Good morning. Thank you for coming to Ocugen Clinical Showcase. Dr. Lejla Vajzovic, we're a biotech company focused on gene and cell therapies, targeting unmet medical needs, vaccines for public health. Our goal is not only take these game-changing technologies to the market, work even harder to make sure we provide global access to patients who need them. In today's agenda for the meeting today, after my talk, our CSO, Dr. Arun Upadhyay, is going to go through our gene therapy platform and provide you a clinical update, including upcoming phase 3. And then Mike Shine, our Head of Commercial, is going to give an update on market potential for these gene therapies global, focusing on mostly US and EU. And then we'll have a break. Before the break, we'll have Q&A session.
So after presentation, all presenters are going to sit on the stage, then you can ask any questions. We'll have 10 minutes for that, and then we'll have a break, and then we'll have the panel. I'm very excited to, You know, it's going to be moderated by Dr. Ramakanth Swayampakula, we call him RK, Managing Director of Equity Research at H.C. Wainwright & Co. And, we got an incredible panel. I'm very excited about it. Dr. Lejla, is, she's from Duke. She's going to chair our SAB. Then, Dr. Lam, who is a professor of ophthalmology. Actually, he treated the, the star of this program today, the patient, Mr. Manny Fernandez. He'll be on the stage with the Dr. Neena Haider, our inventor of our modifier gene therapies.
So you're going to see, you know, how she developed it, how the patient got treated, and the patient experience. You're going to see the whole thing today with a couple of key experts in the room. So what is Ocugen? You know, we're really making an impact of courageous innovation. We've been around for little more than 10 years, started in 2013, headquartered in Malvern, Pennsylvania. We got around 60 employees. I think we're very efficiently managed. Companies of our size with, you know, multiple 3 gene therapies in the clinic, typically, they have a lot more employees, very efficiently managed. Kudos to our team. They work very hard. We also opened an R&D center in India to efficiently manage our operations and clinical programs. We do have four values. We try to walk the walk: respect, integrity, teamwork, and accountability.
So now coming to, you know, where we are with the programs. We have three first-in-class platform technology, starting with gene therapies. Today's focus is going to be on our gene therapies, but I'll briefly talk about other programs before I get into gene therapies. We do have innovative, inhalation platform technology for vaccines, targeting COVID and flu. Last year, NIAID picked us as one of the few next-gen companies to participate in collaboration with them, and they're going to do a clinical studies, early stage, for our COVID program this year. And, the next one is regenerative cell therapies, another first-in-class platform technologies for cartilage repairs. We got RMAT designation for that, and, we have recently completed construction of facilities because it is an autologous cell therapy. It's personalized medicine. Very excited about it.
It's first of its kind, first in class, and again, that's getting towards phase 3. We got everything ready to go. Coming back to gene therapies, the focus of today's program, so we're so excited about it. Thanks to Neena. You know, that's her life research, got into, you know, we licensed this gene therapies many years ago, worked extremely hard, and now we have 3 programs in the clinic, starting with OCU400, which is going to be in the phase 3 very shortly. Arun is going to take you through that. FDA also gave us Regenerative Medicine Advanced Therapy designation that will allow us to frequently interact with FDA and allow us to accelerate the development and approval process.
The most important thing is, we're the first company, I'm very proud to say, to take this program in gene therapy space for a broad RP indication. And thanks to FDA for allowing us to do that. So as soon as the FDA clears our IND, we're going to initiate dosing patients, hoping to dose them in March, April this year, in the next 2 months. And then OCU410 focuses on dry age-related macular degeneration, big disease burden. The late stage GA has 1 million patients in the U.S. The current therapies, they require 6-12 injections. Again, they do have significant adverse events in some cases, getting neovascularization. So we believe this can change the paradigm, how you treat patients, something which is not only going after, you know, a few thousand patients.
So far, gene therapies, the best gene therapy targets around 6,000 patients. Now, coming to RP, we're targeting like 100,000-200,000 between U.S. and EU together. And coming to GA, you're talking about 3 million, actually, from U.S. and EU. 1 million in U.S., 2 million in EU. It's about 3 million patients you're gonna target. That's a big paradigm shift, how you're gonna treat this. Also, there is a program, Stargardt disease. It's a big unmet medical need. More than 40,000 patients in U.S. struggle with it today, and we're also doing the phase 1/2. And the goal is, this year, we're going to initiate the phase 3 clinical trial, continue to provide updates on that, and then phase 1/2, GA is ongoing, and same thing for Stargardt disease.
We're hoping by the end of the year, we'll be able to see some signal in phase 1/2 trial, and we'll provide updates to the market. So for the last few years, all the hard work, we released many updates to the market last year, starting with the alignment with the FDA at the end of last year, moving into phase 3 for broad RP indication. We initiated dosing in OCU410 geographic atrophy patients. We also initiated dosing phase 1/2 in Stargardt patients last year. Those are great achievements on gene therapies, and this year, we have many, many milestones coming up.
Our goal is not only initiate the program and work even harder to recruit appropriate number of patients into the clinical trial, so that our key goal is to make these therapies available to patients sooner than later. So our target, BLA approval is 2026. So we're going to really work hard to complete the recruitment and complete the clinical trial very efficiently so that this product can be available for patients who are desperately seeking rescue. The next one is OCU410 and OCU410ST, and both those programs, we're going to recruit, complete the dose escalation and initiate phase II and try to recruit the patients in the phase II. Also provide updates to the market by the end of this year. We believe phase I and II itself will be able to see the signal.
Another thing, as a growing pharma company and biotech, we do need support from Big Pharma. Even though some of us came from Big Pharma, we don't have infrastructure for commercial and payers network. And it's really important while we are doing phase 3 for OCU400 for RP, we partner with, you know, potentially big pharma companies. We're actively working with them, and that partnership is very, very important for the company to maximize value for our patients as well as shareholders. So our gene therapies, you know, want to look into all the biotechnology evolution starting in twentieth century. You have penicillin to polio vaccine, and you have many monoclonal antibodies came into the market.
Then early 21st century, we got human genome fully sequenced, and then we got into gene and cell therapies and CRISPR gene editing. First commercial gene therapies were launched, including mRNA vaccines, which saved a lot of lives during pandemic. I'm going to put Ocugen's modified gene therapy platform in the same space. As I mentioned before, traditional gene therapy, including gene editing, CRISPR, is costly, it's mutation-specific, and it addresses ultra-rare diseases. As we are addressing today, taking even RP within the U.S. has more than 100,000 patients, more than 100 genes can get mutated. It's almost impossible for companies to develop 100 products. So that's the paradigm shift.
With the modifier genes, the way they function, looking at the entire network and the gene expressions under that network, we're going to change the paradigm of how you treat diseases, and we're starting with ophthalmology space, and it has potential to treat broad population like RP with many, many genetic mutations, and also going after big diseases such as GA, which has 1 million patients in U.S. alone. And I think if you take dry AMD itself, is more than 200 million. So we are only talking about late stage. So that's the paradigm shift. We're going to continue to develop and bring them to the market in the next few years. Now, I let Arun take over and walk you through specifics of our gene therapy programs and dive into our phase III clinical design.
We're very excited about. Arun?
Thank you, Shankar. Good morning, everyone.
Good morning.
