety and tolerability profile and efficacy in the, you know, early phase of clinical development. How does this modifier gene therapy technology work? If I have to give you some pictorial representation of what I mentioned about that it does target multiple pathways and then does the resetting.
So here you can see that when we deliver the modifier gene to these retinal cells, it targets multiple pathways, like photoreceptor development, cones cell development, phototransduction, resetting the molecular network, you know, cell survival. Once you fix this pathway, that leads to the survival of retinal cells, which eventually, you know, helps with your, you know, preserving vision or improving vision in these patients. In our, like, you know, preclinical proof of concept study, we have seen this gene-agnostic benefit in multiple animal models, you know. This slide primarily highlights that whatever structural and functional parameters we looked at in all these five different animal models, OCU400 was able to, you know, preserve the retinal cells, improve the retinal cell function, and also improve some biomarkers in the retinal cells, which are indicative of retina health and function.
At the same time, we also looked at the biomarker, which clearly demonstrated the molecular resetting mechanism of the modifier gene therapy technology. With that, I'll transition into our another modifier gene therapy candidate that is OCU410 based on the RORA modifier gene. RORA is also a nuclear hormone receptor. It is a modifier gene. What it does is that it targets multiple pathways which are linked to the pathophysiology of geographic atrophy. That is lipid or drusen formation in the retinal cells, inflammation, complement pathway, and the oxidative stress pathway. This is some of our proof of concept data in the animal model as well as in vitro model. As you can see on this slide, OCU410 molecule basically has an anti-drusen activity.
In the animal model of macular degeneration, ABCA4 knockout mice, it was able to significantly reduce the drusen formation. It was able to control the pro-inflammatory cytokines, so significant reduction of inflammation. It was able to provide, you know, a protection of the retinal cell survival under oxidative stress condition. And it was able to basically upregulate the anti-complement protein. And why it is important? Because complement drives the degeneration of photoreceptors. So if you can prevent the complement complex formation, then survival of the retinal cells can be improved. So with that, what I would like to highlight here is that OCU410, it has a multifactorial target. It targets, you know, all these four pathways which are linked to the disease pathophysiology of the AMD. And also, it is a potential one-time therapy.
So if you look at currently approved product, you know, you have to, like, you know, patient has to get either six to 12 injections per year. Not only that, there are some safety concerns related to induction of, you know, CNV. And also, they have a very limited effect. You know, their effect is very much minimized to the structural benefit, you know, slowing the progression of disease, like marginally, you know. However, OCU410 has a potential to not only just provide a structural benefit but also, you know, provide some, you know, functional improvement in their vision. That's our hope. And these are some of the products in the market, as I was mentioning.
If you look at some of the latest, latest stage assets in the GA or approved product, you can see here that most of these products, they target only one pathway, whereas OCU400 targets all the pathways which are linked with the disease pathophysiology. Same molecule, OCU400, RORA, we are also developing for a Stargardt patient. And the reason for that is that Stargardt and geographic atrophy, they share the similar disease pathophysiology. They have the different, you know, basis for disease induction. One is age-related, one is genetic disorder caused by mutation in ABCA4 gene. So our all the proof of concept animal data is coming from the ABCA4 mice model. So it is basically a direct translation from animal model to the Stargardt patient model.
That's why we are also doing the clinical study in a Stargardt patient. Currently, we have completed phase I, as Shankar mentioned, and we are, you know, going to have interaction with, you know, regulatory agency to work on our plan to develop a clinical design which can be potentially used for the approval of product, you know, in the U.S. With that, I would like to invite our Chief Medical Officer, Huma Qamar, to provide you some clinical update.
Good morning, everyone. It's a beautiful morning in New York and seeing our patients, superstars, investigators, and our team at Ocugen and analysts and everybody here today. Thank you very much for all your help and support. It's kind of like an emotional day for me too because, you know, when you are overseeing a program, you're, you know, looking at the data finally coming out, and that's exactly, you know, you're interacting with the patients, and, everything that you do has a meaning, has a potential, way of addressing the unmet medical needs of the patients.
So I am very proud to present, some of the updates that we have been working on, day and night diligently at Ocugen. So in terms of, our OCU400, that's a novel modifier gene therapy, created by our very own Dr. Neena Haider. What is it? What we were doing? We have, you have all heard about that. So, some of the things that we have achieved in the previous quarters is that that's the only first phase three novel modifier gene therapy clinical trial which has a broader retinitis pigmentosa indication.
What does it mean? It is that it will have an impact on the 98% of the mutations that cause retinitis pigmentosa to have a potential treatment. And currently, we are running our phase three trial. We are on track for our commercialization, BLA, and MAA in 2026. And we are also on track in completing our enrollment in the first half of 2026. Not only that, one of the exciting news that we have shared with the markets and with everybody in the past few quarters is that we have initiated our expanded access program for OCU400.
Anyone that cannot meet the inclusion/exclusion criteria of OCU400 will be able to actually enroll in the expanded access program. So that's great news. We are the only company to have that. So that is one thing that I would like to highlight. Not only that, we got the Health Canada approval for our phase III as well as, so now we have almost 15 centers per our protocol and up to five centers in Canada that we will be recruiting. So almost 15 centers in North America. So in terms of OCU410, you have heard about the great mechanism of action of RORA, and that's a single injection approach, a subretinal injection, which is for life, and that is for geographic atrophy secondary to dry age-related macular degeneration. If you look at the stats, we all know it.
We have two approved products, which require a lot of compliance: 6-12 injections. Arun has very well presented in the last few slides. But if you look at that dry AMD affects nearly 19 million people in the U.S. and Europe, and let alone geographic atrophy affects 2 million-3 million people in the U.S. and Europe. And technically, it's a significant market opportunity, not only from the clinical side but also from the commercial perspective, as well. So what we have done is that we have a phase I, II ArMaDa trial. We have successfully completed our phase II, and I'm proud to share that there are no serious adverse events related to the investigational product for OCU410. And currently, our phase ii is underway.
We have the clinical trial design that we will go in detail, but I'll just give you a little bit of updates on that as well, that it's a one-on-one, one-on-one design where we have a high dose, medium dose, and a control group, and we are on track in terms of the recruitment and completing the OCU410 phase I, II overall enrollment. So last but not the least, OCU410-ST, we have you know a couple of patients here today too that you will be talking to, and we will be sharing their experiences as well. However, there is no approved product for this inherited retinal disease, and that gives us the hope that we have successfully completed our phase I portion of the study and also single subretinal injection for life. There are no serious adverse events related to OCU410-ST as well.
Currently, we will be looking at the phase two portion of the study where we are actually looking to have the concurrence with FDA for a confirmatory trial for final approval as well. Just to give you a snapshot on the ocular programs, OCU400, as we have talked about throughout, we have excellent safety and tolerability profile, no serious adverse events related to the investigational product, OCU410 GA and SD, and also 400. We are now in the phase three on track. As well as another thing that I would like to highlight today is that, I've been getting questions on the Leber congenital amaurosis as well. That was, we had actually dosed the patients from phase I/II , and today we will be sharing some updates from the phase I/II as well.
The investigators will go in detail, but overall, if you look at it, we were able to demonstrate in the treated eyes stabilization or preservation of 67% in the visual function. That's best corrected visual acuity. That's the vision chart that you see in the optometrist's office, for pediatric patients at nine months and adults at 12 months. Also, not only that, we were able to show 100% stabilization or improvement in FST in the pediatric patients at nine months and adults at 12 months as well. Overall, improved quality of life. We have the National Eye Institute Quality of Life Visual Function Questionnaire, and that was also demonstrated in adult subjects at nine months and 12 months time point. In terms of OCU410 and for GA, as I have mentioned, that we are on track for our completion for phase two as well.
