Good afternoon, and thank you for joining the H.C. Wainwright Sixth Annual Ophthalmology Virtual Conference. For this panel discussion, I'd like to welcome the following panelists to share with us their view on the novel therapies for inherited retinal disorders, including Stargardt disease and retinitis pigmentosa that could potentially enter the market in 2027. We have Dr. Ahmad Al-Moujahed, Assistant Professor of Ophthalmology at Stanford University School of Medicine, Dr. Hendrik Scholl, Chief Medical Officer of Belite Bio, and Dr. Samarendra Mohanty, President, Chief Scientific Officer, and Co-Founder of Nanoscope Therapeutics. Welcome. Dr. Moujahed, could you begin by segmenting the IRD treatment landscape by disease stage? Which patients could potentially benefit from disease-modifying therapies, and which patients have lost enough photoreceptors that a restorative approach, such as optogenetics, could become more relevant? Yeah, absolutely. My pleasure. Usually we can divide the disease into early, intermediate, or late-stage diseases where disease-modifying therapies or gene therapy are more appropriate for early and intermediate stage. Once there is a severe loss of the photoreceptors that it's basically difficult to restore or to preserve anything, then visual restoration therapies like optogenetics play a role in that, and that will be basically for more advanced diseases. Got it. What constitutes a clinically meaningful benefit in Stargardt disease? How should investors weigh slower DDAF lesion growth against visual acuity, reading speed, contrast sensitivity, and preservation of the fovea? Yeah, that's a great question. We are always looking for functional benefit. However, for these very slowly progressive diseases where we are doing studies for one or two years, it's very difficult to measure any functional benefit. We accept the fact that preserving the structure will reflect an improvement in the function in the long term. Although in two years we don't see functional benefit, we are hopeful that on longer term follow-up or if the drug is approved, in the real world, we will see functional benefit because we think that there is a structure-function association, and this association will be reflected in the real world, basically. It needs a longer-term follow-up, and preserving the structure will hopefully lead to preserving the reading speed or preserving the best-corrected visual acuity or microperimetry, all these functional endpoints. Of course, we need the data to prove that's our thought from these macular diseases. In advanced RP, is BCVA the right measure of therapeutic benefit? Would mobility, object localization, contrast sensitivity, or navigation under different lighting conditions better capture whether a restorative therapy is working or not? Yes, I totally agree with that. Although, of course, it's always good to show improvement in BCVA. For these very advanced diseases, I think functional benefit where patients are able to navigate in dim light or basically have better mobilization and independence, these are all very valid and reliable endpoints because the goal here is to improve the quality of life of these patients. Got it. How do you determine whether sufficient viable retinal circuitry remains for optogenetics or OCT anatomy or retinal thickness or visual field and residual light perception useful predictors, or is there not yet a reliable clinical selection algorithm for that? I don't think there is a reliable clinical selection criteria that we can definitely say, "This is the one that we should rely on." However, based on the concept of optogenetics, we think if there is good remaining inner retinal tissue on OCT, that will be a good signal or a good selection point that there will be benefit from optogenetics. Of course, having some remaining vision, at least light perception, we probably will see more effect, but I don't think that's proven yet. I think the main thing is having enough inner retinal structure and, of course, having intact optic nerve, which usually is not the case in most of these diseases. Got it. Thank you. Which are affecting photoreceptors. Thank you. Dr. Scholl, I understand that Belite Bio's DRAGON trial demonstrated a 35.7% reduction in annualized macular lesion growth. How should we translate that percentage into something tangible for patients? Is it going to be years of preserved foveal anatomy or delayed legal blindness or preserved reading ability? First of all, it's important to understand that DDAF, definitely decreased autofluorescence, as established by the ProgStar study group in the last decade, has been shown in histology to be associated with complete degeneration of RPE, retinal pigment epithelium, and photoreceptors. If we can save photoreceptors from degeneration, this will eventually turn into a clinical benefit, as was just pointed out earlier, right? The same logic applies to GA, and that was the basis of market authorization by the