So I think Shankar already talked about the potential of the programs and pipeline we are working on. In this particular session, I'm really going to focus on understanding how, how this is working, okay? And how we are different than other people in the same space who are developing cell therapy, gene therapy, or, or taking different approaches of gene therapy to treat genetic disorders and other disorders. So the way I look at our modifier gene therapy approach in contrast to other approaches, is that the traditional gene therapy approach is either gene augmentation or gene editing. And your approach is, and assumption is that, if you have a mutation in a certain gene, that lead to the disease.
One way to treat that is, like, you give the normal copy of the mutated gene, and you do the augmentation of that copy, so that you basically, you know, make cells or tissue enable them to restore the function, okay, related to that particular gene. Gene editing is more like, you know, you are correcting it, you know. So rather than supplementing something from outside, you are correcting at the place where the defect is. But the limitation of those approaches is not just only that it is applicable to the one mutation or one gene with one product, but also it is limited by the very fact that when you have a mutation in certain gene, disease is not just an outcome of that mutation.
Disease is manifestation of various other factors which get imbalanced, which are not normal as we develop disease, or we acquire the disease during the course of our life... How we understand that? The basic way to understand that, we all, those who have inherited retinal disorder, they have the mutation in those gene since birth. But do they have the disease fully manifested at the birth? No. Do they lose the vision completely at the time of birth? No. These are so slow, progressive diseases. What might be going there? There must be something else, because if gene is mutated, that function is impacted at the time of birth, but the impact of the clinical manifestation, or what we call phenotype, associated with the mutation, is not present at the time of birth.
It means there are other factors which are responsible, which modulate how a mutation may lead to the disease. That is where the modifier concepts come in the picture. Now we are understanding that in not only in this particular disease area, but in other diseases are also, where I think scientists and this whole community is talking about epigenetic regulation, other modulation, bringing the homeostasis, bringing the balance. Disease is all about imbalances in the various, whether it is at the cellular level, molecular level, biochemical level, whatever level you can think of. It is some way imbalance in the system. So what modifier does, in contrast to other gene therapy approach, that in the retinal disease condition, especially for our modifier gene therapy program, it brings the balance.
It restores the balance, and by restoring that balance, we are able to either improve the function, lost function, or you stabilize, at least you, you prevent the progression of the disease. That's the whole concept. So keeping the... And, and how this work? The genes are master regulators, because there should be a way, like, how they are, how they are regulating multiple imbalances. So the way they regulate, because these are master transcription factors, and they not just impact one pathway, but they impact multiple gene network, which, which Neena, our inventor, she, she has kind of explored during discovery work, and she's going to talk about it. So this is the whole concept. So goal is to restore the imbalances in the various gene network or molecular pathway, which are impacted in the disease condition.
By doing so, you are able to basically provide the treatment benefit to the patients, and potentially in terms of restoring lost vision or by stabilizing the vision. We have two products in that particular pipeline in development. One, OCU400, that we are developing for retinitis pigmentosa and Leber congenital amaurosis. Another product we have in the pipeline is OCU410, that is based on another modifier, RORA. That molecule we are developing for age-related macular degeneration. Currently, like advanced form of age-related macular degeneration, that is geographic atrophy. Recently, we are also developing this for a genetic disorder called Stargardt disease.
The way this molecule, similarly like our OCU400, this molecule also targets multiple pathway, which are impacted in this disease condition, macular degeneration condition, like complement pathway and inflammatory pathway, oxidative stress pathway, altered lipid metabolism pathway. So all these pathways are regulated. They are altered in the disease condition, and they are bring back to the balance, when you treat with the RORA. So this is just high-level overview. Like, more than 125,000 people are impacted by RP and LCA in the U.S. alone. And if you look at the global prevalence, it is in millions for RP and LCA. And another thing, which we need to keep in mind, that all these diseases, you know, it's not one gene.
You have, like, hundreds of genes impacted or mutated in this disease condition. And as we mentioned, like, if you want to kind of develop a therapy, gene-specific or mutation-specific, then it's such a daunting task that is almost impossible to achieve in a reasonable timeframe. And also, like, if you look at where the current unmet medical needs are, so far, in this field, we have been working for last, you know, close to 10, 20 years, but we have only one product. And that product is just able to take care of only very small fraction of the patient population. I'm talking, like, few hundreds. So there is such a significant unmet medical need in this space.
So our goal and our belief is that based on the mechanism of action of the, our modifier approach, that this molecule has potential to provide benefit to not only hundreds of subjects, but thousands and thousands of people who are impacted by retinitis pigmentosa and Leber congenital amaurosis condition, and much beyond in other disease area, such as age-related macular degeneration and Stargardt. As Shankar mentioned, like, we have been in constant interaction with the regulators related to the further development of our OCU400 pipeline. We have a good alignment with FDA on our overall study design and primary endpoint, and we are advancing to the phase 3 clinical development for this particular molecule. Our design is based on favorable safety and efficacy profile in this patient population.
That has been the basis for us to move forward with the broader RP trial. And this is the first trial which is going to be gene agnostic, purely gene agnostic in nature, not just like covering one or two particular mutation, but pretty much all the known mutation in the RP space. And the follow-up for this study is also not longer, it's just one year after the treatment. So we expect that trial is going to be shorter, and hopefully we'll be able to get the molecule in for market authorization in 2026. So this is a high-level safety and efficacy summary from our phase 1/2 study, primarily for RP patient. So far, we see that OCU400 is generally well-tolerated and safe across all dose levels.
So we tested three different dose levels in Phase 1 study. Not only that, it is also well-tolerated across multiple mutations. It is not just a dose level, but dose levels are also tolerable across multiple mutation. And we also noticed that most of the patients, they showed improvement or stabilization on various parameter linked to the visual function or functional vision, such as best corrected visual acuity and LLVA and also the real-life mobility course, you know, under different light conditions. 89%, 16 out of 18 RP subjects, we saw that there is a stabilization or improvement in the vision on either of these parameters. And when we further looked at the mobility course, which has been kind of a biomarker or the endpoint, which has been used for the approval of the Luxturna.
Even on that parameter, we see that close to 78% subjects showed a stabilization or improvement. When we further do the sub-analysis, and why I'm stressing sub-analysis? Because I did mention about modifier function. It's not gene augmentation. For RHO subject, this product is gene agnostic, because product is NR2E3, and we are treating the RHO subject. So even in that gene agnostic arm, in phase 1/2 study, we have 80% RHO mutation-associated subject experiencing either stabilization or improvement on mobility course. And this is fantastic, actually. This also tells about how modifier can really modify the disease and provide the treatment benefit. So coming back to... So based on those phase 1/2 study outcome, we moved forward with the phase 3 design.
So this phase 3 study is going to be multicenter, randomized study to assess efficacy, safety, and tolerability of subretinal injection. This is going to be the assessor-masked study. As you all know, in the subretinal surgery, we cannot mask the control, so it is going to be assessor-blinded study. As I mentioned briefly, what is the approach? What is the goal for us to these patients? Our goal is to stabilize or provide improvement in the vision. We are not just looking for stabilization, we are really looking for improvement. Our phase 3 is designed to provide benefit, not just a stabilization. That's how our primary endpoint is designed. We want to demonstrate that this molecule does provide the benefit in terms of functional vision to these patients in our phase 3 trial.
This is the phase 3 study design, where I'm going to spend some time with you all. So our trial will consist of total 150 retinitis pigmentosa subjects. These subjects will be qualified based on not only their clinical phenotype, but also will be confirmed through the genetic diagnosis that they are RP patients. And in this trial, we are going to enroll subjects 8 years and older, so it does include pediatric patient population, not just adult. Those 150 subjects will be equally distributed between 2 arms, the rhodopsin gene arm and the gene agnostic arm. The reason for us keeping rhodopsin arm is that this is the arm where we, in the phase 1/2 study, we had quite a bit of subjects. So to also de-risk the trial, we wanted to have a separate arm for the rhodopsin.
