Good morning and welcome to Ocugen's webcast to discuss data from the first half of patients completing one year since treatment in the OCU410 phase II ArMaDa clinical trial for geographic atrophy. Please note that this call is being recorded at this time. All participant lines are in a listen-only mode. Following the speaker's commentary, there will be a question-and-answer session. Joining on today's webcast are Dr. Shankar Musunuri, Chairman, CEO, and Co-founder, Dr. Huma Qamar, Chief Medical Officer, and Dr. Arun Upadhyay, Chief Scientific Officer, along with distinguished clinical trial investigators: Dr. Jay Chablani, Dr. Arshad Khanani, and Dr. Lejla Vajzovic. As this webcast is being recorded, a replay with the accompanying slide presentation will be available on the website. Thank you. Thank you, Operator. Good morning and thank you for joining this important update on our OCU410 program. Today's presentation will focus on clinical updates from the phase II ArMaDa trial, along with some new data from phase I. This presentation contains forward-looking statements regarding OCU410's clinical development, regulatory timeline, and therapeutic potential for geographic atrophy. These forward-looking statements are subject to significant risks and uncertainties. We have assembled an exceptional group of clinical and scientific leaders to walk you through every aspect of our program. Dr. Arun Upadhyay, our Chief Scientific Officer, will dive deep into OCU410's novel mechanism of action, how RORA modulation addresses multiple pathways implicated in GA progression. Dr. Huma Qamar, Chief Medical Officer, will outline our comprehensive clinical development plan, including the rationale for our regulatory strategy. Dr. Jay Chablani from the University of Pittsburgh and UPMC Vision Institute, and President of NetraMind, will present phase I ArMaDa trial data updates. Dr. Lejla Vajzovic, Duke University, will discuss the phase II interim results, highlighting efficacy and safety findings. Finally, Dr. Arshad Khanani from the University of Nevada, Reno and Sierra Eye Associates will join his colleagues for the Q&A. I'd like to set the clinical context for today's discussion by reviewing the unmet medical need in geographic atrophy. Geographic atrophy, or GA, is an advanced form of dry age-related macular degeneration. GA is characterized by progressive, irreversible degeneration of the retina and retinal pigment epithelial cells in the macula, the central portion of the retina critical for detailed vision. This process leads to irreversible loss of central vision, with patients experiencing progressive scotomas that coalesce and expand over time. Currently, two to three million patients in the combined U.S. and European markets suffer from GA. This represents an enormous population of visually disabled individuals with limited therapeutic options in the U.S. and no therapeutic options outside of the U.S. Until very recently, there were no approved treatments for GA. Just in the last few years, two therapies have been approved: Syfovre and Izervay. Combined, these represent over $1 billion in combined U.S. annual sales, underscoring the significant unmet medical need and market opportunity. However, these approved therapies have significant limitations. Most critically, they each address only one of the four major pathways implicated in GA disease progression. Additionally, both require frequent intravitreal injections, six to 12 times per year. These injections carry cumulative risks, including endophthalmitis, retinal detachment, inflammation, and other serious complications. Patients must commit to lifelong monthly or bi-monthly office visits for injection administration. This is where OCU410 represents a paradigm shift. OCU410 is designed to address all four pathways associated with GA through a single subretinal injection of an AAV5-delivered RORA gene therapy. As a one-time administration that potentially provides durable benefit, OCU410 offers GA patients an unprecedented opportunity for comprehensive disease modification without the burden of chronic injections. We are executing well on our ambitious development pathway for OCU410. You will hear more about data from approximately 50% of patients in the phase II clinical trial at one year today. We'll provide a full data set later this quarter. We also plan to initiate our phase III pivotal trial later this year. In 2027, we target completion of phase III enrollment, allowing us to begin our follow-up and final analysis. OCU410 phase II clinical trial. In 2028, we anticipate generating top-line phase III data and submitting our Biologics Application, or BLA, to the FDA. Now, I will hand it over to Arun. Arun. Thank you, Shankar. And I will now walk you through the scientific rationale for OCU410 design and its multi-pathway mechanism of action. OCU410 utilizes a modified therapeutic approach targeting RORA, the retinoid-related orphan receptor alpha. RORA is a nuclear receptor that functions as a master regulator of multiple homeostatic pathways in retinal cells, particularly in the retinal pigment epithelium and photoreceptors. Our preclinical research has demonstrated that OCU410 provides four distinct therapeutic benefits. First, anti-drusen activity. In the model of macular degeneration, we have shown that RORA activation leads to reduced drusen burden and improved overall retinal architecture. This is significant because drusen accumulation is a hallmark of AMD progression and is thought to contribute to RPE dysfunction and photoreceptor death. By reducing drusen and supporting RP health, OCU410 addresses a fundamental