FDA of the complement inhibitors. You mentioned the rate of 35.7% reduction in lesion growth. I would rate this as substantial. Just to put this into perspective now for geographic atrophy across the pivotal phase III trials, complement inhibition slowed the progression of geographic atrophy by 21% in OAKS, 12% in DERBY, 14% in GATHER2. This, although GA lesion growth is two and a half times faster than in Stargardt disease. Got it. The trial reported minimal visual acuity changes in both arms over 24 months. What evidence gives you confidence that the imaging benefit will eventually translate into a functional benefit? Over what time horizon should that separation become measurable? Yeah. That's a very important question, right? We all would like to help visual function of our patients. However, when you think about why ProgStar was implemented, with the help of the FDA, by the way, at the time, and funded by Foundation Fighting Blindness, it was clear that visual acuity, as such, would decline so slowly that it would not be a good endpoint for any trial in a reasonable amount of time. To provide some flavor, in ProgStar report number 10, we had shown that the average visual acuity decline was 0.55 letters, 0.5 or half an ETDRS letter per year. Even if a therapy would arrest progression completely, which is obviously a very high bar, a 1.1 letter difference benefit would not be observed before the end of two years. At the same time, we know that almost all patients with Stargardt will reach the legal blindness level in their lifetime, most of them early in life. The life expectancy at the disease onset shows variability, but it's typically in the teens, meaning that the life expectancy of Stargardt patients is typically in the order of magnitude of 60 to 80 years, leaving many decades for vision to decrease and reach the legal blindness level. Got it. How dependent was the treatment effect based on the baseline anatomy? I mean, did the efficacy differ according to foveal involvement, baseline lesion size, age, or ABCA4 genotype, or the presence of DDAF at enrollment? Yeah. That's an excellent question. All these variables are important. All patients in the DRAGON trial had DDAF at baseline, by the way, almost identical of what was studied in the ProgStar study. Almost all patients in DRAGON had foveal involvement. We know that a DDAF progression depends on baseline lesion size. Maybe just a footnote here. It is still questionable what kind of corrective measure would allow to get rid of baseline lesion size. This was just discussed at the annual meeting of the American Society of Retina Specialists again, right? You can use growth rate, you can use square root transformed growth rate, or perimeter-adjusted growth rate. None of them allows to get completely rid of baseline lesion size, as we know in geographic atrophy. This was taken into account, obviously, baseline lesion size, because there is this dependency. We used a specific model, namely a mixed model for repeated measures, MMRM, that would allow to take baseline lesion size into account. When you look at the data of the DRAGON trial, taking into account all these variables, the error bar of the lesion size at all measured time points was relatively small, suggesting to me at least that the treatment effect may not have been strongly dependent on baseline factors. A specific comment for genotype. Over decades, I have studied genotype-phenotype correlation, but ABCA4 is specifically challenging because we need to understand that more than 2,800, the number is increasing every month, more than 2,800 pathogenic mutations are known in ABCA4, and patients carry two mutations, right? It's typically a compound heterozygous state. Some patients are homozygous, but most patients are compound heterozygous, meaning that they carry two different mutations. This fact makes any pharmacogenetic effect essentially impossible to be identified. Long story short, in the DRAGON trial, we have not found a specific dependency on ABCA4 genotype, and we feel that this treatment will be a candidate for all patients of all genotypes in ABCA4. Got it. Where is the optimal intervention window? Should tinlarebant be started immediately following a molecular diagnosis, even before a patient experiences substantial functional loss, or only after documented progression of the disease? Yeah. In DRAGON, we started patients, as I pointed out, with an established lesion because the trial needed an approval endpoint. This is something you need to study that is reliable. Also, lesions could not be too large at baseline to capture progression reliably, so it needed to be in the imaging window. Right? This, however, does not mean that tinlarebant would not work at earlier disease stages, meaning smaller lesion or even no lesion, or later disease stages with much larger lesions. We know that Stargardt progresses inevitably. It takes very long, as was discussed, stressed earlier. ABCA4, I think that