So that's why you see the rhodopsin arm alone. And then another gene agnostic arm, which will consist of all the patients with different kind of mutation linked with RP disease. And further in each arm, these subjects are going to be randomized 2-to-1, to receive either active treatment of OCU400 or as untreated control. And after, like, treatment, these subjects are going to be followed for a year, and that is when we will be doing the primary endpoint assessment. So primary endpoint is linked to the change from baseline to the one year endpoint assessment. And our plan is that once the primary endpoint analysis is complete, we do the BLA filing. At the same time, it is not good that you leave the untreated control, okay, without any benefit.
So as a part of her study design, this untreated control subject will be offered to cross over to the treatment. However, this crossover decision will be made only after we analyze the treatment benefit in the treatment arm for these subjects. Only then those things will be offered to them. If you look at key eligibility criteria, we are covering the broad range of the retinopathy, the subject with, say, significant vision loss to those who are even early stage of disease. And also, as a key eligibility criteria, we are performing the LDNA. LDNA is basically modified mobility course. It is luminance dependent navigation assessment. And this is different than the MLMT course we used in phase one, two, which I'm going to talk about in detail in later slides.
Our goal is basically to implement this test, because we want to really eliminate the ceiling effect. Because a lot of subjects, what we learned in our phase 1, 2 study, that they are able to pass the course at the lowest light level. And that was the primary reason for us to basically modify this test and come up with the new range for this particular for phase 3 study. And our primary endpoint is going to be proportion of responder, which is defined as 2 lux or more improvement from the baseline at 1-year time point in treatment versus control arm.
As a part of secondary analysis, we are not just looking at the responder just in the study eye, but we are also going to look at all the treated eyes in the treatment arm and compare between treatment and control. Another parameter we are planning to look at in as a secondary endpoint in this phase three study is low luminance visual acuity. Why it is so important? Because in the retinitis pigmentosa, as you all know, nyctalopia is one symptom. Like, we start, you know, having difficulty with the night vision. And LLVA is one of the test which does capture that particular deterioration, so it is sensitive to that low light condition. That's the difference between BCVA and LLVA.
When we look at the statistical consideration, how this phase 3 study is powered and what is the possibility of, you know, success for this study. So as I mentioned, this study will have total 150 subjects and 75 in each arm, randomized 2 to 1. But this sample size is sufficient to achieve the statistical power in this study for both arms, RHO and gene agnostic. And assumptions are that we are assuming that 50% will be responders in the treatment arm. And when I say 50% is responder, what does it mean? That if you dose 100 subjects, 50 subjects will be able to demonstrate 2 or more lux levels improvement at the 1-year endpoint.
For the untreated control, we took the responder criteria of 10%, and the reason, because always in any trial, you know that it's progressive disease. You don't expect untreated to gain any function, because that's not the nature of disease, but somehow, like, you know, it's random, what you call false positive kind of response. So to account for that, we took 10%, you know, in our sample size estimation. This study is powered more than 95%... 90%, 90%. Our hypothesis is basically to demonstrate that response rate is higher with the treatment group compared to the control in RHO subgroup. And also, as a part of conditional efficacy hypothesis, we are going to demonstrate that response rate is higher with the treatment compared to control in gene agnostic group as well.
Now, you learned about our phase 3 study design. I would also like you to understand what was the basis for that design, what data we used to make that decision, and to consider those responder criteria and other assumptions we made in the design consideration. So, as I mentioned, we had 18 subjects in phase 1/2 study. But out of those 18 subjects, 8 subjects meet our criteria, intent-to-treat population criteria for phase 3 study. And this population represents, you have RHO as well as NR2E3 mutations. But before I go into the data, I really want you to pay attention to these two KOLs, one like in orange and blue. So the orange scale, MLMT scale, which we used in the phase 1/2 study, and when we started the study, that scale was only from 0 to 6 lux level.
Even the 7th, what you see, 0.1, we introduced much later in the study. So most of the subjects by that time had already enrolled, but we wanted to, you know, capture some additional data for that. The below scale is LDNA, which we are going to use in the phase 3 study. You can clearly see the difference, not only the number of lux levels, which we have in the newer scale, is much more compared to the old. But in addition to that, if you look at the spacing of the lux intensity, is much uniform. It's uniform in the newer scale compared to the older scale. So in older scale, like lux level improvement is not that homogeneous for a given light intensity. So those are the two changes we made.
So, we wanted to look at our data to intend to treat population, how they respond in the newer scale. And it's just mathematical conversion, by the way, okay? For you all. There's nothing like that we ask patient to do the like, you know, walk the new course, but it is simple mathematical conversion of light intensity to the lux level, okay? And as you can clearly see, that most of the RHO subject here, we see that they are responding more than 2 lux level. Not only that, some subject, if you look at, like, two RHO subject, we see the lux level improvement 3, even on older scale. And when we convert that data to the newer scale, it becomes 4 lux level.
When you look at autosomal recessive NR2E3 population, we do see that in, on older scale, we have one lux level improvement. But why that was restricted to one lux level? Because for these subjects, baseline itself was at the five. So when they improved one lux level, you reach to the ceiling effect of the older scale. So even though there was a treatment benefit, but you don't see two lux level gain because of the ceiling effect of the assay, at that time. And overall, when we also look at other parameter for these subjects, like BCVA and LLVA, we do see that on all these three parameters, these eight subjects either demonstrate a stabilization or improvement... And further this slide, again, to reiterate the gene agnostic mechanism.
Further, I narrowed down to this RHO population, and if we just focus on RHO population, you can see that more than 50% intent to treat RHO population meet responder criteria. And that is what has been the basis for our phase 3 design. Clearly, our phase 3 design is powered based on the phase 1/2 data, which indicates that with this assumption and sample size, we should be able to meet the primary endpoint if the molecule does the way it performed in the phase 1/2 study in intent to treat population. This is what our overall plan is for this particular program. We are planning to initiate the phase 3 trial this year soon, and the indication is going to be treatment of retinitis pigmentosa. It's a broader indication.
In addition to that, we are also expecting to pursue LCA indication in second half of 2024. As you all remember, as a part of our phase 1/2 study, we have LCA patient also enrolled, but data for—we are waiting for the data for those LCA subjects, one-year data point. And once we have that data available, then our plan is to have interaction with the agency and potentially initiate the phase 3 trial for LCA also this year in the second half. So, with that, I'll pause and I'll invite Mike Shine, our commercial head, to talk about our commercial projection for the molecule.
Thank you, Arun. Good morning.
Good morning.
So based on all the data that Arun and Shankar shared with you, we've taken some initial efforts to try and put a value, a market assessment on our OCU400. And as a commercial guy, this really excites me because the upside potential is quite terrific with a gene modifier therapy. It doesn't suffer from the same things that gene editing and traditional gene therapy suffer from, which is very small patient populations, where $ millions have to be charged because that population shrinks as those patients get treated. So in this analysis, we looked at sort of standard market penetration over a five-year period, ranging from 3%-15% in the U.S. and Europe. We looked at the pricing assumptions based on current modeling for gene therapies, and, you know, the number's big.