And the safety and tolerability profile has been excellent. Not only that, it's a one-time subretinal injection for life as compared to the approved products that have potential side effects that we have shown in the previous slide and the compliance as well. What we have demonstrated here with our product is that it slowed GA lesion growth in treated eyes versus untreated eyes at six months. And not only that, the low dose demonstrates treatment benefit in by stabilization of visual function, LLVA at six months. That is a very important point to consider because currently the approved products have not demonstrated the visual function. They didn't get the approval on that. They got the approval on the structural, but we are demonstrating both here and in Europe there is no approved product because of the limitation on the visual function.
Last but not the least, OCU410ST, there are no current therapies, as I've mentioned. Safety looks and tolerability looks very favorable. The treated eyes show or demonstrate 84% of the lesion growth with treated versus untreated and up to 80% preservation of retinal structure at six months and visual function 60% at of the BCVA at six months as well. So these are all the updates from the clinical trial updates. And actually, I would like to now call upon Dr. Benjamin Bakall, who is the Director of Clinical Research at Associated Retina Consultants and Clinical Assistant Professor at University of Arizona College of Medicine, Phoenix, to provide the updates on phase I/II OCU400 study.
Great. Well, thank you very much. It's nice to be in New York. You're coming from Arizona. It's a little cooler here than back in the desert. I'm originally from Sweden, if you detect an accent. I'm gonna talk to you about the not previously released data from the CEP290 part of the OCU400 treatment. As you know, the phase II study included 18 patients with retinitis pigmentosa and two patients with Leber congenital amaurosis. Two adults, two pediatric patients. The goal with the treatment was to evaluate the safety and efficacy of OCU400 in this cohort, Leber congenital amaurosis, and yeah, mutation is CEP290 gene. The reason this gene was selected was based on the preclinical data from the animal studies. As we heard, OCU400 is a novel modifier gene therapy and has, you know, really solid preclinical data from the retinitis pigmentosa cohort.
So very similar, the gene was delivered with subretinal delivery, one-time treatment. The dose that was selected was the medium dose, to overexpress the protein NR2E3. And that's kind of the how phaseI , II trials are designed. You have a dose escalation. You try to find out what's the right dose to treat. All these patients had a medium dose. And we evaluated the safety outcomes in these four subjects. So we have month nine data efficacy that's gonna be presented for all the subjects. We only have the month 12 data for one subject who's an adult patient. One subject, adult, developed complication not related to the product but developed retinal detachment. That caused loss of vision. So we can't really include all the data from that eye because of the retinal detachment.
And one patient, a pediatric, after nine months or so, developed high pressure or developed glaucoma, which is a condition that's related to pressure. So we only have data up to nine months for that patient. After that, we can't really include it. We think that the reason glaucoma was developed was because of steroid treatment, not because of the product itself. So yeah. The outcomes presented here will be the best corrected visual acuity, the National Eye Institute Visual Quality of Life Questionnaire, Full Field Stimulus Threshold Testing, which is kind of a dark adaptation test, and a mobility test. That mobility test was the same that was used for the gene therapy that you've heard about before, like Luxturna.
It's similar kind of a maze, walking around in different levels of light. The data that I present here, if you look on the left panel, you can see the change in the visual acuity. Only the one adult patient could, because this is a patient with very poor vision. Only the adult patient could read the ETDRS chart. Those are the regular eye chart that you see in an eye clinic. If the solid blue line is the treated eye, and the dotted line is the untreated eye. You can see that over time, the treated eye improved and then decreases down back to baseline. However, the dotted line shows reduction in the visual acuity below five letters, which is a threshold cutoff.
We know that these conditions are slowly progressive. There is a progression of the vision change over time in untreated eye. Looking at the right panel, that's the pediatric subjects. They could not see the ETDRS line, so we had to use it. It's called the Berkeley Rudimentary Vision Test. It's a lower level scale. For the patient one, the pediatric patient one, there's really no change in either eye over this course. So really kind of stable. Then in this graph going up is worse vision. So the treated eye initially had reduced vision, but then at month nine, came back to baseline. The untreated eye for patient two, the pediatric group again, at month six was stable, but then at month nine, it deteriorated.
So, you know, in summary, two out of three patients that we present here, of these LCA, they had stabilization or preservation of the visual function on these visual acuity tests. And then going on to the next slide. So here we're talking about that this test is, it's called FST, full-field stimulus threshold. It's a dark adaptation test. We're seeing what's the lowest level of light a person can see. So it's a, this is a standard test that's also been done in the Luxturna treatment trials, for example. So if you look at the left panel, and here, it's a little confusing, but improvement is going down. So looking at the bars, improvement is better. So these are different kinds of stimuli that's presented for the dark adaptation. So dark adapted white, blue, or red light.
You can see that the treated eye in the blue bars is - 1.3. So improvement, detecting red light, that means that the cone photoreceptor, they can see red. Rods cannot see red. So the cone photoreceptor function improved somewhat. It didn't really reach the threshold for the red stimulus. And look, we only have, you know, we only have data for one pediatric patient because the second pediatric patient has so poor vision because of nystagmus, so couldn't perform the test reliably. But this one pediatric patient had also improved the dark adapted red stimulus, much better than the adult. So it reached a threshold, even for the blue stimulus, which involves the rods. So there is some improvement. So both these patients showed stabilization and improvement overall cone response function.
The cones, as we know, are important for daytime vision, color vision. But still, this is a very severe disease to begin with. If we can improve the cone function, that's very positive. Okay. I'm going on. I'm gonna summarize here. You know, as I mentioned before, OCU400 is generally safe and well tolerated in these LCA subjects. We didn't find any severe adverse events related to the study drug. As I mentioned, there was a retinal detachment. We think that's because of the surgery. One patient developed glaucoma, but that was, you know, most likely due to steroid treatment, you know, after nine months or so. Then what's positive is that one adult LCA patient showed one lux level improvement in mobility test, reaching from the levels of 130 lux to 50 lux at 12 months.
We also saw stabilization of the visual acuity, improvement in overall response of the cone response at 12 months. And then, yeah, summarizing again, 67% of these patients or, you know, two out of three had stabilization or preservation of visual function on the visual acuity. Yeah, overall demonstration of the cone function, as I mentioned. And then, the NEI visual function quality score, the one adult patient, had improvement. The second adult patient, even though he had retinal detachment, he reported improvement, but you know, you have to take that with a grain of salt, because we can't really take those results into consideration because he has retinal detachment and surgeries. Yeah. So that's kind of pretty much concludes my part of the talk. And I'll be happy to answer more questions later on. Thank you.
Thank you, Dr. Bakall. So I would like to actually request Dr. Syed Shah, who is our Vitreoretinal Diseases and Surgery Emplify Health Vice Chair for Research and Digital Health at Gundersen Health System, La Crosse, Wisconsin. He will be discussing the updates from our OCU410 Phase I/II trial. Thank you.
Thank you, Dr. Qamar. I wanna give special thanks to all the patients whose participation in these trials makes the science go forward. Also to the company management who take chance and investigate and invest into product, which is life-changer for a lot of patients which are actually sitting here. Thank you to my wonderful patient here as well, who was part of the trial. I'll start from here. So all of us know already what geographic atrophy is. We talked about it. We know the burden of that globally, not just in the U.S., everywhere else.
