Ocugen, Inc. (OCGN) Earnings Call Transcript & Summary

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 OCU410ST. And at that point, then we will have our panel. You'll hear from 4 wonderful patients. We have Manny, who is here for our last show case. We also have 2 other patients that have Stargardt disease and 1 patient with AMD. And 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. [Presentation]

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 exciting day today. Our superstars are going to be our patients. And that -- the 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 3 programs we have encompass many blindness diseases. Our hope is in the next 3 to 5 years, forge ahead, get the approvals as expected and if you -- and launch these products and try to help the patients globally. Our mission is not only getting these cutting-edge technology 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 2 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. And 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. So 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 goes across the pharmaceutical industry because we deal with people's lives. Nothing else. And so with that said, again, we are doing well as a public company. We are listed in 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 followed by closing the clinical sections in first half of 2026. We do have orphan drug designations with the FDA and DMA that will give us accelerated path. OCU410 targeting geographic atrophy late stage of dry age-related macular degeneration is going through Phase II. And today, we're going to discuss preliminary efficacy and safety data from Phase I. OCU410ST, 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 2 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 that are going to 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 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. And 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. And I will just -- of course, there's 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. So if you look at overall retinal diseases and especially back of the eye diseases, there's a significant unmet medical need. And if I have to categorize this group of retinal diseases, you can broadly categorize into 2 groups. You have inherited retinal diseases and you're like age-related macro 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 -- all these indications, just retinitis pigmentosa in the U.S. and EU alone affects 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 19 million and if you look at the global prevalence, it is close to 266 million. So there is a significant unmet medical need, and that goes with the Stargardt, which is also like inherited retinal disease and close to 44,000 individuals are impacted in the U.S. alone with this condition. So now what options we have right available? So if you look at currently, 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 impact less than 2% patients in IRD. And for AMD, like if you look at geographic atrophy, we have 2 recently approved product in the U.S., but still there is significant unmet medical need in this space. And there's no product available in the EUA. And the reason for that, what I say because there's a limited treatment benefit and there are some safety and patient compliance, which I'm going to talk about. So when you look at overall, so if you know about this disease and mutations, what is really -- what is preventing us to developing therapy for this indication. So some of the key barriers when you look at to find a therapy for this genetically diverse and multifactorial disease are primarily driven by the high genetic heterogeneity. So what does it mean if you are taking a traditional approach to develop a therapy which are 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 impossible task for any sponsor to take everything from discovery to the approval. Another challenge is that 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. And every individual has its own journey for the disease progression, onset of the disease, progression rate and severity. So there are other factors which are implicated in these 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 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. 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 treatment outcome in terms of benefit and of course, some of the safety challenges that we are seeing with the currently approved product. 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 route. What is really cause for the disease? And is there a way we can address the disease? That is what modified gene therapy does. So if you look at it is -- modifier genes are basically the main control system for how the retinal cells survive and functions 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 the 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 disease, which are nongenetic 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. We are seeing that 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 modality we have right now in the development various company. So if you focus, there are 4 different 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 pros and cons. And here, I want to highlight how they are limited and how we are different, modifier gene therapy is different than all these 4. So if you look at gene augmentation primarily delivers like a normal copy of affected genes, but it is limited to treat only one gene. It is primarily applicable to monogenic condition and recessive condition. Why I'm 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 aggravate the disease. It's not right approach. Gene editing, again, limited by a single gene targeting at the same time. Sometimes it is only single mutation. And sometimes in this patient, one gene can have hundreds of mutation, depending on the location of the base pair. So it's pretty complex. Optogenetics, it is a technology, primarily provides -- 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 there photoreceptor. So it has some potential, but it can primarily target only very small amount of -- sorry, a small number of patients in the later stage. And the cell therapy. Cell therapy is the other approach people are taking in this space. And primarily cell therapy can deliver the sales, but the safety is the biggest challenge and integration of the cells with the retinal and photoreceptors is the biggest challenge in this space. So all this technology, they started their journey long back. And so far we have not seen much success, which really translates to the human and can provide the benefit. So if