It's $47 billion of cumulative revenue over the first 5 years from 2026 to 2030. So we pressure tested it a bit, and we looked at a downside scenario and said, "Well, what if we just price it parity to Luxturna, the current only approved therapy in RP, indicated for RPE65?" And using that as a proxy, we can see 5-year revenue of $30 billion. While those numbers look very large, I think there's a broader and more important point here. What this really proves, because you can toggle the penetration numbers, you can toggle the price points, you can drive them down and take them up, but what this shows is the value of modifier gene therapy. There's 175,000 patients in the US and Europe with RP and LCA.
With a broad indication, we have the potential to reach a very large patient pool, and you don't get that with traditional gene editing. So while the numbers are impressive, the real value calculation here for modifier gene therapy and how it's different, as Shankar alluded to earlier, than traditional gene therapy, is the size of the patient pool. And it's even more extreme when we look at geographic atrophy. I think Shankar mentioned the number of 3 million patients in the U.S. and Europe with geographic atrophy. And if we take really a nominal penetration rates, and again, pricing that would be considered at the very low end of gene therapy pricing, you're still seeing calculations that show the value of this therapy in the range of $75 billion in, in revenue. And so, sometimes these numbers look, you know, almost, overly impressive.
Certainly from a commercial standpoint, it gives us a lot of range and a lot of flexibility. But then some people might say, "Well, how are those people going to access it?" And I really want to make an important point here. Shankar pointed out that our mission is access, and one of the great things about having gene therapies that can be used for large patient populations is it gives us enormous flexibility on pricing, and it allows us to guarantee that regardless of ability to pay, we're going to be able to make these therapies available to patients. So we are working already on payment plans, and strategic access plans that will allow these gene therapies to be used by patients who couldn't afford these prices.
But in order to establish the value of the gene therapies, we had to run these models using the traditional gene therapy approach. And again, what it just offers the company? Incredible flexibility with pricing, penetration, and access. And, those are my only two slides. But I, I want to close on something again, just to reiterate that point. These are valuable technologies. We're changing the paradigm of gene therapy. It's no longer one for one, treating a mutation, and if you don't have that mutation, you don't get a gene therapy. In RP, we're developing something that can be used for patients regardless of their mutation, and they'll get a benefit from it. That's got enormous value, but it only works if the patients can access it. So again, just to reinforce the point, in our mission, you see access as a priority.
In our vision, you see that Ocugen is intending to become a fully integrated, patient-centric biotechnology company focused on vaccines for public health, cell and gene therapies for unmet medical needs through courageous innovation. We take that very seriously. With that, I will close and invite Shankar back up.
Yes, so now we're going to open it up for some questions.
Any questions?
Yeah, this is RK from H.C. Wainwright. Shankar and team, thank you very much for doing this. When Arun was talking about the data, he was also talking about the subset of RHO patients. So just for us to understand, what percentage of RP patients end up having RHO mutation?
... It's about 10%-12%, around 10,000-12,000 patients.
Thank you. And then, you are introducing LDNA as an endpoint and now in the phase 3 study. Has LDNA been used by any other entity as a primary endpoint, or is this something that we need to teach FDA how to deal with it?
I don't think we need to teach that to FDA because with this particular test, we came up with in the collaboration with FDA. And this test is no different than any visual mobility course. The difference is not as such in the principle of the course, but more like what this course can cover in terms of reducing the ceiling effect, or you can say, potentially eliminating the ceiling effect, which we see in some of the subject. And also providing the range so that you can enroll a lot of RP subject, which could be potentially eligible for this treatment. So not new. We don't have to do anything extra to establish that this could be a primary endpoint.
This is something which FDA is fully aware of, and it has been put in place with the FDA alignment, with their recommendation and discussion with us.
Any other question?
Yeah, Robert. Could you pass it back, Robert? Thank you.
Just a question on the clinical trials. You just mentioned that the RHO mutation is about 88%-90%, and in the trial it's going to be mutation agnostic.
Mm-hmm.
You have RMAT designation for the RHO mutation. So I'm just wondering how the design of the clinical trial would fit with the RMAT designation and the benefits for approval, and then how that fits with your post-marketing plans and addressing the entire population. Would you have approval for all RP patients? And just how, how the designation fits with the commercial plan and the clinical trial?
I'll answer the first part of it, then I'll give it to Arun. The clinical trial, we got RMAT based on phase 1/2, because we have retinitis pigmentosa patients in there, NR2E3, and that's what they covered. So now we're going into gene agnostic. So eventually, we can get RMAT for that in future. And our goal is to get the broad RP indication. That's how the clinical trial is designed, RP and gene agnostic. Those are the two groups, and we already have orphan drug designation. So that will help to accelerate the approval in six months, irrespective of what the data comes out in either group. So with that, I'll also give it to Arun.
No, thanks, Shankar. I think you pretty much answered. So you just mentioned RHO, I think, in question. So our RMAT is for RHO and NR2E3, both, okay? Just, so both populations, which were part of phase 1, too. And, as a part of approval, the way a study is designed, as I mentioned, if you, if you, if you look at the hypothesis, the primary hypothesis is to demonstrate the efficacy in the RHO. And once that is made, and when we demonstrate further the efficacy in the gene agnostic arm, then FDA in alignment to give the broader approval. Okay?
Okay.
Yeah.
Okay. Yes.
Yes. And whether RMAT can be extended to the gene agnostic, always, RMAT extension is based on the clinical evidence. So once we have that clinical evidence in that group of patient population, then definitely we'll apply for that and we'll have-
Okay, I see. That's an important point.
Yeah. Yeah.
And the clinical trial-
Yeah
is designed so that it could... All of these designations could be extended...
That's correct
- to the entire population-
That's correct
not just what you have designation for today.
Exactly. Exactly. But already we have other designation, which applies to, to the broader population. So we have Orphan Drug Designation from FDA for RP disease, not for mutation-specific RP disease. So we have broader RP Orphan Drug Designation. We have broader LCA Orphan Drug Designation from FDA, and similar designation we have also received from EMA for broader RP and broader RP and broader LCA.
Okay, great. Thank you.
Mm-hmm.
Robert.
Hey there. Thank you. Michael Okunewitch from Maxim Group. So I guess for my first question, I'd just like to see if you'd comment a little bit more on pricing, and specifically, would you expect there to be some pressure from payers to price a little bit below where some of the ultra-rare gene therapies are targeting, given just how large your indication is in comparison?
Oh, Mike?
The answer is yes. We always expect price pressure and negotiations with payers, so that is a given. I think what we tried to do for this initial run was look at all of the existing data and models and plug in without really considering initially patient population. So we looked at quality-adjusted life years. We looked at potential improvement in quality-adjusted life years. We applied the ICER model. You saw some references at the bottom of my slide. So we've been fairly exhaustive in this first run, and I think what's encouraging to us is there's so much head space for pricing because the population is so large, that ultimately, because we are committed to access, we're going to be able to find a price that everyone's going to be satisfied with and is going to give a very significant return.
Yeah. Thank you. And then, as a follow-up, I just want to ask a bit of a stats question. When looking at the powering for both arms in the phase 3, are they powered against each individual control group, or is there a pooled control group that you're comparing?
Very good question. Individual control group.
75 subjects in each arm will be randomized 2:1.
Mm-hmm.
Each arm has their own respective control. 50 in treatment and 25 as a control. The power is 50 versus 25.
Mm-hmm.
not 100 versus 50.
Okay, thank you.
Any more questions?