aspect of GA pathogenesis. Second, anti-oxidative protection. Oxidative stress is a major driver of both RPE and photoreceptor cell death in GA. In cell survival assay using ARPE-19 cells, which is like representative of human RPE cells, RORA overexpression provides robust dose-dependent neuroprotection against oxidative stress. This indicates that OCU410 can enhance the intrinsic antioxidant defenses of retinal cells. Third, anti-inflammatory modulation. GA progression involves microglial activation and local retinal inflammation that exacerbates photoreceptor loss. In microglial cell model, RORA expression suppresses pro-inflammatory cytokines and chemokines, effectively inhibiting this harmful inflammatory cascade. By reducing neuroinflammation, OCU410 protects photoreceptors from immune-mediated injury. And fourth, anti-complement activity. Complement system activation has recently emerged as a critical mechanism in GA pathogenesis. RORA upregulates CD59, an important complement regulatory protein that protects photoreceptors and RPE from membrane attack complex formation. This prevents complement-mediated cell death, another key pathway in GA progression. What makes OCU410 particularly innovative is that it targets these four convergent pathways with a single therapeutic intervention. Rather than blocking one mechanism, as the existing approved therapies do, OCU410 simultaneously addresses multiple critical disease mechanisms. This multi-pathway approach has the potential to provide more robust and potentially more durable therapeutic benefit. Now to Huma. Huma. Thank you, Arun. The phase I ArMaDa trial was conducted as an open-label dose-escalation dose-ranging study designed primarily to assess the safety and tolerability of OCU410 in patients with geographic atrophy secondary to dry age-related macular degeneration. The trial enrolled a carefully selected patient population with documented GA, and we implemented a rigorous dose-escalation protocol with formal safety monitoring at each stage. The dose-escalation schema utilized a 1:1:1 randomization and included three cohorts. The low-dose group received 2.5 × 10^9 VG per mL in 200 μL. The medium-dose group received 5 × 10^10 VG per mL in 200 μL, and the high-dose group received 1.5 × 10^11 VG per mL in 200 μL. Each cohort consisted of three patients. Importantly, after treating each dose cohort, we convened our data and safety monitoring board for formal safety review at four weeks post-injection before proceeding with dose escalation. This rigorous DSMB-monitored approach ensured that we identified any safety signals early. For primary endpoints, we assessed safety and tolerability through adverse event monitoring, serious adverse event tracking, and intraocular pressure measurements. Secondary endpoints included structural assessment via indirect ophthalmoscopy and fundus autofluorescence imaging to detect any retinal changes. We also included several exploratory endpoints designed to generate preliminary efficacy signals. These included quantification of drusen volume using spectral domain OCT, careful monitoring for conversion to wet AMD, microperimetry testing using the MAIA device to assess retinal sensitivity, patient-reported visual function using the NEI Visual Function Questionnaire 25, and comprehensive immunological monitoring, including humoral and cellular immune responses, as well as viral vector shedding analysis. We did not exclude patients with CNV, choroidal neovascularization, in the fellow eye. This allowed us to treat a broader patient population while maintaining rigorous monitoring for treatment-related exacerbation of wet AMD. I will now turn the call over to Dr. Jay Chablani, one of our clinical trial investigators, who will review the safety and efficacy updates from phase I portion of the study. Thank you, Huma. OCU410 phase I enrolled nine elderly AMD patients with asymmetric disease. Study eye 47 letters VCVA versus fellow eye 68 letters with a baseline lesion size ranging between 7.7-8.2 square, choosing the eye with worse visual acuity to receive treatment. No cases of ischemic optic neuropathy, vasculitis, endophthalmitis, or choroidal neovascularization were observed, representing a relatively safe and tolerable profile for OCU410 among the doses tested. This favorable safety and absence of serious inflammatory or ischemic complications support advancement to phase II with dose escalation and expansion studies to study efficacy. OCU410 treatment demonstrated a 20.2% reduction in geographic atrophy lesion growth at 12 months compared to untreated fellow eyes. This intrapatient comparison leverages the asymmetric disease model as an internal control, excluding three subjects: two with foveal detachment during surgery, one high-dose patient with loss to follow-up, and this helped us to determine the treatment effect. The 20.2% relative reduction in lesion progression rate represents a meaningful early efficacy signal suggesting OCU410 slows GA progression. The most striking finding from phase I trial is the preservation of photoreceptor structure in treated eyes as measured by spectral domain OCT. At 12 months of follow-up, we observed OCU410 treated eyes demonstrated 60% slower loss of the ellipsoid zone, which is a structural exploratory endpoint for the study, ellipsoid zone compared to untreated fellow eyes. The EZ, that is ellipsoid zone, represents the inner segment-outer segment junction of photoreceptors as visualized on spectral domain OCT imaging. This is a critical anatomical marker of photoreceptor health and integrity, and loss of ellipsoid zone indicates photoreceptor