you look at modifier gene therapy, it is gene agnostic in nature. It targets broader present population. It has potential for a stabilization or reversal of the disease and so far, we have seen very excellent safety and tolerability profile and efficacy in the early stage of clinical development. So how does this modifier gene therapy technology works? So if I have to give you some pictorial representation of what I mentioned about that it does target multiple pathway and does the resetting. So here, you can see that when we delivered the modifier gene to these retinal cells, it targets multiple pathway like photoreceptor development, cone cell development, phototransduction, resetting the molecular network, cell survival. And once you fix this pathway that lead to the survival of retinal cell, which eventually helps with your preserving vision or improving vision in these patients. And in our like preclinical proof of concept study, we have seen this gene agnostic and benefit in multiple animal model. And this slide primarily highlights that whatever structural and functional parameter we looked at in all these 5 different animal models, OCU400 was able to preserve the retinal cells, improve the retinal cell function and also improve some biomarkers in the retinal cell, which are indicative of retina health and function. And at the same time, we also looked at the biomarker, which clearly demonstrate the molecular resetting mechanism of the modifier gene therapy technology. So with that, I'll transition into our another modified gene therapy candidate that is OCU410 based on the RORA modifier gene. So RORA is also a nuclear hormone receptor, it is modifier gene. And what it does 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. And this is some of our proof-of-concept data in the animal model as well as in Vitro model. And as you can see on this slide, OCU410 molecule basically has an entire drusen activity. So 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 a protection of the retinal cell survival under oxidative stress condition and it was able to basically upregulate the entire complement protein. And why it's important? Because complement drives the degeneration of photoreceptor. So if you can prevent the the complement complex formation, then survival of the retinal cells can be improved. So with that, what I would like to highlight here that OCU410, it has a multifactorial target. It targets all these 4 pathways, which are linked to the disease pathophysiology of the AMD. And also, it is a potential onetime therapy. So if you look at currently approved product, you have to like -- a patient has to get either 6 to 12 injection per year. Not only that, there are some safety concern related to induction of CNV. And also, they have a very limited effect. The effect is very much minimized to the structural benefit, slowing the progression of disease like marginally. However, OCU410 has a potential to not only just provide a structural benefit but also provide some 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 later-stage assets in the GA or approved product, you can see here that most of these products, they target only one pathway, whereas OCU400 target all the pathway, 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 digit pathophysiology, though they have the different basis for disease induction. One is age-related, one is genetic disorder caused by mutation in ABCA4 gene, so all the proof of concept animal data is coming from the ABCA4 mice model. So it is basically direct translation from animal model to the Stargardt patient model. And that's why we are also doing the clinical study in the Stargardt patient. Currently, we have completed Phase 1, as Shankar mentioned, and we are going to have interaction with regulatory agency to work on our plan to develop a clinical design, which can be potentially used for the approval of product in the U.S. So 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. And it's kind of like an emotional day for me too, because when you are overseeing a program, you're looking at the data finally coming out, and that's exactly we are interacting with the patients and everything that you do has a meaning as a potential way of addressing the unmet medical needs of the patient. So I'm 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? 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 III novel modifier gene therapy clinical trial, which has a broader retinitis pigmentosa indication. What does it mean 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 III 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 as well 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 a 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 our protocol and up to 5 centers in Canada that we will be recruiting so almost 15 centers in the North America. So in terms of our 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 2 approved products which required a lot of compliance, 6 to 12 injections, Arun has very well presented in the last few slides. But if you look at that dry AMD effects nearly 19 people -- 19 million people in the U.S. and Europe and let alone geographic atrophy affects 2 million to 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 I. 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 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, this OCU410 Stargardt, we have 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 OCU410ST as well. And currently, we will be looking at the Phase II portion of the study where we are actually looking to have the concurrence with FDA for a confirmatory trial for final approval as well. And 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 investigation product, OCU410 GA and ST and also 400, we are now in the Phase III 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. And 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 equity. That's the vision chart that you see in the optometrist's office. For pediatric patients at 9 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 9 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 9 months and 12 months' time point. And in terms of our OCU410 and for GA, as I have mentioned, that we are on track for our completion for Phase II as well, and the safety and tolerability profile has been excellent. Not only that, it's a onetime 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's low GA lesion growth in treated eyes versus untreated eyes at 6 month. And not only that, the low dose demonstrate treatment benefit in by stabilization of visual function LLVA at 6 months. That is a very important point to consider because currently, the approved products have not demonstrated the visual function -- didn't get the approval on that. They got 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 as 6 month and visual function, 60% at of the BCV at 6 months as well. So these are all the updates from the clinical trial updates. 