So I'm gonna focus on the trial itself for now. So the first part of the trial was a dose escalating study, phase I, in which we have three different doses to try. As my predecessor pointed out, that you design a dose escalation trial to make sure you find the best match of safety and efficacy to use in a later phase trials. This was the key inclusion exclusion criteria of the patients who were macular degeneration with geographic atrophy. We had a specific GA lesion area, which we wanted to investigate and see if that increases or decreases or slows down the increase in the area of that lesion. And the key exclusion criteria listed over there as well. This was followed, being followed right now in the phase 2 dose expansion, in which you have a medium and high dose being tried against control group.
This will give us a firsthand, head-to-head comparison of treated versus untreated eyes, and these are just some of the primary endpoints. Of course, safety is a paramount thing, and primary endpoints are all related to safety, but we also are exploring secondary endpoints, some of which we will talk about today, which includes the efficacy, meaning change in the GA lesion size over time, and then there are certain exploratory endpoints as well, which include the functional testing, which is low luminance vision as well as microperimetry and drusen volume, which is a structural test, but one thing that Dr. Qamar also mentioned over here is that one more thing I wanna add, that CNV in the fellow eye was not an exclusion criteria. So we did include the patients who, in the untreated eye, have choroidal neovascular membranes.
But the one thing which we highlighted, before me as well, we were not, we did not find any serious adverse events related to the drug itself. So it was found in the dose escalation phase to be pretty safe to move on to the phase III trial as well. And some of the reported side effects with a new treatment, especially injectable, with a subretinal injection granted, are optic neuropathy, which is reported in other treatments, vasculitis, endophthalmitis, or choroidal neovascularization in the beginning of the patients that we have enrolled. So the next thing I wanna highlight over here is that treated versus untreated and natural history study.
You can see that at six months. Now granted, at three months we have five patients, and at six months we have three patients because that's the data we had available for all the patients who had completed the six months. And as you can see that there was a 21.4% reduction in the rate of progression of geographic atrophy. And this is actually more than what's reported in the anti-complement treatments already available in the market. And you can see that the slope of the untreated eye overlaps with the natural history of the disease, while the treated eye does much better. Again, more than what's available in the market at the moment right now.
So the second thing we wanted to see was a quick look at the publicly available data for the Syfovre or the new treatment, which is anti-complement, every other month treatment at six months and every month treatment at six months. This shows the difference between the GA lesion treated and untreated eyes. All right? So this means this much more tissue was preserved in the treated eyes. The treated eyes had this much more tissue at the end of certain time points as opposed to the untreated eyes. Now, if you look at the OCU410 at three months, it is almost equal to the Syfovre, every other month treatment at six months. So at three months, the drug was able to demonstrate in the patients we had tested that it's equal to the Syfovre or every other month treatment.
If you look at the six months data, it beat both the three months, six months, every other month, as well as the per month. This initial results from this were able to show that the GA, more tissue is preserved. In other words, more of the retinal tissue is preserved in the patients at six months, more than, more than both the PEOM as well as, I'm gonna go back. Is it one way only or no, it goes back? There you go. It clearly shows that there is a difference at six months when it's compared to the anti-complement available in the market. Second thing, we also looked at the low luminance visual function. Visual function has become very important because at the end of the day, it is the functioning of the patient.
As you may also recall in retinitis pigmentosa, we have a maze in which the patients are tested in how well they do in low luminance conditions, daily activities like walking and going through obstacles. The same concept applies in geographic atrophy, in which we use low luminance visual function or visual acuity for the patients, and we had shown that there was stability at six months among all the patients who were treated with OCU410, and 100% of them, all three of them, and lastly, I would summarize this by saying the first and foremost thing was very safe. We did not find any side effects related to the drug itself. Second thing is that the treated eyes had a 21.4% decrease in lesion size growth, which is more than what anti-complement has shown in published data over two or three years.
This is at six months, mind you. And then all of 100% of patients had stabilization of visual function. And the single injection, and keep in mind this is just one injection of the monthly or every other month injection, it was able to preserve more tissue around the lesion or its expansion was slowed down in all the patients we have shown over here today. And that way it preserves more of the RPE cells and on top of them the photoreceptor cells as well. So with this, I will end and, we'll let Dr. Qamar take over and invite the next speaker. Thank you, everybody, for coming today.
Thank you, Dr. Shah. That was exciting updates. So now I would like to call upon Dr. Lejla, and she's going to present on phase I/II, Stargardt disease. She's the director. She has a lot of credentials, so I have to, like, go through all of this. Director, Duke Surgical Vitreoretinal Fellowship Program, Professor, full Professor of Ophthalmology with Tenure Adult and Pediatric Vitreoretinal Surgery and Disease, Duke University Eye Center, and Retina Scientific Advisory Board, of Ocugen as well. She's a chair. And, I just want to thank her personally, the day we have started our OCU400 novel modifier gene therapy trial. She has been vital in, our programs, particularly from the surgical aspect as well. And I cannot thank her enough, for all the great work that she has done and has supported Ocugen throughout in all these years. So over to you, Lejla.
Thank you, Jovan. That was, very kind of you. Appreciate that. Super excited to be here as well with all of you. First of all, it's exciting to hear these first ever updates and all of the programs that Ocugen is leading. It's exciting to have options and one-time treatment option for our patients. So truly, seeing the data released today, it's been just exciting because of the overall enrollment process and as well as progress that we see.
As a retina specialist at Duke University, I am involved in quite a few clinical trials. Primarily, my interest is in gene therapy trials. So I've been very excited to be part of this program and kind of see the progress that it has made so far. I'm gonna cover for you OCU410ST phaseI , two study. And just like the other ones, we're covering the phase I , two phase I data. It is a dose escalating trial.
We are doing a preliminary time points here with low dose and medium dose. Each dose, enrolled three patients before proceeding to the next level. All doses was approved by DSMB, before initiation. Currently, we are sharing with you the available time points, which is for low dose and medium dose. We're focusing on six patients all throughout. I do wanna point out the primary endpoint, just like other safety trials, or phase I trials is safety. We wanna make sure we address those and talk about those. Then secondary endpoints, we clearly wanna see efficacy as well, efficacy in terms of visual acuity, but also other changes, especially on OCT. The key inclusion exclusion criteria are typical of any inherited retinal disease. We wanna make sure there's no other ocular diseases patient is fit for surgical intervention.
And clearly, there's no neovascularization as well, so overall safety in the patients thus far in the phase I is quite favorable, so no study drug-related events were reported, none deemed study drug or procedure-related, so no development of exudation, infection, inflammation, anterior ischemic optic neuropathy, or vasculitis, and there were no other events of special interest either. In terms of efficacy, the early data does show in the and these are available time points, so we're sharing with you early time points, but clearly what's available to us, and it's exciting to see in these early time points efficacy as well. We're comparing it between the treated eye and untreated eye, and we're looking at six-month data for the low dose, two patients in that group, and medium dose, one patient data point available.
It's exciting to see that the growth of atrophic area is significantly different at a slower rate, compared to treatment and untreated. That difference is 84%. Clearly, small numbers, but exciting to see such a large difference between the treated and untreated eye. In terms of retinal preservation or structural and visual function presentation, as you all may be aware, we're more and more talking about this in geographic atrophy, especially with the currently approved therapies. We do know the visual acuity is not the only answer in these diseases. Similar inherited retinal diseases, we're more and more talking about preservation of tissue and decreasing, yes, growth of that atrophic area, but really preserving retinal function, which will lead to visual function as well. In all of these, you'll see that there is definitely preservation of tissue.