degeneration and death. Preservation of the ellipsoid zone indicates maintained photoreceptor structures and, by extension, likely maintained or improved photoreceptor function. The 60% reduction in EZ loss rate indicates that OCU410 treatment is substantially slowing the rate of photoreceptor degeneration compared to the natural history observed in the untreated fellow eye of the same patient. This is consistent with our preclinical findings regarding RORA's neuroprotective and antioxidative mechanisms, and it provides the first clinical evidence that OCU410 can preserve photoreceptor structure in GA patients. Building on our ellipsoid zone findings, we extended our analysis to examine the broader EZ-RPE complex, a composite measure that includes both the photoreceptor layer and the underlying RPE. The EZ-RPE complex represents the functional unit of photoreceptor-RPE interaction. Loss of this complex indicates degeneration of both photoreceptors and the supporting RPE layer. Preservation of EZ-RPE complex, therefore, suggests that OCU410 is protecting both retinal layers simultaneously. Our analysis demonstrated OCU410 treatment resulted in reduced loss of EZ-RPE complex at 12 months post-treatment compared to untreated fellow eyes, indicating a treatment effect on both the photoreceptor and RPE compartments. This finding is particularly significant because it suggests that RORA modulation is working at multiple levels within the retina. We see photoreceptor protection consistent with our antioxidative mechanism. The ability to protect both photoreceptors and the RPE with a single therapeutic intervention underscores the advantage of multi-pathway targeting approaches. We are now not just addressing one aspect of GA pathogenesis. We are supporting the health and survival of the entire photoreceptor-RPE unit. These structural findings provided compelling rationale for advancing to phase II with controlled efficacy endpoints in a larger patient population. Now, back over to Dr. Huma Qamar. Having established the safety profile and observed promising structural preservation signals in phase I, we advanced to phase II to assess OCU410's efficacy in slowing GA progression. The phase II trial employed a randomized control design with 1:1:1 randomization, enrolling a total of 51 patients across three groups: high dose, medium dose, and an actual control. The control group, medium dose, and high dose treatment group all included 17 patients. The control group received no treatment. The medium dose included 17 patients who received 5 × 10^10 VG per mL in 200 μL, and the high dose treatment group included 17 patients who received 1.5 × 10^11 VG per mL per eye in 200 μL. Safety monitoring remained rigorous with data and safety monitoring board reviews conducted at four weeks post-injection for both initial and subsequent cohorts. A primary efficacy endpoint was change in GA lesion size quantified in square millimeters using fundus autofluorescence imaging. The change in lesion size from baseline to 12 months represents a direct measure of disease progression or stabilization. The rationale for lesion size as the primary endpoint is well established in ophthalmology. GA lesion size measured by FAF correlates strongly with functional decline and visual disability. This endpoint has been adopted by regulatory agencies for GA trials. Secondary efficacy endpoints included change in low luminance visual acuity, a functional measure of vision from baseline at 12 months. I will now pass the call to Dr. Lejla Vajzovic. Thank you, Huma. OCU410 phase II enrolled 51 elderly age-related macular degeneration patients with mean age 75.9 years, with the treated eyes averaging 55.1 letters in best-corrected visual acuity, 30.32 ETDRS letters in low luminance visual acuity, and lesion size of 8.03 sq mm, with patients from early to late-stage geographic atrophy suitable for tracking disease progression enrolled. OCU410 demonstrated a clean safety profile with no choroidal neovascularization, retinal vasculitis, intraocular inflammation, or serious to severe adverse events. Differentiated program from monthly and every other month injections competitors that may experience CNVM, vasculitis, intraocular inflammation, serious and severe events. As a single administration of gene therapy, OCU410 eliminates the ongoing cumulative injection-related risks that patients on approved therapies experience every month or other month basis. The potential therapeutic effect of OCU410 is expected to be durable in lifetime and one-and-done treatment. This represents a paradigm shift in geographic atrophy management from chronic injection-dependent therapy to durable disease modifications. At 12 months, OCU410 treatment resulted in 46% statistically significant reduction in GA lesion growth in treated eyes compared to control eyes, and the P-value was 0.015. The analysis included 23 eyes, five control eyes, 18 eyes in treatment group, of which 10 treated eyes received medium dose and eight eyes received high dose. For this analysis, the medium and high-dose treated groups were combined, as you can see. This population included both patients with foveal involving and subfoveal atrophy patients. The P-value of 0.015 provides a robust statistical support for the treatment effect, indicating the observed benefit is significant. Currently, a 46% reduction in lesion growth rate means OCU410 treated patients are experiencing slower expansion of the atrophic lesions. This translates to delayed central vision loss and maintenance of useful vision for a longer period. With the phase II treated population, we examined lesion