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 and coming from Arizona. It's a little cooler here than back in the desert. And I'm originally from Sweden, if you detect an accent. So I'm going to talk to you about -- previously released data from the CEP290 part of the OCU400 treatment. So as you know, the Phase II study included 80 patients with retinitis pigmentosa and 2 patients with Leber congenital amaurosis. So 2 adults to pediatric patients. And the goal of the treatment was to evaluate the safety and efficacy in OCU400 in this cohort Leber congenital amaurosis, and yes, mutational CEP290 gene. And the reason this gene was selected was based on the preclinical data from the animal studies. So yes, so as we heard, OCU400 is an novel modifier gene therapy and has solid preclinical data from the retinitis pigmentosa, cohort, so very similar. The gene was delivered with subretinal delivery, onetime treatment. The dose that was selected was the medium dose to overexpress the protein NR2E3. And then that's kind of the -- how Phase I/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 value the safety outcomes in these 4 subjects. So we have in a month 9 data efficacy that's going to be presented for all the subjects. We only have the month 12 data for 1 subject who is an adult patient. One subject adult developed complication not related to product, but develop retinal detachment that cost loss of vision. We can't really include all the data from that eye because of the retina detachment. And then 1 patient pediatric -- after 9 months or so, developed high pressure, also developed glaucoma, which is a condition that's related to pressure. So we only have data up to 9 months for that patient. After that, we can't really include it. We think that the reason glaucoma was because of [ Stargardt ] not because of the product itself. So yes, so the outcomes present here will be the best corrected visual acuity, the nationalized youth visual quality -- visual quality of life questionnaire, full-field stimulus threshold testing, which is kind of a dark adaptation test and build the test, and that mobile test was the same that was used for the gene therapy that you've heard about before, Luxturna, that's a similar kind of mace walking around in different levels of lights. So the data that I present here, so if you look on the left panel, you can see that change in the visual acuity, only the one of the outpatient could -- because this is a patient with very poor vision. So only the adult patient, it could be the ETDRS chart. So those are the regular eye chart that you see in an eye clinic. So the solid blue line is the treated eye and the dotted line is the untreated eye. So you can see that over time the treated eye improved and then decreases down back to baseline. However, the dotted line shows a reduction in the visual acuity below 5 letters, which is a threshold cutoff. And we know that these conditions are slowly progressive. So there is progression of the vision change over time in an untreated eye. And looking at the right panel, that's the pediatric subjects, they could not see the ETDRS lines, so we have to use Berkeley Rudimentary Vision Test at a lower level of scale. And for the patient 1, the pediatric patient 1, there's really no change in either eye over this course. So really kind of stable. And in this graph, going up is worse vision. So the treated eye initially had reduced vision, but then at month 9 came back to baseline and the untreated eye for patient 2, the pediatric group again, month 6 was stable, but then at month 9, it deteriorated. So in summary, 2 out of 3 patients that we present here of these signs, they have stabilization or preservation of the vision function on these visual acuity tests. And then going on to the next slide. So here we're talking about this test, this is 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 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, looking at the bars, the improvement is better. So these are different kinds of stimuli that's presented for a dark adaptation. So dark adapted, white, blue or red light. So you can see that the treated eye in the blue bars is minus 1.3%. So improvement detecting red light. That means that the cone for receptor, they can see red, rods cannot see red. So the cone photoreceptor function improved somewhat. It didn't really reach that threshold for the red stimulus. And look, we only have data for 1 pediatric patient because the second pediatric patient has a poor vision because of nystagmus who couldn't perform the test reliably. But this one pediatric patient had also had improved dark adapted red stimulus, much better than the adult, the visual threshold even for the blue stimulus which improvise the rods. So there is some improvement. So both these patients show stabilization, improvement over cone response function. And the cone, as we know, are important for daytime vision, color vision. But still this is a very severe disease to begin with. But if you can improve the cone function, that's very positive. Going on. So kind of summarize here. So as I mentioned before, OCU400 is generally safe and well tolerated in these LCA subjects. You didn't find any severe adverse events related to the study drive. As I mentioned, there was a retinal detachment, we think that's because of the surgery. One patient developed glaucoma, but that was most likely due to steroid treatment after 9 months or so. And then what's positive is 1 without LCA patients showed 1 Lux level improvement in build test, reaching from that level sort of the 130 lux to 50 lux at 12 months. We also saw stabilization of the visual acuity improvement in overall response, with cone response at 12 months and then you have some rising 6%, 7% of these patients or 2 out of 3 had stabilization and preservation of visual function and the visual acuity. Yes, overall, it's the demonstration of the cone function, as I mentioned. And the MAA visual function for this work, the one adult patient had improvement. The second adult patient, even though he had retinal detachment, he reported improvement, but you have to take that with a grain of salt because we can't really take those results into consideration as an attachment and surgeries. Yes. So that's kind of pretty much concludes my part of this afternoon. I'm happy to answer more questions later on.