Hi, just a quick follow-up to Robert's question. Wanted to confirm for the phase 3 study, would you still hit your primary endpoint if you got improvement in the RHO population, but not in the broader RP population?
That's correct, and that's why it is a conditional-
Okay.
efficacy hypothesis that will be tested only if RP patient meets the primary efficacy endpoint.
Perfect.
Yeah.
Thankful.
And-
Go ahead.
Yeah. Yes, that's-
Just two quick follow-ups. I think the first one here is just, are there other things that you've modified in terms of the baseline patient criteria from the phase 1/2 to the phase 3?
Yeah, we did, actually. So, so one of the important criteria is related to the primary endpoint, test itself. So in our phase 1/2 study, we enroll the subject, you know, anywhere between someone who is failing at the higher lux level to even passing at the lowest lux level.
Mm-hmm.
But for this trial, if you look at our LDN course, the range, we have starting from 500 lux-0.004 lux.
Mm-hmm.
The way we are setting the inclusion criteria, that anyone who fails at 0.35 lux intensity-
Mm-hmm.
- will not be eligible. And why? But again, at the same time, we are increasing the range. You can see. Someone failing at 1 to now, we came down to 0.35. So it will allow us not only to enroll wider group of RP patient at the different stage of disease, okay? But also it gives us a window to demonstrate the treatment benefit. So anyone, say, who fails at 0.35, it means he must have passed at 1.
Mm-hmm.
That's the next level. So from 1 to 0.04, we have total 3 lux levels to demonstrate the benefit. And our criteria is 2 or more, okay? So that is how it is different.
Perfect. Thank you. The last one here, I'm gonna put you on the spot a little.
Okay.
The data looks really interesting. So you have LCA data coming up. You know, what do you think your efficacy is going to look like relative to Luxturna?
Good question. So in our, the current LCA trial, we are not enrolling the subject what Luxturna enrolled. So Luxturna trial was focused on a particular mutation, in a gene called RPE65. Our current LCA trial is, with the patient CEP290 mutation. And, CEP290 gene mutation is one of the most and common prevalent mutation in the LCA patient population. Now, coming back to how it will fare, okay? If, we have to look at the, the lux level improvement. Of course, it is early to say, but so far, whatever we are seeing in terms of modifier, I think, I'm quite hopeful that we'll see something. Yeah.
Any other questions?
Any other questions?
Hi, I'm with the American Macular Degeneration Foundation. Looking a little bit further down the road to OCU410, what's to prevent the same molecule from treating the disease at much earlier stages, even as early as early AMD, if it's been identified?
I mean, it doesn't prevent... I mean, obviously, we need good diagnostics.
Mm-hmm.
I mean, currently, you know, there are two products you gotta put in the market. They look at the lesion, so you need to identify. If you come up with a biomarker, that's where we want to go. And, somehow, if we can identify early stage, we can prevent it. I think that will be the future. Agree.
Got it.
Hundred percent.
Yeah, I think it's gonna be an amazing development because that population is huge.
Agree. Agree.
Okay, any more questions? All right, we're gonna take a short break if everyone would like to get some refreshments.
Thank you.
Then, yes, thank you, our speakers. So take a look-
Also, Tiffany, just a moment.
Yeah.
I would also like to really, you know, we are very thankful, and we are really would like to acknowledge inventor and our investigators, and all the clinical sites, and the patients, and everyone who has been part of this incredible, I think, phase one, two study. Now, we take pride, and we take pride in completing this study in such a short span of time, not just because of what we do, but also, like, all the support we get from you all. Everyone is so important, our investigator, our patient population, and all the advisors, KOLs, and everyone. So thank you. Thank you all for your support.
We'll start back in a few minutes with our panel. Hi, everybody, I'm Tiffany Hamilton, Head of Communications at Ocugen, so I oversee IR and PR for the company. I think I've spoken with most of you, so it's nice to meet you in person. I'm gonna do a very, very brief intro of our panel because we had their bios on the screen during the break, and I cannot do any of them justice. First off, I'm gonna introduce RK, who is Managing Director of Equity Research at H.C. Wainwright. He'll be moderating the panel. We have Dr. Neena Haider, who is the inventor of modifier gene therapy. Then we have our patient, Manny Fernandez, who is a patient of the phase 1/2 clinical trial, and he'll be sharing his experiences. Dr.
Lejla Wajsarowicz, and she is a retinal surgeon at Duke and a lead expert in this space. We also have Dr. Byron Lam, who's at the Bascom Palmer Institute at University of Miami, and he's our lead investigator from the phase 1/2 study. Hand it over to RK.
Thank you, Tiffany. Good morning, folks. So just to get started with this panel, and I'm gonna ask Dr. Haider to define for us again what modifier gene therapy is. I know Arun just did a great job, but just to get this started.
Great.
What is modifier gene therapy, and when you got started, what were the benefits that you wanted to get out of this?
Wonderful question. And, Arun, you did a great job earlier defining what this is. I'll expand on that definition, and I'll start by telling you, very lay terms, what is a gene? A gene is a coded part of your DNA. We have about 30,000 of them. I was part of the Genome Project, and when we were first doing it, by the way, we thought there were gonna be 100,000. And then as we sequenced more and more, we're like: "Oh, there's less. There's 50,000. No, there's only 30,000." They work in concert. They work together. You don't have all 30,000 expressed that make a protein. Protein does the work in your body, and they don't all express in every part of your body.
The retina, the camera of your eye, which is the focus of today's conversation, actually expresses maybe one-tenth of them, 2,000-3,000 of these genes. So what a modifier gene is, it's one of these 2,000 or 3,000, but it's a master regulator. Think of it like the master conductor or a circuit breaker. It regulates several hundred to 1,000 of these genes, and it can make things worse sometimes. It can make them better. It's a balance, depending on how your particular genetics works, right? What particular changes you might have and the nuances of them.
When we first started studying modifier gene therapy and the impact it could have on the human condition, that was actually a really next step of profound discovery science that happened, that in the context of, say, a disease mutation, something that will cause a detrimental effect, in the presence of that, there were other genes that if you have a particular variant of that, you never saw disease. Now, we saw that in the early 2000s, and that was what led me to today, that, wow, we can have, in the presence of mutation, completely disease-free retina, and it can function normally.
That's the power of the modifier gene therapy, and that's what, when we talk about what we were thinking in the future, we saw this in many models, that we can just by having particular part of the DNA gene be a variant that can normalize and stabilize, and we can talk more about that if you want. The homeostasis, like, just like everybody during the pandemic wanted to go smell the flowers, take a walk, and do yoga, every cell in your body also wants to be zen and wants to maintain the state of normalcy, and that's what they help do.
Thank you. And so, within the modifier gene therapies, you also focused specifically on NR2E3, you know, as the potential gene to regulate these conditions, whether it's in RP or the LCA. So, we don't need all the details of the mouse experiments, but in general, how did you land on NR2E3?
Oh, that's a, that's a fun question. There were several of these modifiers, right? There's not just one. How did I land on NR2E3? It's a class of genes that are master regulators. It's in that class. There's about 52 of them. And this one, in particular, was really expressed just in the retina, whereas most of them are expressed throughout your whole body normally. And I thought, okay, this is something if it can master regulate, will have such a specific effect on that part of the eye, that I thought it would actually be a more potent and powerful therapeutic option because that's where it's expressed, that's where it's master regulating. And in the context of diseases where something like RP or LCA, you have hundreds of roads to get to this.