size reduction separately for the medium and high-dose groups, as the data on the left shows. The medium dose group demonstrated a 54% reduction in lesion growth compared to control. The high-dose group demonstrated 36% reduction in lesion growth compared to control. This data reveals an important dose-response relationship, but not the relationship one might initially expect. The medium dose appears to be providing better efficacy compared to high dose. This finding warrants careful interpretation. Several factors could explain why high dose appears less efficacious. First, there may have been baseline imbalances between the medium and high-dose groups. For example, high-dose groups may have had slightly larger or more aggressive lesions at baseline. Second, the high-dose group has fewer evaluated patients, limiting statistical power. Third, and perhaps most intriguing, there could be biological factors related to excessive transgene expression, what we call a plateau effect, where the additional vector doesn't provide additional benefit. Both of those groups show statistically significant improvement versus control with medium dose with a P-value of 0.02 and high dose with a P-value of 0.05, but numerically superior to the medium dose is clear. We are looking forward to presenting the complete findings for all subjects enrolled post-data lock analyses. The right panel shows a subgroup analysis of patients with baseline GA size equal or greater than 7.5 sq. These are patients with more advanced atrophy. In this subgroup, OCU410 demonstrates a 57% reduction in lesion growth and a 14% compared to controlled eyes. This 57% reduction in lesion size suggests that OCU410 may be more effective in patients with substantial disease burden, exactly the population we want to treat. In addition, both medium and high-dose OCU410 were equally effective in decreasing the lesion size in patients with large lesion size. I want to now compare OCU410's efficacy in a broader clinical context by comparing our results to currently approved therapies. OCU410 at 12 months demonstrates 46% reduction in lesion growth compared to control. This represents our interim primary efficacy analysis in this phase II. For comparison, published data on approved therapies, specifically Izervay, specifically looking at OAKS and DERBY trials. The published data by Jaffe et al. in 2023 shows approximately 22% reduction in lesion growth at 24 months. I would like to emphasize that there has been no head-to-head trials that have been compared or conducted between OCU410 and approved therapies. The direct comparison is clearly limited, but we're comparing the phase II assessor-blind and controlled study to published trials with different patient population, trial designs, follow-up periods as well, and that said, there seems to be a clear contrasting difference. OCU410's 46% reduction at 12 months compared to 22% approved therapies at 24 months suggests a potentially greater and even twofold therapeutic advantage through this. Interpretation should be very much taken cautiously with acknowledgment of different trial contexts. We also examined response rates, the proportion of patients achieving clinically meaningful benefit. OCU410 demonstrates significant response rates with up to 50% of treated patients achieving greater than 50% lesion size reduction compared to control at 12 months. This response rate analysis provides perhaps the most compelling evidence of OCU410's clinical value. A therapy that provides substantial benefit of half of treated patients represents a transformative advance for populations facing otherwise relentless disease progression. I will now turn the call over to Dr. Huma Qamar to summarize the clinical updates. Thank you, Lejla. In conclusion, the evidence presented above supports OCU410 as a transformative therapy for geographic atrophy. First, OCU410 employs a comprehensive multi-pathway mechanism of action. Unlike approved therapies that target a single pathway, OCU410 modulates RORA to activate multiple protective pathways simultaneously. The unique four-way mechanism of action has been rigorously validated in preclinical models and supported by clinical efficacy data. Second, OCU410 demonstrates compelling clinical efficacy data: 46% reduction in lesion growth at 12 months compared to control, 57% reduction in lesion growth at 12 months compared to control in patients with larger lesion size greater than or equal to 7.5 sq at baseline. Up to 50% of patients achieve greater than 50% lesion size reduction compared to control. And third, OCU410 has established a very favorable safety and tolerability profile. No serious adverse events related to OCU410 have been reported to date. Fourth, OCU410 addresses a massive unmet medical need with significant market potential and estimated two to three million GA patients in the U.S. and E.U. with limited treatment options and potential of one-time definitive treatment versus a lifetime of monthly or bi-monthly injections for approved therapies and multi-pathway targeting mechanism offering potential for more durable and comprehensive disease modification. Before I open up the Q&A, I would like to ask Dr. Arshad Khanani a question based on what we have all seen today. What are your thoughts on the OCU410 data and how do you see it fitting into your clinical practice? Thank you, Huma. Good morning, everybody. Congratulations to you, Shankar and the Ocugen team for this data set. You know, I've been involved with numerous programs for the development of treatment of geographic atrophy, and we are lucky to have, obviously, the two approved treatments. But