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-La Crosse, Wisconsin. He will be discussing the updates from our ArMaDa Phase I/II trial. Thank you.

Thank you, Dr. Qamar, and I want to give special thanks to all the patients whose participation in these trials make 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 is part of the trial. I'll start from here. So we all of us know already what geographic atrophy is. We talked about it, we know the burden of that, globally, not just in U.S. everywhere else. So I'm going to 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 3 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 trial. 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 being followed right now in the Phase II dose expansion in which you have a medium and high dose being tried against control group. This will give us a firsthand on head-to-head comparison of treated versus untreated eyes. And these are just some of the primary end points. Of course, safety is paramounting and primary end points are all related 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 luminous vision as well as microperimetry and [ rosen ] volume, which is a structural test. But one thing that Dr. Qamar also mentioned over here is that -- one more thing I want to add that CNV in the fellow eye did not -- 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 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, which is subretinal injection granted, our optic neuropathy, which is reported in other treatments, vasculitis, endophthalmitis for choroidal neovascular membrane in the beginning of the patients that we have enrolled. So the next thing I want to highlight over here is that treated versus untreated and natural history study. You can see that at 6 months now granted at 3 months that we have about 3 patients. And at 6 months, we have -- 3 months, we have 5 patients. And at 6 months, we have 3 patients because that's the data we had available for all the patients who had completed the 6 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 anticomplement treatments already available in the market. And you can see that the slope of the untreated eye over last 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 I wanted to see was a quick look at the publicly available data for the Syfovre or the new treatment, which is anticomplement, every other month treatment at 6 months and every month treatment at 6 months. This shows the difference between the GA lesion treated and untreated eyes, right? So this means this much more tissue was preserved in their treated eyes. So 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 3 months, it is almost equal to the PEOM, every other month treatment of 6 months. So at 3 months, the drug was able to demonstrate in the patients we are tested, that is equal to the PEOM or every other month treatment. And if you look at the 6 months data, it beat both the 3 months, 6 months, every other month as well as the per month. So 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 6 months more than both the PEOM as well as -- so it clearly shows that there is a difference at 6 months when it's compared to the anticomplement available in the market. Second thing, we also looked at the low luminous visual function. Visual function has become very important because end of the day, it is a functioning of the patient, as you may also recall in retinitis pigmentosa we have a MACE in which the patients are tested, how well they do in low luminous conditions, daily activities like walking and going through obstacles. And the same concept applies in geographic atrophy in which we use lower luminance visual function of visual acuity for the patients. And we had shown that there was stability at 6 months among all the patients who were treated with OCU410 and 100% of them, all 3 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 worse anticomplement has shown in published data over 2 or 3 years. This is a 6-month finding. And then all of 100% of patients had stabilization of visual function. And the single injection -- keep in mind, this is just 1 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 preserves more of the RPE cells and on top of the 410 receptor 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. I have to like go through all of this. Director, Duke Surgical Vitreoretinal Fellowship Program, 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 as, she is the 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, Huma. That was very kind of you, I appreciate that. Super excited to be here as well with all of you. First of all, it's exciting to hear the first of our updates and all of the programs that Ocugen is leading. And it's exciting to have options -- a onetime 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 I've made -- it has made so far. I'm going to cover for you OCU410ST Phase I/II study. And just like the other ones who are covering the Phase I/II, well, Phase I data, it is a dose-escalating trial, and we are doing a preliminary time points here with low dose and medium dose and each dose enrolled 3 patients before proceeding to the next level. All of that was approved by DSMB before initiation. And currently, we are sharing with you the available time points, which is for low dose and reduced dose. So we're focusing on 6 patients all throughout. I do want to point out the primary endpoint is like other safety trials. Our Phase I trial is safety, so we want to ensure we address those and talk about those. And then secondary endpoints that we want to see efficacy as well efficacy in terms of acuity, but also other changes, especially on OCT. The key inclusion, exclusion criteria are typical of any inherited retinal disease. We want to 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 on 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 -- 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 6-month data for the low dose, 2 patients in that group and medium dose 1 patient data point available. It's exciting to see that the growth of atrophic areas significantly different at a slower rate compared to treatment in untreated and that difference is 84%. So 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 are 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 where more and more talk about preservation of tissue and decreasing yes, growth of that atrophic area, but really pursuing retinal function which will lead to visual function as well. So 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 improve. So what are the numbers like? The atrophic lesion growth has decreased, as I showed to you, 84% between treated and untreated eye. 4 out of 5 or 80% of treated eye demonstrated preservation of macular volume on OCT readings and 3 out of 5 or 60% or so treated eyes demonstrated preservation retinal thickness overall. This is leading to visual function improvement in about 3 out of the 5 patients we are sharing with you today has that 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. And we do show that there is stabilization to improvement in visual function, retinal outcomes and is exciting to kind of surge forward to the Phase II and will share with you, there's going to be FDA discussion to further use that trial as a complimentary trial in the future. 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. So the stage crew is going to put the next scene up here. And I'm going to introduce our analysts from Chardan, Dr. Daniil Gataulin. He's a senior research analyst of Biotechnology, and we'll have each of our patients start to come up to the stage, please.

Great. Thank you, everyone. Thank you Tiffany and thank you, Ocugen for giving 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're 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 want to 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 notice the changes in your vision, the doctor appointments that you went through, and the moment you receive the diagnosis and what that meant for you? We'll start here.

My name is Liz. I have Stargardt disease. I went to several eye doctors growing up for contact and regular glasses appointments. And so around the year 2013, they started to notice drusens on my retina and asked me to follow up with an ophthalmologist. So I went for several appointments over the last 8 to 9 years to ophthalmologists, different ones, and they just kept monitoring the status of my retina. And they said no changes, no changes, everything is good. And then at the beginning of 2023, I noticed that my vision was declining significantly. And so I went to get another opinion at an ophthalmologist where they did -- Wills Eye Hospital in Philadelphia ended up doing genetic testing after I ask them, it could potentially be Stargardt and I've heard that before. So could we take a look at that. So they did a genetic test on me, and it came back Stargardt. And from there, I didn't know of my options. I was told that it had -- there are no treatments out there for me. For someone with my condition, there's nothing approved for me. So having 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, on all the information available to a patient like me. And 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. And that made me feel as a patient very safe and very comfortable to move forward and with gene therapy being so promising, I thought that was the best way to go. So from 2013 to when they first started to notice something in my eyes until now, I think it was big progress for me.