There's not only decreasing the growth of the lesion, but that is leading to retinal thickness stabilization to improvement, visual function improvement, and overall macular volume is stable to improved. So what are the numbers like? The atrophic lesion growth has decreased, as I showed to you, 84%, 84% between treated and untreated eye. Four out of five or 80% of treated eyes demonstrated preservation of macular volume on OCT readings, and three out of the five or 60% of those treated eyes demonstrated preservation of retinal thickness overall. This is leading to visual function improvement. And about three out of the five patients we're sharing with you today that's 60, that is 60% have demonstrated stabilization to improvement in visual function as well. So clearly, very exciting early data demonstrating quite favorable safety as well as durability thus far in this low to medium dose.
We do show that there's stabilization to improvement visual function, retinal outcomes. It's exciting to kind of forge forward to the phase II. As was shared with you, there's gonna be FDA discussion to further use that trial as a complementary trial in the future, so thank you so much for your time. I'll turn it over to probably the best part of this program today, the patient panel.
Okay. The stage crew is gonna put the next scene up here. I'm going to introduce our analyst from Chardan, Dr. Daniil Gataulin. He's senior research analyst of biotechnology. We'll have each of our patients start to come up to the stage, please. Then, Dr. Breininger, Dr. Shah, back on the call. Do you want to take the stand on the answer? Okay. Please. Please be fine to take commentary. Medical commentary.
Thank you. Thank you. Thank you. Great. Thank you, everyone. Thank you, Tiffany, and thank you, Ocugen, for giving me this opportunity to lead this panel. It's an honor to speak with patients. The purpose of this panel is to really focus on patient experience. We are not trying to dig into science and their understanding of the disease at the molecular level. We have KOLs and we have company representatives to address those questions. But I really wanna talk to the patients and walk through their experience, from early days when they first started noticing changes in their vision to their experience going through those clinical trials.
So to introduce the patients, from the side closer to me, we have Liz, then we have Mary, Manny, and Adam. Thank you for joining us. So to start things off, can you tell us a little bit about your experience, from the moment that you noticed the changes in your vision, the doctor appointments that you went through, and the moment you received the diagnosis and what that meant for you? We'll start here.
Yeah. Sure. Okay. My name's Liz. I have Stargardt disease. I went to several eye doctors growing up for contact and regular glasses appointments. So around the year 2013, they started to notice drusen on my retina and asked me to follow up with an ophthalmologist. So I went for several appointments over the last eight to nine years to ophthalmologists, different ones. They just kept monitoring the status of my retina.
They said, "No changes, no changes, everything's good." Then at the beginning of 2023, I noticed that my vision was declining significantly. I went to get another opinion at an ophthalmologist. Wills Eye Hospital in Philadelphia ended up doing a genetic testing after I asked them, "It could potentially be Stargardt's, and I've heard that before, so could we take a look at that?" They did a genetic test on me, and it came back for Stargardt's. From there, I didn't know of my options. I was told that there are no treatments out there for me. For someone with my condition, there's nothing approved for me. Having a background in clinical research myself, I sort of took it into my own hands.
I had a list of clinical trials available to me, and I did my research on the clinical trials website, you know, all the information available to a patient like me. I came across the Ocugen trial. I was first going to enroll in a trial with a very high dose of vitamin A, which could be dangerous, and that was one of the only other options to me, so then I found the Ocugen trial. I reached out to the site contact for the only open site at the time.
They were so communicative. They were such great understanding people, very open to answering any of my questions. That made me feel, as a patient, very safe and very comfortable to move forward with gene therapy being so, you know, promising. I thought that was the best way to go. So from, you know, 2013 to when they first started to notice something in my eyes until now, I think that it was big progress for me, so.
Great. Thank you, Liz. Mary, Mary, please.
My name's Mary Markle. I don't have exact dates here, but it was 15-20 years ago that I went to my eye appointment. We go every year. And the doctor said that you have the beginning of macular degeneration. He had noticed one little drusen. I didn't have anything that was affecting my eyes probably for another 10 years or longer. It was very slow. I knew about this disease because my mother has it, and she went for her appointments. And my mother, at the age of 90, she did not see very well. I was not looking forward to anything like that.
So whenever I would go to an appointment, they would check me, and I would ask, "Is there anything out there that can help me yet?" And a few years ago, we had to switch doctors, and it was an Angela Darbo. And I'm not saying the other doctors wouldn't have, but she is the person that was keeping track of it for me. She was watching for anything that might come up and help me. And she mentioned Dr. Shah would be somebody that I could see at the main clinic in La Crosse, Gundersen Clinic. So eventually, he liked the Ocugen 410 trial. So an appointment was made for me right away so that I could get over there and see him.
I looked it up on the internet, and I wanna know everything I could about OCU410 so that I could be informed and talk with him and just know what I was talking about and everything. When I saw Dr. Shah, I met the physical requirements that you need to have, and my eye was in the condition that you needed to have for it and everything else. He was going to explain it to me. He did do some really good explanations as far as just what it's all about. I did tell him that I have looked up the OCU410, and I know a lot about it. Yes, I'm very interested in being a part of this study.
They did not have the applications ready yet, but he said, "When we have applications, we'll get one to you." From that moment on, I felt pretty confident that they would accept me and was certainly hoping they would accept me. Yes, I was accepted for the OCU410 trial. I don't know if that was in the question, but the first time that I actually realized I had the symptoms was probably about, I don't know, anywhere from five to 10 years ago. I was looking at the sky at night, and we had a place in the country, and so you could see all the sky. I saw stars, but when I wanted to look directly up at the stars, there was a gray cloud, and there were no stars.
It's like, "Well, I'm sure I saw stars up there." And sure enough, yeah, there are stars over here. But when I wanted to look over here, there were no stars. So that was like, "Oh, is this ever interesting?" Is it good? No. But it was interesting. So anyhow, that was, and in the evening, if I'm in my house and I'm looking up at the ceiling, and it's gotta be darker out. Daytime, it's no problem. I don't have this. But we have the ceiling fan, and I'll look up at it, and it's like, "Where is the fan? Where are the blades?" And I turn my head a little bit, and there's one of the blades. It's just, that's what I've been seeing, and that's some of the first things that I've been noticing.
Okay. Thank you, Mary. Manny?
Well, thank you. I thank all of you for being here and interested to hear about our disease, the company. I'm very grateful to them. I've been in other studies already, and none of them have worked. I knew about retinitis pigmentosa very, very early in my life. My grandparents, my grandfather, my uncles, my aunt, they all had the disease. I knew early on that there was no cure for it. So in a way, I was ready for whatever the world will bring me. That was back in Cuba. I went to the best doctors in Cuba. There was no cure. I came. I began to study or begin going to be a patient at Bascom Palmer, which is a top-of-the-line hospital for the eyes. I've been in two other studies before this one. They canceled it one, maybe a few months, when they started.
And the other one took a year, and they dropped it because there was no signs of improvement. So two years ago, somebody called us from the hospital asking if I wanted to be in another study. So when we started talking, I started to beginning to like what I was hearing, the way the study. So I went in. I did all the preliminaries, and I started the study. Actually, my brother also got involved because we both have the same situation. And at the beginning, it was I didn't see anything, you know? It took 40. It took 20 years. When I was 40, 43, my eyes started getting the and the pigments in it. So I had no problem driving. I'd have no problem, you know, doing anything. But as my age started going, I started seeing declining on my eyesight.