as highlighted, there are several things that are important to consider here, and this program addresses unmet needs. When I'm looking at the data from phase I, phase II, obviously, this is a one-time gene therapy. The biggest burden we have for our patients in clinic is the treatment burden of injections every month and every other month. And as we start those treatments, over time, there's a very high dropout for patients. And of course, each injection brings a risk of, you know, endophthalmitis and other things, including CNV. So we are lucky to have treatments, but the next generation of treatments for geographic atrophy, we have to address several unmet needs. And I think when I look at this program, I'm looking at, number one, safety. When it's a one-time gene therapy, we need to make sure it's safe. We have not seen any safety signals here. And as we know, subretinal gene therapy obviously does not cause immune responses. And I'm happy to see that we have not seen any intraocular inflammation, any endophthalmitis, or any vasculitis. Number two is efficacy signal. You have a consistent efficacy signal that you can see in phase II and, of course, the interim analysis from the phase II. So that is very important. And of course, I'm very excited about the ellipsoid zone data that was presented by Dr. Vajzovic. I think that is an important endpoint that is now utilized by many programs as a primary endpoint. So overall, when I look at this data set, I'm seeing, you know, the things I would like to see in phase I and phase II is no safety signals, efficacy that is consistent. So I'm excited to see the full data set from phase II and very excited to see the program that will move forward, and I'll be enrolling patients, obviously, in the phase III program. And in terms of the unmet needs, I think a one-time gene therapy for GA will be widely adopted because these are patients that have very difficulty coming in every month and every other month. And then, of course, many of these patients have bilateral disease. Great. Thank you so much, Dr. Khanani. And now, operator, please open up the call for questions. Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. If you are called upon to ask your question and are listening via speakerphone in your device, please pick up your handset to ensure that your phone is not on mute when asking your question. Again, press star one to join the queue. And our first question comes from the line of Robert LeBoyer with Noble Capital Markets. Your line is open. Good morning. Congratulations on all the data, and thank all of you for those comprehensive discussions and explanations about the mechanism and the data. One of my questions has to do with the EZ zone, and I was hoping you could give a quick review of the biology there, the effects you've seen, and the significance, and perhaps if any of the approved drugs have that similar type of effect. Dr. Jay Chablani, the question is for you. Thanks, Huma. Hi, this is Jay Chablani. I am a retina specialist. I have been involved in the analysis of this particular structure, and I have a keen interest in the outer retinal structure, so ellipsoid zone actually represents the key anatomical biomarker of the photoreceptor cells, and photoreceptor cells are the one which pretty much does the most of the job to, you know, save the vision, so luckily, with our high-resolution imaging, now we are able to see this structure, and OCT gives us almost a histological view of the retina, and so this structure has been evaluated in many diseases, primarily on macular degeneration, because, you know, the available treatment options have been focused on saving the vision or delaying the progression, but this structure has not been evaluated in any of the trials earlier. Though some post-hoc analysis has been done, but I really admire the Ocugen team that they are looking at this structure rarely in the clinical trial, and we are seeing really fantastic results in phase I, and we are looking forward to the phase II as well as phase III in this analysis. So overall, I would say that this is a structure which has been used for approval for the recent implant for macular telangiectasia, which is a different disease than macular degeneration. So it looks like the FDA is very much open for accepting this as an anatomical outcome measure, which will certainly change the way we are looking at the clinical trials and definitely help us to improve our outcomes. One more thing I'll add is that the recent studies which we are doing, they are also showing that this structure is related or correlated with functional vision as well, which again is something which the FDA wants as a functional vision outcome as well. So I think that this will become a very important clinical biomarker. Okay. Thank you. That's very helpful. And I also had a question. I agree. This is very interesting data, and I'm also looking forward to more of it. Could someone lay out some of the milestones or expected timeframes for additional data? Yes, I can answer that. So we are anticipating our full data set towards the end of the quarter, and we are also looking at the phase II full study report at that time. So we will be sharing the information accordingly, as we also anticipate phase III initiation in 2026 as well. And the phase II data will also be pivotal in terms of defining our strategy for phase III in 2026. Okay. Great. Thank you very much for that. I'll jump back in the queue and let others ask questions. Our next question comes from the line of Elemer Piros with Lucid Capital Markets. Your line is open. Yes. Good morning. Congratulations. What