My name is Mary Marcel. 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 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 Angela Darveaux. 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 a 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. And I looked it up on the Internet, and I want to know everything I could about Ocugen 410 so that I could be informed and talk with him and just know what I was talking about and everything. So when I saw Dr. Shah, I'm at the -- physical requirements that you need to have in my eye was in the condition that you needed to have for everything else. And he was going to explain it to me. And he did do some really good explanations as far as just what it's all about. But I did tell him that I have looked up the Ocugen 410 and I know a lot about it. And yes, I'm very interested in being a part of this study. Well, they did not have the applications ready yet, but he says, well, when we have applications we'll get one to you. And from that moment on, I felt pretty confident that they would accept me and was certainly hoping they would accept me. And yes, I was accepted for the Ocugen 410 trial. And my first -- 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 5 to 10 years ago. But I was looking at the sky at night, and we had a place in the country, and so you could see all the sky. And I saw stars, but when I wanted to look directly up at the stars, there was a great cloud and there were no stars. And it's like, well, I'm sure I saw stars up there. And sure enough, yes, 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 got to 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, 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.

Well, thank you. I thank all of you for being here. Interesting to hear 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 grandparent, my grandfather, my uncles, my aunt, they all had the disease. And 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. Then that was back in Cuba. I went to the best doctors in Cuba. There was no cure. I came, I begin to study or being going to the -- be patient at Bascom Palmer, which is top-of-the-line hospital for the eyes. And I've been in 2 other studies before this one, and they canceled 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 2 years ago, somebody calls from the hospital asking if I want to be in another study. So when we start talking, I start to beginning to like what I was hearing the way they 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. It took 40 -- it took 20 years when I was 40, 43, my eyes started getting the [ empty pigments ] in it. So I had no problem driving that. I have no problem doing anything. But as my age started going, I started seeing declining on my eyesight. So that's when I start getting worried. Well, this study today, I can only see through 2 channels. Everything else is blind. Can I do the -- what I. Okay. Everybody has a piece of paper there. I want to do something because that's the best way I can do it. If anybody was here February -- last February? Good. I want you to draw an eye on this corner, please. everybody. This is OCU101. And I want you to draw a hole into your eyes. 2 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. You can see me, right? Thank you, Hani. Now that's my vision. But today -- and I never told the company about it, I want you to on the second draw another eye and do the same. But this time, fold it and put it next to you like this. And I don't know -- well, it's going to take too long, but I can see through this side now, I still drive a car right around the neighborhood. And in February, I could see this here, 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, not good, I don't know what it is. And I thank the company for doing this to us. It's giving us -- I'm 70 years old. I love -- we love to travel. And this year, well, 2 months ago, we went to a place in our 50th anniversary and where I used to live when I was a kid in Spain, and I used to climb all these mountains and all these things. And I wasn't able to do that this year because of my vision. And -- but I know with this, I'm going to be able to go there and climb those mountains again because 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, all of them for what they're doing for us. Thanks.

Thank you, Manny. That was great story and a great demo. I appreciate it. Evan, please.

Yes, it's going to be a bit hard -- I'm sorry -- I can tell he's been here before. My name is Evan Pike. I'm 21. I was diagnosed with Stargardt when I was around 13. So the experience for me is kind of a bit more blurry. I don't really remember too much from when I was younger and first experiencing it. But one of the most visit memories I first had with Stargardt was when I would put in the back of my science class in 8th grade. And that was one of the first times I really noticed that I was kind of struggling to see the board on the other side of the room. And after experiencing that, 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 is 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 going to have to go get glasses. As a middle schooler, I was pretty upset about that fact. So we ended up going to ophthalmologist, just a small kind of local one in my home of Rhode Island and 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 they checked my sister's vision. She was in and out in maybe 5 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 because, 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 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, we've noticed something at the back of your eye." My guess would be Stargardts as there seems to be something on the back of the retina. Of course, I didn't include what a retina was. That was in 8th grade science at the time. So it all kind of went over my head, but then the question was, well, what does this exactly mean? And the answer next 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 it was mother and sister there. It's not something you expect to hear when you just kind of go to get a basic eye check up. And then the next question is what do we do next? And of course, I think this is a very common experience. There's kind of 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. So there was kind of holding out this hope, Oh, it could be something else, something may be a bit more treatable. And then it was eventually when I went to Dr. Fulton at Boston Children's Hospital and my freshman year of high school, that we eventually got the genetic testing done and it came back as Stargardts. So that was the kind of start of my journey and like figuring out what it was. And I know the genetic testing at least was allowed kind of me and my family to 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 kind of confusion if they'd be going on. So of course, going through high school and then into college, it was just kind of every single check up, I would go to, I would see, please let my vision the same, please let it be the same. You kind of sit down, get the results and it gets slowly worse and worse and worse, but relatively stable. So going through a lot of my high school years and then into college, I would start to notice things like I was having trouble reading around just the end of my freshmen college, I eventually failed my vision test for getting my license renewed. So I stopped driving. So it's been a very slow battle with time. And it was around just a bit before this time last year that my family kind of found, my mother specifically, who kind of kept up a lot with the clinical trials that are happening at the time. I heard of the Ocugen trial and it was really promising. There's, of course, a huge amount of skepticism going into it. There have been a lot of words about trials in the past that hadn't gone anywhere, especially for Stargardts. It's always a worry of, will this actually do anything or am I committing myself to a clinical trial and kind of barring myself off from something in the future. But after looking into it, heading down to Arizona kind of have them explain it to me, it seemed really, really promising and promising enough to kind of say, okay, we'll do this, of course, with my vision getting worse and worse over time. The big thought process was I have good vision now, but of course, when is it going to speed up? When is Stargardt is going to get worse? 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 yes, 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. If you told me that 4 years ago, I've been incredibly skeptical. So yes, it's been a great experience so far.