So that's when I started getting worried. Well, this study today, I can only see through two channels. Everything else is blind. And, can I do the what I? Please. Okay. Everybody has a piece of paper there. I wanna do something because that's the best way I can do it. Can you give me more? And the pencil? I got it. Oh, I got my flashlight. I want you if anybody was here last February? Good. I want you to draw an eye on this corner, please. Everybody. This is Ocugen 101. And I want you to draw a hole into your eyes. Punch it. Punch a hole. In one corner or two holes? In the corner? In two corners. Two holes? That's my eye, okay?
Now, I want you to do this for me. Put it on your eye and look at me. A little bigger if you can because I can see a little bit big. You can see me, right? Yes. Thank you, honey. Now, that's my vision. Today, I never told the company about it. I want you to, on the second, another eye and do the same. This time, fold it and put it next to you like this. I don't know, it's gonna take too long, but I can see through this side now. I drive. I still drive a car right around the neighborhood. February, I could see this year. I could see a shadow here. Now, after we came from the meeting, February, March, I don't know when. I can't remember.
I was driving home, and scared the hell out of me because I saw a car going by, which I could never see before, okay? So, I mean, if it's not good, I don't know what it is. I thank the company for doing this to us. It's giving us. I'm 70 years old. We love to travel. This year, two months ago, we went to a place in our 50th anniversary and where I used to live when I was a kid in Spain.
I used to climb all these mountains and all these things. I wasn't able to do that this year because of my vision. But I know with this, I'm gonna be able to go there and climb those mountains again because it's been amazing. It's been amazing. And I know Dr. Neena and everybody else here are working their butt off to get us better. And I thank them, you know, all of them, for what they're doing for us. Thanks.
Thank you, Manny. That was great story. And great demo. I appreciate it. Adam, please.
Yeah, it's gonna be a bit hard to prepare with that one. I'm sorry. No worries. You can tell he's been here before. My name's Adam Pike. I'm 21. I was diagnosed with Stargardt's when I was around 13. So the experience for me is kind of a bit more blurry as I don't really remember too much from when I was younger and first experiencing it. But one of the most vivid memories I first had with Stargardt's was when I was put in the back of my science class in eighth grade.
That was one of the first times I really noticed that I was kinda struggling to see the board on the other side of the room. After experiencing that, you know, there wasn't any real concerns. It's very typical for kids around that age to get glasses. But the next thing that happened is when I went to my physical, it came back as I really struggled with the eye test, worse than I ever had before. So, of course, there was no alarm bells at this point. It's just, "Oh, I'm gonna have to go get glasses." You know, as a middle schooler, I was pretty upset about that fact. So we ended up going to the ophthalmologist, just a small kind of local one in my home of Rhode Island, and, you know, sat down on the chair.
They pulled up the big glasses thing, put it on my head, and I started doing the eye test. And, you know, they checked my sister's vision. She was in and out in maybe five minutes. And then I sat there for first 10, then 20, then 30. And eventually, I was in that chair for like 45 minutes. There was a lot of kind of skepticism at first. He's like, "Are you just trying to get glasses?" 'Cause, of course, a bunch of kids in middle school would do that. And it was after quite a while that he started to realize, "Oh, there might be something else that's happening here." Puts in the dilation drops, sits me down. I wait the 20 minutes or so, in order for them to kick in.
And then when he sits down, he says, "Oh, you know, we've noticed something at the back of your eye." "My guess would be Stargardt's. There seems to be something on the back of the retina." Of course, I had no clue what a retina was. I was in eighth grade science at the time. So it all kinda went over my head. But then the question was, "Well, what does this exactly mean?" And the answer he told was you could go legally blind in anywhere from 10 to 20 years. So, of course, that news was very heavy to hear at the time, especially with my mother and sister there. It's not something you expect to hear when you just kind of go to get a basic eye checkup.
Then the next question is, "What do we do next?" And, of course, I think this is a very common experience. There was kind of a shrug of the shoulders. You could try going to this person, but there really is no cure. So that was a very heavy drive home. And then, of course, over the next year, it was just a prediction of Stargardt's. So there was kind of holding out this hope, "Oh, it could be something else, something maybe a bit more treatable." And then it was eventually when I went to Dr. Fulton at Boston Children's Hospital my freshman year of high school, that we eventually got the genetic testing done, and it came back as Stargardt's. So that was the kind of start of my journey in, like, figuring out what it was.
And I know the genetic testing at least was allowed kind of me and my family to really accept that this is what I had. And then, of course, the next process, we started looking at clinical trials. And at the time, there weren't really many kind of in the works. And if they were, their funding was getting suspended, or there was a bunch of kinda confusion if they'd even be going on. So, of course, for the going through high school and then into college, it was just kind of every single checkup I would go to, I would see, "Please let my vision be the same. Please let it be the same." You'd kinda sit down, get the results, and it'd get slowly worse and worse and worse, but relatively stable.
So, going through, you know, a lot of my high school years and then into college, I would start to notice things like I was having more trouble reading around just the end of my freshman year of college. I eventually failed my vision test for getting my license renewed. So I had to stop driving. So it's been a very slow battle with time. And, of course, it was around just a bit before this time last year that my family had kinda found, my mother specifically, who kinda kept up a lot with the clinical trials that were happening at the time, heard of the Ocugen trial. And it was really promising, you know? There was, of course, a huge amount of skepticism going into it. There had been a lot of words about trials in the past that hadn't gone anywhere, especially for Stargardt's.
You know, it's always a worry of, you know, will this actually do anything, or am I committing myself to a clinical trial and kinda barring myself off from something in the future? But after looking more into it, heading down to Arizona, kind of having them explain it to me, it seemed really, really promising, and promising enough to, you know, kind of say, "Okay, we'll do this." Of course, with my vision getting worse and worse over time, the big thought process was, you know, "I have good vision now, but, of course, when is it gonna speed up? When is Stargardt's gonna get worse? You know, I can't drive today. Maybe I won't be able to navigate the streets tomorrow or next year." So that was a really big decision for me. And, of course, I did it parallel to college, flying down to Arizona biweekly.
So that was a bit of strain on my classes. But, yeah, that's kind of been my journey up until this point, and it's led me here. So it's been a very good experience, and I'm very happy to be able to say that I'm in a clinical trial. You know, if you told me that four years ago, I'd been incredibly skeptical. So, yeah, it's been a great experience so far.
Excellent. Thank you. I really wish we had a couple more hours for this panel, but I have another question, that some of you briefly alluded to it. But when you were faced with the prospect of neurotreatment, and there were a few clinical trials, I understand, that you could choose from, what led to your decision to choose Ocugen's trial specifically? You can go in your order.
Sure.
We'll start with you, Adam.
Oh, right back into it. So for me, of course, I'd heard quite a bit about clinical trials. Dr. Fulton was fantastic up in Boston Children's Hospital for kind of always keeping us up to date on what was happening. And we always kind of, or my mother specifically, always kinda followed a lot of the kind of postings to see what was happening. And we did that for eight years. So it was quite a long time, and there were quite a few trials which kinda started up but didn't seem that promising. And I would say the biggest reason for choosing Ocugen is it seemed very promising. There had been a lot of kind of, you know, worry, especially about the gene that's related to Stargardt's, I believe, was too big to supplant into the eye.
So a lot of kinda genetic trials before had really run into some problems. And, of course, the approach seemed very different, which was a huge kind of incentive to be interested in it. And the more I kind of got to know the team, actually see who was working on it, slowly but surely, you know, the confidence in the trial kind of increased more and more. And I would say that's the biggest reason. The kind of new approach was very exciting to see. And then to kinda see the people backing it, really kinda allowed us to put faith in the trial.