I'd like to ask is if you have any idea which dose would you take forward into a pivotal trial? That's my first question. And perhaps to Dr. Khanani or some of the other experts. In a pivotal trial, would you recommend to restrict the population to a certain lesion size or stage of the disease, or would you recommend to examine the entire population without restrictions? Yes. So in terms of your first question in terms of the dose, we are currently evaluating both the doses, medium dose and high dose, as the study is not closed yet. Once the data set is available for phase II and we close the study, that will be the point that we will be carefully analyzing the data and coming up with the efficacious dose for phase III. And for the other question, I would let either Dr. Khanani or Dr. Lejla Vajzovic to answer that question. Thank you, Huma. I can take that, and then I'm sure Lejla will follow up, so those are great questions. So I think, you know, when you're designing the phase III program, you use the full data set from phase II to kind of evaluate the efficacy signal, and then you tease out the population that will have the highest benefit, so here, obviously, we are looking at an all-comer patient population, but I think I'm looking forward to the full data set, and then after that, we'll be able to evaluate, you know, which patient population will be the right one. But in general, yes, we do limit the size of the GA lesion, very similar to the GATHER2 program or Derby and Oaks program, on average, you know, 7 mm sq- 8 mm sq, but of course, you have patients with small lesion and larger lesion. As you know, some programs have all-comer patient population, like we have here, where you have foveal and non-center point involving patients, while others like GATHER2, we only had non-center point involved patients. So I think those are really, really good questions, and I think we'll be able to refine those criteria after we have the full data set. But the way we are looking at this data set, this analysis, clearly, these interim results clearly show that there's a benefit that appears to be on average in most patients, which is actually very good news. But I think once we have the full data set, we'll tease that out for you. Lejla, anything from you? Yeah. Thank you. Thank you, Arshad. Now, said really beautifully. Just to add and to point out, I think it's exciting to see such positive results this early for such a, you know, in general, progressive, relentless disease. I similarly look forward to seeing the complete data set to help us really educate ourselves how to move forward with the phase III in terms of what dose and also baseline characteristics for the patient's role. But in this diverse patient population with foveal and extrafoveal lesions included, I think it's exciting to see results in both doses. Perhaps just a little follow-up. Since OCU410 addresses the complement pathway, would there be a necessity to follow up with currently existing treatments down in the future once approved? So I will direct this question to either of our QAs. Arshad, do you want to take that? Yeah. Can you rephrase that? Are you asking about that the comparator will have to be an approved treatment? Is that the question? No. Just think, I mean, in the future, once OCU410 is approved, is there a rationale to further treat once the gene therapy is applied with complement inhibitors, currently approved drugs, since OCU410 already addresses the complement pathway? Yeah. That's a very good question. I mean, I think the efficacy we are seeing, you know, with this program is in line or superior based on, you know, phase I or phase II interim data compared to what we have currently. So I think the goal here is that this will be a one-time gene therapy that will obviously deliver similar efficacy or better efficacy without the burden of injection. So I don't think at this stage, I would think that we will need to add complement inhibitors on top after giving this to patients. But obviously, you know, real world, many different things happen. But I think the hope here is that we'll be able to decrease the treatment burden for our patients significantly with this one-time gene therapy modulating complement pathway and, of course, other pathways, as you saw earlier. Thank you very much. Next question comes from the line of Ramakanth Swayampakula with H.C. Wainwright. Your line is open. Thank you. Thanks, Ocugen team, for doing this for us this morning. A couple of quick questions. So for the physicians online, you were stating that, you know, with the current therapies, it could potentially become burdensome, that adoption with the potential with the current therapies could wean off over time. So when 410 comes to the market, you know, would you consider this as the first therapy for a patient who comes in with this indication, or would you wait to see how patients react to the currently approved therapies before giving the gene therapy? And I'm just trying to figure out, is there going to be a sequencing thing, or you really don't need sequencing based on the safety and efficacy that you're seeing with 410? Happy to take that. Lejla or Arshad, do you want to take that? Yeah. Lejla or Arshad? Yeah, happy to take it on. And currently, with geographic atrophy, patients often come in with, unfortunately, visual acuity affected, at least to a retina specialist's office. So I think time is critical to kind of help them preserve the vision and continue to stay active in their day-to-day activities. And for that reason, I most certainly would want to offer more durable and one-time