Excellent. Couple more hours sort of 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 no treatment and there were a few clinical trial I understand that you could choose from. What led to your decision to choose Ocugen's trial specifically?

So, for Mike Rose, of course, I've heard quite a bit about clinical trials. Dr. Fulton was fantastic up in Boston Children's Hospital for kind of always keeping us up today on what was happening. And we always kind of, my mother, specifically, always kind of followed a lot of the kind of posting to us what was happening. And we did that for 8 years. So it was quite a long time, and there are quite a few trials which kind of started up, but didn't seem that promising. I would say the biggest reason for choosing Ocugen is, it seems very promising. There's been a lot of kind of worry, especially about the gene that's related to Stargardt. I believe it was stupid [indiscernible] into the eye. So a lot of genetic trials before I'd really run into some problems. And of course, the approach seems very different, which was a huge kind of incentive to be interested in. And the more I kind of got to know the team actually see he was working on it. So 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 kind of see the people backing it really kind of allowed us to put faith in the trial.

Manny?

All right. Thank you. Well, since I've been with Dr. Lam, which is one of the specialists in retinitis pigmentosa. Every time there's a trial, he calls me up, Manny, we got this and that. But this one, it was a little bit different. It was, I would say, somehow the base, the foundation of the study was totally different. It was a onetime surgery. And yes, we have 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 because I had done it in placebo test and I didn't like that. When I got this on early, it was not placebo involved. Yes, we were the first guinea pigs, but my age, what I got to lose 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 I was the fifth generation. And I find out that was not true. So that is when I went into this trial with no placebo. It was the real thing. And thus, that was a major decision for me to become part of it. Now you see the results are unbelievable. So it was a no-brainer making the decision.

Mary?

From the time that I learned, I had the macular degeneration. The only thing that was available to me was the preservation [indiscernible] 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 looked 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 2 things that I had seen and possibly that's what I learned from Dr. Angela was there were 2 injections in the eye. You got them about monthly or 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, oh, wow, this is something. But I noticed that there were a lot of gene therapies going on. Not the eyes now. 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 going to 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.

Yes. So I echo all the other patients up here. I think it's the promising nature of the gene therapy was definitely the reason I went with this trial. There were other trials offered to me, like I mentioned previously that had some safety. There were some safety things 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 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.

Do we have time for an audience question? Anyone in the audience have any questions? Yes, please?

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, that you would not 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 eye.

Okay. Thank you. That's a good answer.

There is no pain. The people at the hospital are wonderful. And I mean I will do it again.

How long does it take, Manny?

What do you mean?

The actual operation?

1.5 hours, probably within -- you have to wait there for a little bit to [ anesthesian ] to go away. I had a lightheaded after. But the following day, you had to go back to the clinic. And after that, it was gone. You have to put some drops every so often. And I didn't really had any -- sometimes I forget that I had the operation.

Do you stay there in a hospital for 2 days?

No, no. It's an outpatient. What we did because we live a little far on traffic and -- horrifying on traffic with an accident. So we stayed at our hotel close to it. So we got in there. And would they put you a patch, so you don't hurt your eye. And they check it out and go home, no problem.

Go home the second day?

Yes. No, you could go -- Yes. Yes. We -- after that, we had a protocol that we go by every -- I cannot remember now -- we go in many times. But it was like the proceed. Before the operation, the surgery, we had 2 days testing. We had the [indiscernible]. We had [indiscernible]. I mean, 2 full days of testing. And after the surgery remember a month or 2 months, we had to go back and do the same all over again, the testing, 2 days. And 2 days, it's probably like 4x after that. And then every 3 months and 6 months, and we just did December, I think. We did that 2 years. 2 years. And now, I don't know -- I don't know what 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 was that you weren't fully put to sleep. It was twilight surgery. You were up and awake and feeling fine within hours. And there was no -- I felt no pain in the eye. I felt nothing like that. It was a very quick surgery. And so the next day you got followed up on the -- at the clinic and then you went home from there. And just followed up with 3 drops a day and then a steroid regimen for a while. And then that was that. So -- and they still follow up, obviously, but the treatment was very, very easy.