that is a very important finding, belongs to the few disease genes amongst the more than 300 known to cause retinal disease, where patients can develop no light perception, NLP. One of the few genes where you can actually experience NLP. Therefore, in my opinion, patients at the U.S. legal blindness level may still benefit from the treatment because further visual acuity and visual field loss can be slowed down and complete blindness be delayed or prevented. Of course, patients with no foveal lesion and perfect vision could benefit the most as they have more photoreceptors remain that can be preserved. My point is a timely treatment would be recommended. Thank you. Dr. Mohanty, could you explain precisely what kind of vision MCO-010 is expected to restore? Are patients gaining standard image-forming vision, improved light localization, better contrast sensitivity perception, or a new visual signal that could require cortical adaptation and rehabilitation? Thank you. Yeah, sorry. Ahmad, go ahead. No, sorry. Go ahead. I was asking Dr. Mohanty. Samarendra. Samar, I was asking. I'm sorry. Yeah. This is a nice segue to what Hendrik was saying and Ahmad also alluded. The vision in this RP disease is very complex in the sense it's not just defined by visual acuity, but visual field, and that will define their activity of daily living. Those visual field is very much involved in your mobility and how you're seeing when you are in a mobile environment. While visual acuity will tell you whether you are able to read, and this will all depend on also stage of the disease that this patient is there. To put them all into one perspective, however, what Hendrik was saying, if you consider zero logMAR, which is 20 by 20 vision, and patient can become NLP, which is logMAR 4. There are four logMAR decline that happens over 100-year period. Every 25 year, there's a one logMAR defined. It's not exactly linear. We have characterized 75,000 RP patients and we have seen whether in early stage it may be 0.4 logMAR, which is two letters per year in RP patients, then i t goes down to 1.5 letters or 1.2 letters. A publication is about to come back from this whole big database of research that we have done, natural history of these patients. That being said, MOGENRY or MCO-010 is targeted to inner retinal cells which remain intact. As we have seen in our clinical trials, whether it's a 18-year-old to 84 years old, have improved by this intervention. We have seen from electrical stimulation, Argus, when higher order visual circuitry remain preserved in these patients, the optic nerve and in LGN on visual cortex. Of course, there is a learning. This is not completely new signal because bipolar cells are close to photoreceptors. Of course, bipolar cells are not intended to give true color vision like you'll see in three different cone cells, but it's well close to the photoreceptor that lot of visual processing circuitry is preserved. Theoretically, by targeting bipolar cells, they are 6 micron in cross-section as compared to 2 micron. Instead of 20 by 20, theoretically, you will get a 20 by 50, 20 by 60 vision with bipolar cell transduction. We have seen this in some patients in our trials who went from all the way light perception, which is close to logMAR 4 to logMAR 0.4, which is 20 by 50 vision. That's a theoretical possibility of enhancement in BCVA. Coming back to which endpoint the patients, not only half of almost patients improved in BCVA, but also other patients improved. Those who could not be measured in the BCVA tool improved in mobility and shape discrimination. That is owing to the dynamic range of the tools that we are using. It's not that visual acuity cannot be improved from NLP to LP to hand motion. We were only measuring with a scale using a single scale, which is Freiburg visual acuity. That's why our floor was logMAR 2.2 and above. Definitely by measuring hand motion, counting figure, or LP/NLP, visual acuity. In those sense, those are very meaningful for these patients, and we see 100% all patients improve in one of these key efficacy assessment. If I understand correctly, those visual acuity improvement can be translated into real-world activities, right? The patients can, after therapy, they can do in terms of recognizing faces, identifying objects, or navigating a room, or reading larger print, or function independently in the environment. You're absolutely right. Most of the patients improved by actually 0.6 logMAR or more, which is six lines of vision. That actually translate to 20 years of vision, what they were seeing. Patients are reporting anecdotally, but also if you see the natural history, a 0.6 logMAR means you are giving them vision 20 year back. This is not about slowing down or arresting the vision, but really restoring and giving them back 20 years of vision. You are absolutely right, the things you mentioned, looking at their near and dear ones, doing activity of daily living, identifying cooking, doing