Got it. All right. Thank you. And, Manny?
Well, since I've been in, with D r. Lam, who's one of the specialists in retinitis pigmentosa, every time there's a trial, he calls me up, "Manny, we got this and that." So but this one, it was a little bit different. It was, I will say, somehow, the base, the foundation of the study was totally different. It was a one-time surgery. Yes, we had to go through different steps on the study to be able to test it to see how the improvement was going on. But the other part was that I loved it 'cause I had done it in placebo tests, and I didn't like that. When I got this one early, it was no placebo involvement. Yes, we were the first guinea pigs, but at my age, what I got to lose? You know, really. So and I know there's a lot of kids.
I got two kids and then four grandkids. And also find out that I was told that the fifth generation will the illness stop. So that I was the fifth generation, and I find out that that was not true. So that is when I went into this trial with no placebo. It was the real thing. And that was a major decision for me to become part of it. And now you see the results are unbelievable. So it was a no-brainer making the decision.
Got it. Thank you, Mary. Mary?
From the time that I learned I had the macular degeneration, the only thing that was available to me was the PreserVision AREDS 2. And I very faithfully took it, one in the morning, one in the evening. Maybe it should have been helping me, but I sure don't. I never saw any difference at all. I kept progressing. So, I'd look on the internet. I'd see if there was anything out there. I would look up the Macular Degeneration Society to just see if there was anything on the internet about it. You didn't really see anything.
The only two things that I had seen, and possibly that's what I learned from Dr. Angela, was there were two injections in the eye. You got them about monthly or what, every other month. And they could cause the wet macular degeneration. You don't want that. They had other problems. So when the gene therapy was presented to me, I looked up gene and was like, "Ooh, wow, this is something." But I noticed that there were a lot of gene therapies going on. Not the, not the eyes.
No, I'm talking about just different parts of the body. And this has been going on for a long time, and I didn't realize that. Well, if you've been doing gene therapy for a long time and now we're doing it on the eyes, I figured, "Hey, this is probably gonna be safe." And everything I saw was very positive. Dr. Shah and his whole team just made it very positive. And I was very excited to be a part of this group. So that's my story.
Excellent. Thank you. Thank you.
Yeah. So I echo all the other patients up here. I think that the promising nature of the gene therapy was definitely the reason I went with this, with this trial. There were other trials offered to me, like I mentioned previously, that had some safety. There were some safety things that could have gone on with high vitamin A. So I think definitely the one injection as well, just one injection and done, was very enticing to me as well. And, like Mary, I did a lot of research on gene therapy. And having some scientists in our lives, we were really told to go the gene therapy route, and see what it could do. So, yeah.
Got it. Excellent. Do we have time for an audience question or? Yeah. Yep. Does anyone in the audience have any questions?
Yes, please. Yeah.
Wait, wait, wait, wait, wait.
I'm a little interested about the treatment itself and what it was like to be treated, the actual process, how long did it take, the amount of pain, the recovery, any side effects, or anything about that you would note that you would discuss with others who are potential patients in the clinical trial or after approval. Would you think this is something that's going to be widely used, or is it more of an experimental, yet-to-be-refined type of treatment? I'm dying to do it on my other eyes.
Okay. Thank you. That's a good answer. We all are. It's no pain. The people at the hospital are wonderful, and I mean, I will do it again. Mm-hmm.
How long did it take, Manny?
What do you mean?
The actual operation.
Hour and a half, probably. Within, you know, you have to wait there for a little bit for the anesthesia to go away. I had light headed after that, but the following day, you had to go back to the clinic. After that, it was gone. You had to put some drops every so often. And I didn't really had any. Sometimes I forget that I had the operation. So it was literally less than half an hour. Just removing some fluid and putting some fluid in. Yeah.
It's a day there in the hospital? I mean, for two days?
No, no. It's an outpatient. What we did, because we live a little far and traffic, and horrifying on traffic with an accident, so we stay at a hotel close to it. So we got in there, and they put you a patch so you don't hurt your eye. And they check it out and go home. No problem.
You go home the second day?
Yeah. No, the first day you go home. No, no, no. You could go. Yes. Yes. We, after that, we had a protocol that we go by every. I can't remember now. We went many times. Right. But it was like the procedure before the operation, the surgery. We had two days testing. We had the Oculus. We had the Octopus. I mean, two full days of testing. Okay. And after the surgery, I don't remember, a month or two months, we had to go back and do the same all over again. The testing. The testing. Two days.
Two days, probably like 4x after that. Then 4x , like every three months. Every three months and six months. We just did December, I think. We did the two years. For two years? Two years. Now, I don't know. I would just say, yeah. I don't know what's the next, the next step is.
I would just say I feel like it would be a very easy treatment for people moving forward because it was a very low-time commitment surgery. It wasn't you weren't fully put to sleep. It was a twilighted surgery. You were up and awake and feeling fine within hours. There was no I felt no pain in the eye. I felt nothing like that. It was a very quick surgery.
So the next day, you got followed up on at the clinic, and then you went home from there, and just followed up with three drops a day and then a steroid regimen for a while. Then that was that. They still follow up, obviously, but the treatment was very, very easy.
Mine was about an hour operation. I could hear everything that was going on. They were very professional. Very. They did a great job. But yes, you take steroids. We took the Prednisone, the pill. I think there were six weeks of it with decreasing doses. After the surgery, I don't remember. It could have been for a day, two or three. I think it depended upon how things were going because I was checked the next day.
But I had to sit like this a lot. And that was to help that healing process and what was going on inside my eye from the surgery. That wasn't real fun, but after I did that a few times, it wasn't too bad. And I had a little foam thing to rest my head on. And then, yes, we had eye drops. Three different eye drops that lasted for it could have been up to about four weeks. I'm not sure. And I think some ended a little earlier than others. Yep. You definitely wanna follow, though, what they want you to do. So that would be very important if somebody wants to cheat on that follow-up. But no, she's right. No pain. The procedure went without any event. I was out of there the same day. No overnight stays and nothing like that.
Where did you get your surgery?
Where I got mine? At Dr. Shah did it in La Crosse, Wisconsin, at Gundersen Clinic.
How about you, Manny?
I did at Bascom Palmer. Oh, Bascom Palmer. Yes. Yes.
Does everybody do the head-down thing?
Did you do that, Manny, with the head down?
What do you mean?
After the surgery?
No. No. No. No.
Dr. Shah, I'd have to explain that. I don't totally understand the exact reason for it. Yeah. Yeah. I had the yeah.
So why don't we just pause for a second, ask each of our surgeons to give a little bit more on their experience with the surgical outcomes. Lejla, do you wanna start?
Yeah. Sure. No. I, I'd love to first of all thank you so much for sharing all of your stories. It's just so touching to hear it. Somebody who's been taking care of patients and not having treatment options to hear some early changes and kind of just positive outlook on a clinical trial is really exciting. Gene therapy, the only approved therapy currently is Luxturna.
It's delivered exactly the same way as this therapy as well. It's a surgical intervention where the patient is taken for outpatient procedure. The surgery itself is a routine procedure that we do essentially for any retinal type of problem that needs surgical intervention. It involves us removing the gel inside the eye and then going in the back part of it and delivering the virus, the viral vector that carries the modified gene. The surgery itself is, as mentioned, outpatient. So patient does go home after that.