My driving force was always there's about 30%-40% of patients that will never have a molecular diagnosis that can tell them, this is your mutation, and feasibility of making 200 therapies is not still very realistic. How are we gonna help those people that have nothing? And that was kind of the driver for it. And NR2E3 being this master regulator that had a specific function in that area was why we chose that.
Thanks. And then you spoke a little bit about this, in terms of homeostasis. You know, we know that NR2E3, being a master gene, regulates multiple functions, including retinal cell homeostasis, metabolism and visual cycle, and me being a toxicologist, I always worry about adverse events. So, since it regulates so many different mechanisms, so what sort of adverse events would you be on the lookout for when you're treating with the modifier gene therapy?
So it comes back to another reason why we chose this class of genes and NR2E3 in particular. We do these large studies and publish papers, and there's always this little tiny data. Those are my favorite figures in the papers. NR2E3 self-regulates, so you don't have to worry about having too much of it. And that was a bonus reason why we also choose, that addresses that problem of how is it gonna have a toxic effect? Many of these, this is why we chose this class. They actually autoregulate, so you don't worry about having too much. They regulate inflammatory response, they regulate, not just cell survival, but cell death and neuro, and protection. So because of the things they were regulating, we didn't really have a great concern in terms of was it gonna be toxic.
In our preclinical studies, we saw in many, many models, and I'm talking about thousands of studies here, no toxic effect. And so I was very confident that that would not be an issue.
Thank you for that. So moving on to the disease itself, Dr. Vajzovic, how would one define inherited retinal diseases? And, what's the incidence of RP and LCA, not only in the United States, but also worldwide?
You know, I think we heard that very well earlier from Arun kind of summarizing. Really, inherited retinal diseases is a group of disorders with very, various types of, genes involved. And because of the diversity, it's a challenging problem for us, in a sense, to, to find treatment or, or options for those patients. It is a rare disorder, but one that's, across all genes, quite prevalent, and as we kind of saw earlier in numbers, you know, 1.5 million across globally. And, LCA specifically is a smaller number, but one that's clearly, if we're talking about all the genes that are affected and involved in inherited retinal diseases, it's, quite a few patients, for certain.
In terms of that diagnosis itself, you know, how easy is it to diagnose these patients? Once you diagnose one patient, since it's an inherited disease, do you start questioning the patient and his family and, you know, immediately you get to see multiple patients within that family? How often does that happen?
I think ever since, with the emphasis on gene and eye, understanding genes that are involved, you know, we talk about retinitis pigmentosa, LCA, but we really should be talking about gene-specific disease and redefining how we define these diseases to begin with. But that we are moving to that direction, and there are about 280 genes that have been described in IRDs per se, and they're being caused... And more and more now, we're basing our clinical diagnosis earlier because we are defining it by doing genetic testing. We used to not be able to do that to the same degree.
That definitely has changed the paradigm we practice, and nowadays, you know, we can do a simple saliva testing, just send a kit to a patient, you know, via mail, and even do a virtual appointment to help them actually identify this disease. And knowing that it runs in the families, of course, we encourage family members to get tested and broadly. So I think it's defined from... It used to be, these patients come to our office with lay diagnosis because of the fact their vision is now affected, and we start, you know, figuring out things at that stage. Now, we are seeing these patients much earlier because of the genetic testing.
I think I know the answer, but still, I think I have to ask the question. Obviously, for these IRDs, is there a therapy or you, even though the patient comes to you, you've got to give them something, and what would that be? Is it more, how to manage life physically, or is there a real treatment of some sort?
Yeah. You know, I think it's a challenge for certain. First, we used to have a challenge of diagnosis, but, you know, once you're diagnosed, it's really become more of a counseling session, unfortunately, 'cause the options are limited. We really have Luxturna as the only option currently for one gene specific. And it comes down to really doing more of a discussion of like, what the prognosis may be in this case, involving our visual rehab center, to help really these patients learn how to function with the vision and what future may hold, and to empower them with resources outside of treating the disease, such as, you know, low vision assistive devices to help them really function to the best ability they can with the vision they have.
Thank you. Mr. Fernandez, how did you find out that you have RP, you know, and what age, and how has the journey been with the disease itself?
Well, we have generations in the family that had the disease. I do not know for sure if my great-great-grandfather had it, 'cause there was no information. I don't have any information. I know my grandfather did, my father did, and his other three siblings. Now, my generation, we have three brothers, and two of us have the disease. Mine always- I came along to the United States, and I knew about the disease. So every time I went to the eye doctor, I told them about it, and they couldn't find anything until I was. I can't remember if I was 40, 43. They start looking at spots in the eye, and that's, you know, when I realized that I had it. At night, it was not so difficult.
It's been increasing more and more, the vision decreasing, and I don't drive at night anymore. So, that's... But I wanna do something. So everybody has a white page in there? I hope you,
No, no.
Let me do that.
Nope. Go ahead.
I want you to write—to draw an eye in the, in the corner. This is homework, okay?
Homework.
I want you to punch a hole on the corner, two holes. I don't care how they are. Just punch two holes. Now, this is what I want you to do. Put it on one eye and look at me. That hole is too small. What can you see? What can you see?
Not a whole lot.
Not much, right?
Yeah.
That's what I can see. Okay?
No peripheral.
No. Thanks to Neena. I have... this is my actual vision here. So you know, you can see it later if you want, where I can see through. Thanks to Neena. I was-
Yeah.
I've been in this story for about a year and three months. For the first time, about a month ago, I was driving, and I always try to drive safely, you know, on the right side of the road. And I saw something going through, you know, and scared the hell out of me... 'cause I'd never seen that before. Right now, I cannot see what it is, but I see a shadow somehow. I can't explain, but I see a shadow, and that is amazing, you know?
It's a car.
Well, it's obviously it was a car, and, you know, and, before I couldn't see that, you know, I always had to look at the mirrors to see where I am and how the traffic is. So that little thing, for some people, well, probably 100% of you, don't realize how big it's for us to be able to do that. But not only that, this eye, which that's the one they performed the surgery, which I call a bacteria. I didn't know it was a gene. They, they, they started... I forgot what I was gonna say. I'm sorry.
The treated eye.
The treated eye was the worst.
That's why they treated it.
Now I can say that it's better than this one. Okay? It's better than this one. And it's... You know, I'm ready for the other one already. So,
It's a matter for you.
That's what I wanted. Thank you, Mr. Fernandez.
Would you like water?
Hmm?
Would you like water?
No.
Okay. Thank you.
Thank you.
You're welcome.
I was gonna ask you how the journey was. I guess you already answered the question, so thank you.
Sorry
... very much for that. Thank you. So this is a question for the full panel. So as we understand RP, I know it does progress with age, but then... But we see different differences among the different patients. In general, how do you attribute that difference? Is that more on the number of mutations, or is it how it gets manifested, or does it depend upon what modifier gene is actually running the show?
Mm-hmm.
Any comments, please?
I can start. Yes, it matters what type of mutation. It matters, the context, right? The biological load, that's how actually it's in another terms. One of my marketing people says I should start trademarking things. But it's rather than thinking of this, and I think Lejla brought up a great point, these diseases, as they were being discovered, were assigned names and put in boxes, but that's not how it works in the body, in the system. They work in concert with thousands of genes together. And so it's that whole mutational load on a biological system. That means that primary mutation, any modifier effects, epigenetic. You're a product of your DNA and environment. How all of that interacts in a very personalized, precise manner, then determines your clinical outcome, and therefore, will also determine the robustness and the outcome of any therapeutic.