cooking, finding the fork on the table, or picking up object from refrigerator. These are most devastated patients. They're able to do all this work anecdotally, and we have captured a lot of them in patient-reported outcomes, and those are correlating with the BCVA and mobility and shape discrimination tests. What baseline characteristics predict response? Do patient need a minimum number of surviving bipolar cells, a particular retinal thickness, or preserved optic nerve function, or evidence that the visual cortex remains responsive for the patient to respond? Yeah. As I mentioned, all patients that are dosed have responded in one of the key efficacy outcome. We do not see in any of the patient there was optic nerve dysfunction. Of course, that is a necessity. If your optic nerve is degenerated, signal cannot transfer. None of the patients were also excluded during screening period due to the retinal thickness. We enrolled patients whose retinas are as thin as 60 micron, as thick as few hundred micron. We have found with the limited data set that we have, we found that if the retina is more thicker, they can respond much better because they have more number of bipolar cell. As you know, bipolar cell layer is multilayer cell. Most of the patients have at least single layer, but if you have more layers of bipolar cells, I think they are showing to be more effective probabilistically in BCVA. Those patients who did not improve in BCVA, as I mentioned, they improved by light sensitivity test in mobility or self-discrimination. Are you saying basically there's no complete non-responders? Every patient just respond more or less? Yes. All 100% patients improved in one of these three key efficacy endpoints, as Ahmad was mentioning that is important, equally important, not just BCVA, but whether they can perform mobility test, self-discrimination test, which we have validated through an independent observational study. All patients improved in one of these three key assessments. This is durable. Got it. Thank you. Dr. Moujahed, could you provide us with some initial impressions with these two investigational therapies? Yeah, absolutely. I think both are really promising and have a potential of improving patient outcomes. We don't have any treatment for both of these conditions, including Stargardt or advanced RP. I think they both have a potential of either for Stargardt, slowing down the progression of the disease or for RPs, advanced RP for Optogenetics, is to restore some vision. I think they are both very promising with different profiles of efficacy or even maybe signal of side effects. In your view, are these patients easy to identify, or they could be lost during the diagnosis and referral process? Overall, I think especially nowadays patients who are early in the disease process on the anatomy preserving treatment. However, I will still offer it to patients with advanced disease, and I think they will still probably benefit. The major benefit will be for patients who still have functioning photoreceptors. Thank you. Dr. Scholl, in the clinical trial, there has been some reported side effects or adverse events, which include delayed dark adaptation, xanthopsia, and night vision impairment, which could affect chronic adherence in younger patients. Can you tell us about the duration and severity of these events, and how do they resolve with continued treatment, or a dose interruption, or could they potentially lead to a treatment discontinuation? Overall, there was a total of only six SAEs reported in the study. Four of them are, to be clear, in the placebo group. All events were non-ocular, and four assessed as unrelated, two assessed as unlikely related to the study treatment. The overall safety profile was very manageable when it comes to systemic safety. The ocular events in the DRAGON trial are consistent with the anticipated pharmacologic effect of tinlarebant. Again, the majority of the events were mild. Most resolved while on study. Delayed dark adaptation is a very specific symptom and also very specific side effect of tinlarebant. Delayed dark adaptation is part of the disease symptoms of Stargardt itself. When you give tinlarebant, you would not make delayed dark adaptation better. It was an important finding that any complaint, if there was any, we talk about a third of patients, that was only temporarily reported and resolved for most while being on the study. Interestingly, at the end of the DRAGON trial, at month 25, what we call end of treatment visit, both treatment groups, both the tinlarebant and the placebo group, showed only very small changes from baseline when measured dark adaptation time, because that was explicitly measured. It appears that two years into the trial, being chronically on 5 mg per day tinlarebant, there was not a significant measurable effect on dark adaptation time delay. The other is xanthopsia, which is a very interesting word by the way. It means that the visual scene is discolored, in