The positioning that was mentioned is typically not involved, but there may be some concerns in terms of retinal tearing or some findings that were found at the time of the procedure that would warrant that additional step. Typically, we do not anticipate positioning to be part of the procedure afterwards. Then there are post-op drops as well as prednisone that you mentioned that's taken to decrease the chance of infection and inflammation. Now, it is a surgical intervention, but as we mentioned, it is something that we routinely, as a retina specialist, do for all our patients requiring retina surgery. Because it's one-time delivery, I think that is the part that's exciting for me as a specialist to offer this. We are, you know, doing this one time with hopes that this is gonna be a lifelong effect for the patient.
So for me, yes, a surgical option, but one that is potentially one-time and life-changing.
Yeah. And I'll add that, you know, through my career, my goal and my passion has been to treat inherited eye diseases, you know, even since I did a PhD on genetic eye disease. And now, finally, instead of just saying the treatment is coming in five or 10 years, we have something to offer right now. I think that's amazing. And I'm so grateful, you know, to all the subjects, the patients that have been participating. They're really true pioneers for these treatments, you know, coming out to Arizona and, you know, it's nice to see you here again.
But, you know, so it's really, you know, I've seen so many people coming from all over the U.S. to Arizona to see if they are potential candidates. The interest in this study has been huge. I mean, it's hard to describe how many people come in and reach out to us. We get emails, you know, two every day, just, you know, cannot be a subject. They find me on LinkedIn, on Facebook. It's, you know, I don't think you understand the level of demand for treatment for retinitis pigmentosa and Stargardt disease. There are other studies going on, but I think that this is really compelling, you know, the data that I heard today for the first time is really exciting.
And I, you know, we're part of the Stargardt macular degeneration study too. There are options. I, you know, use Syfovre and Izervay. Those are approved drugs that I tell patients, "This is the best we have for now. There will be new drugs that are better coming out soon." So just bear with us. We'll have better drugs coming out really soon. So I think Ocugen really has a great portfolio about, you know, these exciting treatments, you know, for all these diseases.
No, I think I second that. And usually, there's no positioning in Mary, at a special situation in which two to three days, she had to position for a certain time every day. Treatment-wise, you know, as I can see a lot of migrants in the room. I'm a migrant as well. I used to go overseas on vacation 20, 25 years ago. Each time I would go, people would think this is an eye doctor coming from the U.S. at the top-notch place. They would bring kids and adults with blindness, including RP. They would ask me, you know
, "Do you have a treatment you can offer to us?" It was very difficult to tell them that no. Then they would say, "Would you come from America? There must be some treatment over there." Then you have to disappoint them that no, there is no treatment. Many of them, where I'm from, there's consanguineous marriages, and RP is very prevalent for that matter. I did a lot of work in RP as well, and I still do. You know, it was very difficult to give an answer to them.
Geographic atrophy, one, is not as common, but still a bit present as well. At that time, wet macular degeneration was also. There was no treatment for it. Before 2006, there was no treatment for it. I think it's very exciting to see that fast forward 25 years, 24 years, give or take. I think we started in 2015 or at the com this come in 2013, but gene therapy started coming about 2010, but really gotten mainstream attention after that.
The thought of treating someone and then, you know, the second thing you have to understand is, and I would think my colleagues would second it, it is tedious to inject month after month, month after month for macular degeneration patients, especially the wet type, for which we have approved treatment. I'm not talking about how anti-complement works.
The patient's logistics of that coming in, you know, you don't, we don't understand it often, but someone has to take time off to bring them in. So it's not just that person coming, but you also have to understand the logistics which go into bringing them more. So any treatment which reduces that burden on these patients is marvelous. It's great. It's amazing. And also, you have to understand that we are aging population. We're living much longer. And yes, we have a set prevalence of, say, RP and Stargardt disease. We have a finite population of that which grows with the population growth. But aging, a lot more people are living longer and healthier. So macular degeneration and geographic atrophy is going to be a real big challenge as part of our aging process.
If we have to repeat the same cycle of injecting month after month after month for geographic atrophy as we do for wet macular degeneration, I think it's gonna be a big logistical cost and healthcare burden on everybody. Emotional burden too. People have done studies to see how emotionally taxing it is for patients to come every month as well. From my standpoint, I think gene therapy offers that promise that, yes, one treatment, you're done. And I think that's where I am really excited about this whole prospect of the new and upcoming treatments, correct the gene or modify neuroprotection as well. Multiple pathways which are targeted with one single treatment hold a lot of promise.
Question. Would this gene therapy help someone that has already gone blind? So should I take it?
Yeah. One of the things you have to understand is, first, we have to establish why someone has gone blind. The blindness has come from loss of tissue already. Then the definition of blindness is legally blind or completely blind and so on and so forth. Once the tissue is lost, unfortunately, unless you transplant new tissue to grow in its place, it is not possible to recover that vision. However, people who are losing vision, you want to slow it down and make sure the edge of the lesion, as in geographic atrophy and retinitis pigmentosa that reverses itself, comes from outside in. You preserve a neuroprotection or provide protection to the cells which are living. Keep in mind, for example, retinitis pigmentosa, okay, there's only one cell type in the retina which is damaged, either rod cells.
But then the normal cells' cone also start to die, and then after many years of research, we did find out that it is the oxidative stress which actually not only damages more rods which are already abnormal, but also cone cells as well. Because if you had the cone cells intact and you lost all your rods, you would be able to function well in bright lighted conditions, not in dark, but bright light conditions. But why do these cones die? And that's where the whole pathway of multiple things going into damaging the cone. So preserving the retinal tissue is the key. Restoring the tissue is a whole different kind of treatment paradigm.
For retinitis pigmentosa, some patients do report improved vision. I had one patient this last week that told me that he can see better than the lights, and his peripheral vision is improving. So that's the hope that in some patients with RP, we can improve the vision. So slowing down is the promise I tell people, "I can't promise we can improve vision, but we hope to slow it down." But if they have better vision, that's a bonus.
I mean, just to kind of add to that as well. We know that some areas, unfortunately, the cells have completely died, and we know we can't restore those. But some of them are just sick, not quite, you know, dead cells. And we suspect that, you know, gene therapy can help us modify those to not potentially reach the kind of end stage.
So, really help them come out of a sick state to a more healthy state and preserve. I suspect, Manny, what I'm hearing from you is often when we do see retinitis pigmentosa patients, there is preservation sometimes of a little bit of peripheral vision an island. And I, you know, while I'm not your physician, I suspect you probably had some visual field changes early on or at least a little bit an island. And now the therapy has preserved the cells in that area or made them healthier in appearance. And that's why you're starting to see in the corner too. Yeah.
See, this here. Yeah. I wasn't able like here. I can see nothing here. But here, if I have light, more light on the back, I can definitely see it better. That's why when a car goes by now, I can see it. Before this, I will see it here. Now, I have a line here somewhere that it looks like it's coming together. You know, the stretch is a little. I'm not sure. Don't.
But I think nonetheless, I'm very encouraged to hear that. I think when we designed phase I and II of two trials, we're talking about patients who are already losing vision and have lost some of the vision. Unfortunately, we have to start somewhere. It's often, you know, in more of a diseased retinas than we are starting with hopes that we are gonna show safety and to a certain degree of efficacy. And then I hope as we continue to show efficacy, we'll move into treating patients earlier so we can save the vision even earlier, so.
All right. Thank you. Thank you.
I mean, we're gonna move on to the next section just in the interest of time. And the patients will be around as you're grabbing your box lunch, so.
Yeah. Thank you. I wanna thank our patients once again for taking the time to join us for the. Thank you.
I know I have to go into the workforce now, so let me look there. Yes. All right. I'm gonna give a quick commercial update. My name is Mike Shine. I'm the Senior Vice President of Commercial for Ocugen. And I have to tell you, after listening to the panel and hearing our researchers, what a privilege it is to know that I get to commercialize these great therapies. You know, Dr. McCall talked about unmet need and demand.