approach. Now, the current therapies that are approved, we use on a monthly or bi-monthly basis. And while we know they're efficacious in clinical trial settings, we don't have the best way of following or assessing how this particular patient is responding to therapy. So we are treating the patients knowing our results from clinical trials show, you know, up to 22% of reduction over time, but the current real world doesn't have the best way to follow these patients and respond. And there's much work being done to change this. Lots of software analysis from various companies are, you know, underway and most likely will be available in the future, but not currently. And then to kind of summarize my answer, I would love to kind of just start with an approach that solves it, so to speak, for the patient, and it provides a durable option. Once the disease is diagnosed, then we most certainly see visual acuity affected. Yeah. And I would like to add to what Lejla was saying is that, you know, I'm a treater. I use complement inhibitors in my practice, and I'm implementing them earlier and earlier to preserve, you know, central function and then to slow down the growth of the lesions. But what is the hope that I give to my patients that come in? I say, "This is the first generation of treatments. We are lucky to have them, but we have other treatments coming down the pipeline." And in the future, just like what happened with wet AMD, you know, we went from PDT to anti-VEGF, and then we went from monthly anti-VEGF to bi-monthly, and then every three to four months, and then now we're looking at possible six months with TKI. So what I'm telling my patients is that, you know, we have more durable treatments coming in. Let's hold as much retinal tissue saved as I can now. So I think the biggest population right away, once, you know, 410 is approved, would be the patients who are already treated with complement inhibitors. And if we show efficacy, as I said, similar or close enough or even better, which I would be very happy with, then those patients that are already established will be very interested in getting gene therapy because they'll be on injections for a while. Now, obviously, not every patient can get gene therapy because we have to go to the operating room, but I think the majority of the patients can. So I think the established market definitely will be right there for us to help so that we can reduce the treatment burden. So, just to add to what Lejla said, everything else in terms of, you know, gauging the benefit, and I totally agree with Lejla. Thank you very much for that. Huma, I just have a second, you know, two-part question. This is on the responder rate. So you had seen a 57% reduction in baseline lesions. Does OCU410 modify the mechanism? Does it require a certain existing level of disease activity, you know, to show a maximum effect? And also on the 50% responder rate, did you get to characterize the non-responders, you know, in terms of either genetic markers or baseline, you know, inflammatory profiles or any such thing that could help us understand why we are not seeing as much response as the ones that responded? No, the answer is no and no to both, and there is the inclusion. If you look at the inclusion-exclusion criteria of our protocol, it has been very consistent with 2.5 mm sq-21.5 mm sq up to 80 scales, and it's pretty much consistent with all the, you know, products that have been approved. And also, geographic atrophy is the last stage of the dry age-related macular degeneration. We also had foveal and parafoveal lesions too. But in terms of the markers and, you know, the response rates, at this point, we are only mentioning different reduction across different, you know, combined dose groups as well, which is great. Also, if you look at that, there was a greater reduction observed in subjects with greater than 7 or equal to 7.5 mm sq at baseline as well. This is all preliminary interim analysis that we are looking into. We will have more information as to what we do with the actual control that we have. But to your question, it's no and no to both. Arun, do you want to add something to it? No. I think we're good. Okay. You're good? All right. Yes. So our case. Thank you. Thank you for taking all my questions. Sure. Again, if you would like to ask a question, press star, then the number one on your telephone keypad. We have a question from Michael Okunewitch with Maxim Group. Your line is open. Hi there. Thank you for taking my questions this morning. Congratulations on the progress. Thank you. I would just like to see if you'd comment a little bit on the importance of some of the different measures you used, in particular, ellipsoid zone loss versus lesion growth, and how these might differently translate into a patient's visual outcomes. Yes. So I would direct this question to Dr. Jay Chablani. Thanks, Huma. So I would say that, you know, ellipsoid zone is a very critical structural biomarker, which now we are able to see on OCT scans. And this biomarker has been shown to be related to the functional vision as well. So we have been looking at this biomarker for now for quite some time, and I think that this is one of the first trials who is looking at this biomarker at a very early stage of the clinical trial. So ellipsoid zone becomes very critical in regards to the retinal sensitivity, which has been shown to be related, which has been shown on microperimetry, as well as related to the contrast sensitivity. So I think that this will certainly become a very important anatomical biomarker on OCT. The other trials are, I would say, the other trials or