And mine was about an hour operation. I could hear everything that was going on. And they were very professional, very. But yes, you take steroids. We took the prednisolone , a pill. I think there were 6 weeks of it with decreasing doses after the surgery, I don't remember, it was for -- it could have been for a day, 2 or 3. I think dependent 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, 3 different eye drops that lasted for -- that could have been up to about 4 weeks. I'm not sure. And I think some ended a little earlier than others. You definitely want to follow them 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 there the same day, no overnight stay and nothing like that.

Where did you get your surgery?

Where I got mine? Dr. Shah did it in La Crosse, Wisconsin at Gundersen Clinic.

How about you, Manny?

I did that at Bascom Palmer.

Does everybody do the head down thing?

What do you mean? No. No. No.

Dr. Shah have to explain that. I don't totally understand the exact reason for it, I have the...

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 want to start?

Yes. No. First of all, thank you so much for sharing all of your stories. It's just so touching to hear it and 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 your 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. The patient does go home after that. And the positioning that was mentioned is typically not involved, but there may be some concerns in terms of retinal tearing or some findings that was found at the time of procedure that would warrant that additional step. But typically, we do not anticipate positioning to be part of the afterwards. And then there are post-op drops as well as Prednisolone and you mentioned it's taken to decrease the chance of infection inflammation. Now it is a surgical intervention. But as we mentioned, it is something that we will routinely as a retina specialists do for all our patients requiring retina surgery. And because it's onetime delivery, I think that is the part that's exciting for me as a specialist to offer this, we are doing this one time with hopes that this is going to be a lifelong effect for the patient. So for me, yes, a surgical option, but one that is potentially onetime and lifechanging.

Yes. And I'll add that through my career, my goal and my passion has been to treat inherited eye diseases. Even since I did a PhD in a genetic eye disease. And now finally, instead of just saying the treatment is coming in 5 or 10 years, we have something to offer right now. I think that's amazing. And I'm so grateful to all the subjects that the patients have been participating. They're really true pioneers for these treatments coming out to Arizona, and it's nice to see two of you here again. But -- so it's really -- 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 e-mails 2 every day, just can be subject, the find me on LinkedIn, on Facebook. It's -- I don't think you understand the level of demand for treatment for retinitis pigmentosa there is. And Stargardt disease, there are other studies going on, but I think that this is a really compelling the data that I heard today for the first time, it is really exciting. And we're part of the Mac degeneration study too. There are options. I use [indiscernible], 2 drugs that 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 will have better drugs coming out soon. So I think Ocugen really has a great portfolio about these exciting treatments in these diseases.

No, I think I second that. Usually, there's no positioning, Maria, a special situation in which 2 to 3 days, she had to position for a certain time every day. Treatment-wise, as I can see, a lot of migrants in the room. I am migrant myself and I used to go see the vacation 20, 25 years ago. And each time I would go, people would think this is an eye doctor coming from the U.S., he's at a top-notch place. And they will bring kids and adults with blindness, including RP. And they would ask me, do you have a treatment you can offer to us. And it was very difficult to tell them that, no. And then they would say, would you have come from America, there must be some treatment over there. And then you have to disappoint them that no there is no treatment. And many of them, where I'm from, there's consanguine marriages and RP is very prevalent for that matter, and I did a lot of work in RP as well and still do. And it was very difficult to give an answer to them. Geographic atrophy is not common but still present as well. At that time, wet mac degeneration was also -- there was no treatment for it. And before 2006, there was no treatment for it. And I think it's very exciting to see the fast forward 25 years, 24 years, give or take. I think we started in 2015 or at the -- this company in 2013, but gene therapy started coming about 2010 later, before that, but really mainstream attention after that. And the thought of treating someone. And then 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 macro degeneration patients, especially the wet type, which we have a pretreatment, I'm not talking about how anticomplement works. The patients, logistics of that coming in, 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 bring them over. So any treatment, which reduces that burden on the these patient. It 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 the aging process. And if we had 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 going to be a big logistical cost and health care burden on everybody. Emotional burden to people have done studies to see how emotionally taxing it is for patients to come every month as well. So 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 treatment. Correct the gene or modify the -- neuro protection as well, multiple pathways, which are targeted with one single treatment holds a lot of promise.

[indiscernible] .

So should I take it? Yes. So one of the things you have to understand is, first, we have to establish why someone has gone blind. And the blindness has come from loss of tissue already. And then the definition of blindness is legally blind or completely blind and so on and so forth. But once the issue 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 wet retinitis pigmentosa, it reverses itself comes from outside in, you preserve one 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, these are 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 offset of 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 lighted conditions. But why do these cones die? And that's where the whole pathway of multiple things going into damaging the cones. So preserving the retinal tissue is the key. Storing the tissue is a whole different kind of treatment paradigm.