And what I'd like to do just in three slides is share with you a bit of our perspective on the market for these conditions. So I'm speaking a bit here to the analysts, because at the end of the day, in addition to helping thousands and thousands of patients, we also have to generate a return for our shareholders. So I wanna give you a little bit of perspective how we view these markets. And so what we'll be talking about is the projected landscape of therapeutic agents available on each of these disease states at launch. It is a projection.
Thank goodness for the safe harbor statement at the beginning, but the way we project this is it looks like in RP there may be three therapies approved just ahead of the approval of OCU400, and that's okay. These treatments like Luxturna for RPE65 are very specialized, and that'll treat about 2% of the patients that have RP. Johnson & Johnson's developing a drug for XLRP mutation that may address 5-7% of the patients with RP, then Nanoscope is for severe RP, those that are legally blind. Again, a small percentage of patients will be eligible and get treated with that as we project it, but really what that means is that 260,000 people in the US and Europe, and these projections are just in those two regions, will not have an adequate treatment. They'll have RP.
They don't have a specialized therapy. They don't have a treatment that's been approved. And that's where OCU400 comes in. And you've heard a bunch of stories today. You've seen our clinical data. We're very encouraged that with a broad RP indication, we'll be able to address a significant part of this market. And that means it's a $60 billion market opportunity for Ocugen. When I look at geographic atrophy, it's an even bigger disease. You heard earlier estimates of 2 million- 3 million patients in the U.S. and Europe. We think it's about 2 and a half million patients. And again, we've talked about the complement inhibitors that are approved today with significant limitations in terms of dosing regimen and safety concerns. There's a third that may come to market ahead of OCU410. And a daily, oral retinoid inhibitor may also make it to market.
But again, it looks to us very much like this will be an unsatisfied market. So when we look at untreated or undertreated patients with geographic atrophy, it's an enormous pool of patients that we can help with OCU410. And when there's an enormous pool of patients, that means there's an enormous revenue opportunity as well. And so again, a very important area for us to innovate in and to deliver on our commitments in terms of timing for registration and approval. And Stargardt's a much smaller disease. We estimate about 100,000 patients in the U.S. and Europe. And again, very few treatment options here. Nanoscope for those that are legally blind and then a retinoid inhibitor for early treatment. But we believe again, this market will be largely unsatisfied at the time that we launch OCU410ST.
And so again, potentially 85,000 patients in the US and Europe, a greater than $20 billion opportunity. And I just wanna make one more broad point. And that is when sometimes when people see those numbers, they think, "Wow, you know, how can we afford this drug?" Shankar talked very early on about the importance of Ocugen, our mission to provide access to these therapies to anyone regardless of their socioeconomic status. And what gene therapies allow us to do and the pricing of gene therapies allow us to do is to actually make that happen. Because we have another constituent, our shareholders, that we have a fiduciary responsibility to deliver a return.
So the really neat thing for me as the commercial guy for these programs is we have the opportunity to do both, to get these drugs to people regardless of their socioeconomic status and to provide a very significant return on the investment of our shareholders. It's really, after almost 40 years in the industry, just a remarkable opportunity to help folks that need help and generate the kinds of returns that companies expect from top-tier biotech companies.
And that's my story. Not as compelling as our patient stories, which are absolutely remarkable. I just really, you know, just reiterate the points you've heard earlier today. It really makes it worth getting up and coming to work every morning when we hear the experiences that you folks have and the bravery you have to deal with your disease and to trust us. So we appreciate that. And with that, I'm gonna close the formal presentation part of the meeting. I'll invite Shankar up, and I think we'll have a brief Q&A with the management team.
So Shankar, Huma and Arun, if you wanna head back to the stage for a second. Does anybody have any questions for the Ocugen team? I should ask that as well. I'm gonna just start with Michael real quick, Robert.
Thank you so much. And thank you for the presentation today. So I just wanted to ask with regards to the geographic atrophy data. I know that it's still early stage, but was that functional benefit only observed in the low dose? Do you think this could be mechanistic or just a statistical effect given the small size of the trial?
Who would take this one? Huma? Shankar?
Thanks. Thank you. It's a good question. Let me, again, these modifier genes, what we found out in OCU400 trial before we got the alignment with FDA for phase III, we didn't see any dose response. We believe these modifier genes, you know, if you hit a threshold, you may get good activity. So they have ability to self-regulate. So that's what we have seen in OCU400. That's why agency allowed us to just pick one dose and go to phase III.
So once again, this is preliminary data. We're seeing good data with low dose in both, GA and Stargardt. And so we're hoping, you know, maybe it's already hitting the threshold. Huma, any?
Yes. So actually the data that we have presented, and particularly for six months, that was not only for low dose but also for the medium one as well who were met the, threshold for or the inclusion-exclusion criteria. So those were included. So at this point, it's trending in the right direction. And, we cannot, like, you know, fix that it's at a low dose is effective or medium dose is effective. It's being seen, across all, dose levels at least at this point. And it's six months of data, so.
All right. Thank you. And then just one follow-up for me if you don't mind. Since targeting RORA hits on the four different aspects of the degeneration, do you just have a sense of the degree of complement inhibition that you're seeing for 410 and how that could compare to the purpose-driven complement inhibitors?
Okay. Thank you. Very, very good question. So, so complement, inhibition, is definitely going to be the major driver on the 410 also, including, other pathway. Because if you look at our ABCA4 knockout mice data, one of the key marker for the complement is anti-complement protein CD59. So we do see that in ABCA4 knockout or in macular degeneration condition, this particular protein is significantly suppressed. Actually, in preclinical, hardly we see anything. And when you deliver RORA, we see, you know, upregulation to the normal level. So if you ask me how the OCU400 is going to fare on complement, it is going to do that. But in addition to that, it is going to also take care of other pathway which we talked about.
Well, first, thank you all for all of the presentations that have been really good today. My question has to do with the 410 and the market since if we assume that it's approvable and effective for GA, would the mechanism and the dosing apply to patients who have less severe dry AMD and the other nine or 10 million that would be affected by that? You're talking about intermediate AMD.
Yeah. That's a great question.
Yeah. You know, less severe. They don't have GA. Right. But they do have dry AMD and will progress to GA. Would you treat them earlier before they get to that level and that advanced disease, or would it only be applied for that GA?
I mean, I mean, yeah. It's a great question. And right now, we have to focus on one thing at the late stage. It's easier to diagnose. I think our goal is to go intervene before, but we need to come up with some kind of a diagnostic tool or markers, and I think our goal is to start there, which is the late stage, then go forward, and the projections he presented are five years, right? It's only a five-year model, and it's not, you know, looking at a typically look for 10+, you know, terminal value and all that, but from a patient pool perspective, you're absolutely right. Our goal is not to stop at just the late stage. Once we get this, then we go before, and our goal is to intervene.
Great. Thank you.
All right. I think we'll close the program.
Thank you all for coming. Thank you. Thank you. Yeah. Thanks again to our patients. Really, really appreciate all four of you, Liz, Adam, Mary, and Manny, and our great investigators who spent tireless time. Huma, fantastic job. She's running all our clinical programs, supporting Arun, Mike, everybody else. She doesn't sleep. We have three programs going on. Really, really thankful to all our Ocugen employees. Everybody here, thank you. Thank you for coming to the event today. The presentation is actually posted. It's an 8-K got filed. Tiffany will send you the access.