If you both can expand on that.
Well, so, sure. So I can also add, I think the spectrum of the disease severity is also depending on which point the specific gene, which DNA point is affected, and that has a different effect on the protein. There are so many factors that are mentioned. You know, there's the modifiers and so forth. But, you know, let's say somebody have a NR2E3 gene-related retinitis pigmentosa, but you can have a mutation at a different point, and that in itself causes changes in the protein, which we can try to predict either through a computer model or actually find patient with a specific mutation and gather them and find their specific effect in how they actually progress in, in terms of their condition.
But when you think about that, you say, "Well, that's really daunting, then how do we do clinical trials?" Well, you do clinical trials because first, you can pick the genotype. Second of all, you can have inclusion criteria, like, I just want to pick patients who have this amount of central vision, this amount of peripheral vision, this amount of ability to do the mobility test in a certain range. So that in itself is very important in a clinical trial, right? So you can then have patients who are appropriate, who can then fit into the therapy you have in what we call the therapeutic window, you know, that range of patient that we believe the treatment can absolutely work.
Anything from you, Dr. Vajzovic?
No, I couldn't agree. I think it's such a diverse presentation, and just like was alluded and Dr. Lam beautifully described and says that you may have that specific gene involved, but what point is it really mutated, and what kind of protein production is that? But not only does it affect the protein, but everything surrounding that, modifiers, and also your exposures and environment for certain dictate that. So while we, you know, lump all of that in one category, even within that category, it's very diverse presentation. So somebody may present earlier in the disease process and may earlier in the age group with more severe peripheral vision loss and difficulties with night vision, to somebody who's gonna present later in their life with that specific, those specific issues.
So it's very diverse, but bottom line, you come down by grouping the patients into categories by having specific inclusion criteria that's gonna hopefully lead you to seeing that therapeutic window with the-
Mm-hmm
... with this modified therapy.
Thank you. And so, for patients, such as Mr. Fernandez, who are concerned-
003, please.
Zero.
0, 0, 3. Lucky 3.
So for patients such as zero, zero three, who may be concerned about passing on, you know, the disease to their progeny, so would therapies such as modified gene therapy be of help, or is it just personalized just for the patient alone?
Oh, no. No. I'm always worried about my kids, my grandkids. I was in the assumpt- assumption that with the fifth generation, it will stop, and that is wrong. Dr. Lam told me that. He taught me that. So I'm very worried about my family. Actually, at one point, I didn't want to have any kids because I didn't want this to happen to them. That's how bad it is. So yes, it's very important they being tested, all my two kids and my four grandkids, make sure that they don't have that development yet. And I hope they won't. And now, I know, I know it's not gonna happen to them, you know. Now I can see the light at the end of the tunnel. So, and, I'm committed to-...
Make awareness about it, because a lot of people may have the disease and may not progress, you know, a lot, because you cannot, I cannot, right here, I cannot see this here. So there's a lot of but I will not notice. You cannot notice. So it's very difficult for us to identify the illness. It's really, it's really sad that the only way we can do it is going through the doctor. And, you know, you, you guys were talking about outside the United States, not many people have the chance to go to an eye doctor, you know? And that's where probably the biggest problem, we may have more than the, the account that you have, the information that you have, so.
Thank you. So, Dr. Lam and Dr. Rasovic, as investigators, what attracted you towards OCU400, and how do you see this as a differentiated therapy that you wanted to start evaluating it?
So I think it's a very novel therapy because we have the traditional gene replacement therapy. Of course, we also have other things here under in the pipeline, like NAC and other type of treatments. But I think it's a first modifying therapy, and it can treat multiple genes, and it has a good scientific rationale. So it certainly makes sense that clinical trials should be conducted as well as we can to assess its clinical efficacy. I mean, I think we still, you know, are learning from it, and I think the design of the phase 3 clinical trial is really pretty robust because you have the arm for the rhodopsin mutation, and then you also have an arm that has the multiple genes.
So, I get attracted to clinical trials in any way that can help inherited retinal disease patients because, it's really our unmet need. I mean, it's a very progressive condition, slowly it sort of catches up with you, and it affects a person's whole well-being. So that's why I'm attracted to it. But specifically, you know, for clinical trials, we look at clinical trials with good basic science. We look at clinical trials which are feasible and which are novel, and, that's why we're doing the clinical trial.
To add to Dr. Lam, so I think all of us sitting here, because I'm thinking in general, eyesight is really important. I went into medicine, especially ophthalmology, 'cause I really wanted to enable people, you know, improving, saving that eyesight and enabling them to be really part of the society. And we underestimate how much that sense really is important in day-to-day function. So when I see a patient that gets the diagnosis of inherited retinal diseases, I will be honest, it's my least favorite diagnosis to make, because to date, I have... You know, I went into medicine with hopes to improve things. When I have a diagnosis where I can't make the change, I can help them function better, but not make it better or stop it, I'm not too thrilled with that, for certain.
So to have options or to participate in clinical trials, that we can change this for the patient, especially in more of a gene-agnostic approach, meaning, you know, delivering it for not just specific gene, but for multiple genes, multiple diagnosis, and potentially even for common retinal diseases, I think is very exciting. I think the novelty of that, and also the broader approach to helping many more patients, I think it's very exciting for me.
And then, Dr. Rasovic, as a surgeon, in terms of doing this surgery itself, how difficult is it? And in general, what's the learning curve? And once this gets approved by the FDA, you know, is that option by the surgeons, you know, a difficult one, or is it, you know, it can be done and it's easy?
Yeah. I mean, anytime we talk about surgeries, in particular, we always think about, gosh, that's an extra step. We're exposing patients to risks for certain, and we are. I mean, eye surgery is definitely a specialized field, one that takes lots of years of training. But I would tell you, as a retina surgeon, you know, the number one step that I do, or any surgery is the step that's being done in this surgery. So while it sounds like it's something, you know, unique, it really truly is not. Every retina surgery starts with removing the vitreous and kind of taking care of the back part of the eye. So the only additional step that's added to this is really delivering the drug underneath the retina, and, and that, I think, is also not quite challenging at all.
So to summarize it, I would say, yes, it's surgery. It definitely is, but we are delivering therapy in exact spot when it's needed. In the localized areas, we're minimizing exposure systemically to things, minimizing risk for the rest of the body, and delivering the therapy exactly where it's needed. So I would say it's just really one that every retina surgeon would be able to perform, something that they're already doing. The extra step is just adding that medicine underneath the retina.
Thank you. So, Dr. Lam, without going into specifics, we already heard the story of naught, naught three here. What has been the experience of some of your other patients, who are within that current trial right now?
... Well, I think, you know, in the phase one trial, we definitely have patients who responded, and some patients, of course, did not, and I think that was presented in the first part. So I think it's important to really, for phase three, to home in on those patients, which was in the presentation this morning, about how to choose patients that are really the best candidates for the treatment, right? Not for every disease, not all the patients are gonna, it's gonna be in the right criteria. So, I think the fact that we have a group of patients that have responded and that they also teach us about which endpoint that you're gonna choose for phase three, I think is terrific.
I think that experience is very valuable, especially in a phase I-IIa study, 'cause that's where you learn about safety as well as trying to find signals of efficacy. So I think you'll find the signal of efficacy, and I'm certainly glad that some of our patients did improve and the treatment was helpful. So I think that sort of propels you into the next phase, and you design it, and then you got a greater group where you have more criteria, and you have other primary endpoint and secondary endpoint. You choose them, and then they will help to determine the efficacy of the treatment.