For retinitis pigmentosa, some patients do report in through vision. And I had one patient this last week that told me that he can see better in 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 -- 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.

And just to add to that as well. We know that some areas, unfortunately, the cells have completely died, and we know we can restore those. But some of them are just sick, not quite dead cells. And we suspect that gene therapy can help us modify dose to not potentially reach the kind of the end stage. So really help them come out of a sick state to a more healthy state and preserve. And I expect Manny, what I'm hearing from you is often when we do see in retinitis pigmentosa patients, there is preservation, sometimes a little bit of peripheral vision on island. And I -- while I'm not your physician, I suspect you probably had some visual field changes early on or at least a little bit on island and now the therapy has preserved the cells in area or made them healthier in appearance, and that's why you're starting to see in the corner too.

See this, here? I wasn't like here. I can see nothing here. But here, if I have 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. The stretch is an assured don't...

But I think nonetheless, I'm very encouraged to hear that. I think designed Phase I and II trials, we're talking about patients who are all overly losing vision have lost some of the vision. And unfortunately, we have to start somewhere, and it's often more of a disease right now that we are starting with the hopes that we are going to show safety and to a certain degree, efficacy. And I hope as we continue to show efficacy, we'll move into treating patients earlier so we can save the vision even earlier.

Thank you -- we're going to move on the next section, just in the interest of time, and the patients will be around as you're grabbing your box lunch.

Yes. I want to thank our patients once again for taking the time. Thank you.

All right. I'm going to give a quick commercial update. My name is Mike Shine. I'm the Senior Vice President of Commercial for Ocugen. 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. Dr. Bakall talked about unmet need and demand. And what I'd like to do just in 3 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 want to 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 in 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 3 therapies approved just ahead of the approval of OCU400. And that's okay. These treatments like LUXTURNA for RPE65 are very specialized, and that will treat about 2% of the patients that have RP. Johnson & Johnson is developing a drug for XLRP mutation that may address 5%, 6%, 7% of the patients with RP. And 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 U.S. and Europe, and these projections are just in those 2 regions, will not have an adequate treatment. They don't 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 to 3 million patients in the U.S. and Europe. We think it's about 2.5 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 registration and approval. And Stargardt is 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 OCU410 Stargardts. And so again, potentially 85,000 patients in the U.S. and Europe, a greater than $20 billion opportunity. And I just want to make one more broad point, and that is when sometimes when people see those numbers, they think, wow, how can we afford this drug. Shankar talked very early on about the importance of Ocugen, our mission to provide access of 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 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 going to close the formal presentation part of the meeting. I'll invite Shankar up, and I think we're having a brief Q&A with the management team.

Mr. Shankar, if you want to get back to the stage for a second. Maybe if you have any questions for the Ocugen team. You should ask that as well. I'll start with Michael [indiscernible].

Thank you so much, and thank you for the presentation today. So I just wanted to ask with regards to 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 the trial.

Thank you for the question. Let me begin the modifier genes, what we found out in our OCU410 trial before we got the alignment of FDA for Phase II. We didn't see any dose response. We believe these modifier genes, if you hit a threshold, you may get good activity. So they have ability to self-regulate. So that's already seen in OCU410. That's why agency allowed us to just pick 1 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 maybe it's already hitting the threshold.

Yes. So actually, the data that we have presented, particularly for 6 months, that was not only for low dose but also for the medium one as well who we 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 fixed that at low dose is effective or medium doses effectively, it's being seen across all dose levels at least at this point. And it's 6-month of data.

All right. And then just one follow-up for me. Since targeting RORA hits on the four different aspects of the degeneration, do you just have a sense of the degree of comp inhibition that you're seeing for 410, and how that could compare to the purpose-driven complement inhibitors?

Okay. Thank you. Very good question. So complement innovation 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 age, anti-complement protein CD59. So we do see that in ABCA4 knockout or in macular degeneration condition, this particular protein is significantly separated. Actually, in preclinical, hardly, we see anything. And when you deliver RORA, we see up regulation to the normal level. So if you ask me how OCU410 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.

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 9 million or10 million that would be affected by that.

You're talking about Intermediate AMD? Yes, that's a great question.

Less severe, they don't have GA, 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 to GA?

Yes, 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 a late stage then go forward. And the projections we presented are 5 years. It's only a 5-year model. And it's not looking at typically look for 10-plus in a 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 they get this, then we go before. And our goal is not to intervene.

Great. Thank you.

All right. I think we will close the program. Thank you all for coming.

Thanks again to our patients. Really, really appreciate all four of you, Liz, Aiden, Mary and Manny and our great investigators who spent tireless time. And Huma, a fantastic job. She's running all our clinical programs, supporting Arun, Mike, everybody else. And she doesn't sleep. We have 3 programs going on really, really thankful to all our Ocugen employees. And everybody here, thank you. Thank you for coming to the event today. And the presentation is actually posted. It's an 8-k, got filed. And Tiffany will send you an access.