other drugs which have been approved. They have used fundus autofluorescence, which is definitely one of the very important imaging which we use in our clinic. But considering that fundus autofluorescence does not give us a depth-resolved information, which we get from OCT, so therefore we prefer to look at the ellipsoid zone over fundus autofluorescence imaging. Arshad, do you want to add anything to it? Yeah, definitely. I think it's a great question, and I would say that ellipsoid zone is becoming an important biomarker, as Jay was saying. And, you know, we actually had ellipsoid zone in Delphi panel, and I presented the data at AAO, where we actually have a steering committee, which I'm part of, and we have world-renowned experts who are part of the panel. And I think it's consistent that ellipsoid zone is going to be the primary endpoint in many trials. I think one paper I want to direct you to is the ReCLAIM-2 paper. You know, of course, Justis Ehlers at Cleveland Clinic, who's a good friend, has led the work for ellipsoid zone. He was also the one that actually helped Stealth get ellipsoid zone as a primary endpoint for their phase III trials. When you look at the ReCLAIM-2 data, there was a reduction in ellipsoid zone attenuation or loss, and it was also associated with 10-letter greater gain in LLVA or low-luminance BCVA versus placebo. So I recommend, if you want to read more about it, please read that paper. But the bottom line is that ellipsoid zone will be something that most companies will be using as a primary endpoint in the future because, as Dr. Chablani said, it's more associated with the functional benefit. Yeah. Thank you. And if I may just add, like, it was very well described by my colleagues. We're also seeing this important structure not just be of great value in geographic atrophy, but other macular diseases. So one of the, you know, approved therapies now for rare condition for MacTel Type 2, and Stealth was approved based on exactly this: the anatomic measurement of EZ changes over time. So clearly, there's a landscape shift in our specialty from looking at best corrected visual acuity, looking at the primary endpoint for our trials, but really looking at anatomic features of the OCT to help us really see the changes, which do translate to changes in function for the patient as well. Thank you. And then I just would like to see if you could help me understand the decision to select 50% lesion size reduction versus control as the threshold for the responder analysis. Is that the meaningful threshold, or could something less like 20% still be significantly meaningful for these patients? So if you're making a decision on the path, yes, so if you look at approved therapy, and with just like, you know, around 20%, you know, reduction in lesion growth has been the basis for approval. So we just wanted to look at our interim data, you know, setting various cutoffs and see how this patient population is responding. So it is not that we need to have a 50% to demonstrate significance, but what we are highlighting is that with this therapy, even close to 50% patients, you know, subjects are responding more than 50% reduction in lesion growth, which is really remarkable and compelling at this stage. So we can think of this as a very high target to set. Yeah. Anything from a clinical perspective, if I may add, we are talking about differences between monthly or bi-monthly injections for our patients, elderly patients, versus potentially doing a one-and-done approach. I think that has to be taken into context as well because the treatment burden on getting monthly or bi-monthly injections, especially at that age group, is quite troubling, and most patients can't keep up with such a frequent injection volume. Yeah, I agree. And I think the key is, as a clinician, if you have an approved gene therapy, even if it is less efficacious than approved treatments, let's say it is 18 or 15, obviously, we are seeing better here, but I think it brings value. A one-time procedure, as highlighted by Lejla, is something we have to keep in mind that that will bring so much value to the patients, even if the efficacy is slightly less than approved treatments. I think it still will be adopted because of the treatment burden issue that we face with our patients. We also have many patients with wet AMD that are needing treatments that also have geographic atrophy. If you look at real-world studies, you know, overall GA patient population, 30%-40% of patients that are being treated for wet AMD also are getting anti-complements. I mean, 30%-40% of patients who are treated with anti-complements have concurrent wet AMD. So having a one-time treatment to relieve burden for these patients that have even more burden will be very important and very well accepted by the patients as well as the physicians. Thank you very much for taking my questions. This concludes the Q&A portion. I will now turn the call back over to the Chairman, CEO, and Co-founder, Dr. Shankar Musunuri. Thank you. Looking forward, our regulatory path is clear. We anticipate phase III initiation in 2026 using the safe and efficacious dose as established from Phase II ArMaDa trial post-data base lock. With successful phase II outcomes, OCU410 has the potential to become a paradigm-shifting therapy for geographic atrophy, offering GA patients a durable, well-tolerated, one-time gene therapy that comprehensively addresses the multiple pathways driving disease progression. Thank you for joining us, and have a great day. Ladies and gentlemen, that concludes today's call. Thank you all for joining, and you may now disconnect.