So this is a question for both of you physicians. As you evaluate OCU400, and as the data starts come, you know, as the data gets read out, so what sort of clinical endpoints or clinical data you're looking for so that it can help not only yourselves but also your other colleagues to prescribe this drug? You know, is there something outside of the endpoints that you're really looking for in terms of quality of life or anything else?
Overall improvement in their functionality, and I think just, you know, hearing, you know, improvement in peripheral vision ability, that will translate to ability to drive in darker settings and, you know, more unfamiliar settings as well. To really, you know, your peripheral vision is very important to day-to-day function of you being able to get from this point to that point as well, and making sure that we're using that to identify the step as we're... So, you know, what I'm looking is, yes, I'm looking for individual acuity and kind of like the function in low light settings, their, you know, visual field in sense. But it would be nice, that very much translate to their ability to function in their day-to-day lives for certain, so.
So, I mean, that's well said. I think one, of course, is improvement in your vision, and that's why we want to capture it in endpoint tests, like the mobility test and so forth. We also want to learn from patients, like, what exactly they improve down, as well described here, because that allows us to know, for example, which aspect of vision truly improve, and I think that's very important. I think the other point that we want to know is that we may have patients that, say, didn't respond, and how do they, over time, maintain their vision and so forth. Of course, you know, that's helpful. And I think the safety profile is also important. That's why you need a larger group.
I mean, you will expose them to a new gene therapy with surgery, and, we want to know how many of the patients has inflammation and how many people have complications, you know? And pretty much like Luxturna, right? Luxturna went through phase 1, phase 3, and then they learned about all these aspects, and clearly, they had a good efficacy signal. So I think it's the whole package in any treatment so that you can understand all aspects.
So, in cell therapies in general and even including stem cell therapy, you know, the treatment needs to be done at the initial stages of the disease progression, you know, to be beneficial. As RP is a disease which progresses with age, is there a time point where you think OCU400 is most beneficial within the, you know, the progressive stage of the disease, or could this be beneficial at any time point?
I think that's exactly what we hope to find out from the clinical trials. I think that question particularly needs to be answered for future. I mean, ideally, we want therapy that we can use early on to not only stop disease progression, but have influence in improving things as well. So we hope that this will be the answer, or one of the answers. But I think that question is gonna be kind of teased out, I think, in trials.
So I think, I agree. I would just add that, clearly, you know, like any disease, you have people in different stages, right? So of course, people with milder disease, it's harder to prove efficacy. They have a ceiling effect. They're so good. I mean, how can you improve? So that is something that you don't enter those patients into a clinical trial, and subsequently, depending on the labeling of the product, that the FDA allows you to do, right? You know, 'cause you have patients who are really advanced, you know, in, let's say, their peripheral vision. Of course, at that point, you wonder if any treatment can help them, including optogenetics. So in those patients, you can't really test in phase 3, and that also will be dependent-
... what the FDA labeling is. If you look at Luxturna, I mean, Luxturna, actually, you have to have viable retina, and, but you also can treat patients as young as 1 years or older. So labeling of different treatment are very specific and, and very helpful. So that's, of course, something we will discover with phase 3, and then subsequently, I think the determination is what would be the labeling the product, and then when would the regulating agency, based on the data, would give in terms of the type of patients that will be treated. But, I think, you know, we certainly look forward to learning about all that, so.
Thank you. And in closing, Dr. Haider, so based on the clinical data that Ocugen has published today, hearing from the physicians and from 003, so what do you think now, from where you started and, what has been achieved to date? And, are there any gaps at this point that you think you know needs to get filled? And lastly, is modifier gene therapy something that can be used outside of eye, especially diseases like cancer, where there are multiple genes which interact before the disease gets manifested?
Three great questions. Let me address them one at a time. It is truly a full circle moment, to answer your question one. I sequenced chromosome 15 q22 and sequenced NR2E3, and then found the patients that had the disease mutations, and then developed the model and then the therapy, and then now I get to meet double O three. I can't express in words how profound that is to me to see this come to fruition. Many times, putting chairs together and sleeping in the lab, because we knew what an exciting and impactful science we were participating in. That's answer for question number one. Question two, regarding the clinicians and what they have said and how it can better inform, and the gaps in the space here.
So what I see, and actually, you gave a perfect segue to my next segue, is, the healthcare company. I'm starting Shifa Precision, because what's the next stage? Is helping the clinicians identify who would be the best. You're a product of your DNA and environment. When Dr. Lam was talking about those DNA points, that's points on your DNA for a modifier or a disease mutation. For us, when I was part of the genome project 20 years ago, and I think, "Why have we not harnessed this technology for health and wellness and diagnosis rather than recreational science?" We're changing that. We're going to do that. And so we're developing the biomarkers.
We're developing, actually, an integrative AI system that will give us personalized precision medicine, that will give us then precision therapies, so that they have better informed decisions, so they're not just left with when a patient comes in and what kind of physical diagnostic tools. Let's have molecular diagnostic tools also, so we can get to early diagnosis. So then, hopefully, my hope is we get past just this stage of reacting, which is amazing, and phenomenal will be when we get to prevention. When we can predict and then prevent, that will be beautiful for your grandchildren, for future generations to say, "You're not gonna have to worry about this, even if you have that, because you've got other options." And I think that then is to empower the clinicians.
The third answer, the impact, you brought up other diseases and, many of you, if you look me up online, you'll know the story. I'm a cancer survivor, actually, so near and dear to my heart, what you brought up. Again, maybe a, maybe a little part of impetus for Shifa, but yes, the impact of modifier therapy, the whole goal of that was thinking: How, when we have multiple roads to the same problem, how can we get to that root of the problem?
Mm-hmm.
How can we solve it, and how can we function and have a better quality of life in the context of everything on, in the inside molecular that we're thrown in with? I think what we're going to see, actually, is more therapies like this that are a modifier base, that are broad spectrum, that have this kind of broader impact and effect. You partner that with precision medicine, precision therapies, then you'll get to personalized medicine, then you'll get to personal wellness and optimal wellness for each of us. I think this is a platform and amazing partnership with Ocugen that has brought this to the forefront, and that we see the potential and value of it, but it doesn't stay just within a retina-
Mm-hmm.
or an ocular surface. This actually can be impactful. I think the future of therapies may actually even be combination therapies. You know, maybe a follow-up to the Spark Luxturna will be put in OCU400, and then you might have an even more robust effect, for example. However, that's where I see the future is going to go-
Thank you.
-in therapeutics.
Thank you very much. We have a clear lead?
Great. That's a great panel. Thank you so much, Dr. Lam, Dr. Lejla, Mr. 003. And, Neena. It is incredible. I mean, this is what, you know, we do every day, and thanks to all the investigators, patients, and the consultants, our scientific advisory board members, and foremost, my... You know, all our staff at Ocugen, they work day and night, and you saw Arun, Huma, and others. They work so hard for that purpose, and we believe in. We can help these patients. They should not be left, you know, thinking there's no rescue for them. And we are the hope. We are going to continue to work hard, and we're going to get this hope, actually get it to more patients. So your grandkids, Mr. 003, can have a hope, right?
Thank you.
And so they can prevent it. Thank you so much. It's incredible, incredible journey, and we all learned a lot from you, and that's what we do, what we do. And you're actually exciting us and motivating us more.
Yeah.
Yes.
Thank you so much. Thank you all for attending today.