this specific instant, yellowish. If it's bluish, it's called cyanopsia. If it's red, it's called protanopia. Right? Overall, we can combine them and call them chromatopsia. This is not color vision deficiency that is chronic. That is something that is related to light adaptation. We just discussed dark adaptation. Now we go to light adaptation. There's also a light adaptation process in the human eye, namely when you go from dark to light. This doesn't last for minutes. Dark adaptation time would be 20+ minutes for full dark adaptation. For light adaptation, this is very brief, seconds to minutes. During that time, a patient can experience a discoloration of the visual scene, for example, yellowish. We will call it xanthopsia, meaning the patient would see everything, would recognize faces, would be able to read, but everything appears yellowish for seconds or minutes. In the future, when tinlarebant will be on the market, patient education will be key. With every medicine, there's a risk-benefit discussion. For patients, what counts really is preservation of cones in any retinal disease. Patients will need to understand the side effects of tinlarebant relative to the preservation of cones and what tinlarebant actually does to allow to slow progression of their disease and keep them on better vision for longer. Got it. For patients receiving tinlarebant, what kind of monitoring would be required in routine practice? Would patients need periodic serum RBP4 testing or vitamin A monitoring? Liver testing? What could trigger a dosing interruption or permanent discontinuation? Currently, I'm still seeing patients one day a week, and currently without any treatment. I offer my patients yearly monitoring visits, which would include fundus autofluorescence imaging and OCT imaging, which is fast and is standard of care. Some patients actually would like to be seen six-monthly. Other patients would only be seen every two years or so. In the future, with tinlarebant available for therapy, I would believe that six-monthly visit with retinal imaging will be a reasonable monitoring scheme. RBP4 testing and/or vitamin A monitoring in high frequencies likely are necessary in my opinion. We did not see that tinlarebant had an effect on liver health in the DRAGON trial, none. Therefore, monitoring liver enzymes is likely unnecessary. Measuring dark adaptation is a lengthy procedure, typically only being done in academic centers and will unlikely be offered. Personally, I believe that simple history taking to monitor possible symptoms will be sufficient. We did not see much dropout during the DRAGON trial, accordingly, I do not anticipate patients needing to discontinue treatment with tinlarebant. Got it. Thank you. Dr. Mohanty, I understand the company has reported about three years of improvements with the treatment of MCO-010. Can you tell us exactly how durable the benefit could be biologically, and whether there are mechanisms that could cause efficacy to decline, such as loss of transduced bipolar cells or continued retinal remodeling? No, that's an excellent question. I think we'll be only gene therapy who in the U.S. will be launching with the data. By the time we launch, we'll have five-year data. Currently, we have four-year durable data, and that we'll make public soon in the fall meetings. That being said, from a mechanism of action perspective, unlike other gene therapy where you will have difficulty in, for example, in dividing cells. In systemic gene therapy, I'm saying, where cells are dividing, there is a loss of that protein. Here, the protein is in the post-mitotic mature cells, and AAV forms an episome, which is supposed to last over a durable period. The animal studies, for example, that has been done, if you translate to humans, it will be decades of expression that will last. None of the mutations that is causing RP are directed towards bipolar cells. They're directed towards RPE or photoreceptors, the outer retina. Because of those and the evidence that we have seen from the patient across 18 years to 84 years, we don't see a lack of efficacy in patients because when they're exposed to more than 60 years. From an expression point of view, this is, again, to repeat, this is an episomal expression, and the protein is not being secreted. This protein is actually bound to the membrane. It's like a solar cell on your home. Molecular solar cell. It's not continuous, it has to be produced and released to the vascular system or elsewhere to function or improve some outcome. We believe this will provide a very long-term durable expression. We have data from, as I mentioned now, almost four years from these 35 patients we have dosed across trials, that is like 100+ years of durability we are seeing across these patients and safety. We believe that this will be a durable treatment over decades of lifespan of these patients. Real-world evidence is going to provide that concrete confirmation. Yeah. I noticed that Nanoscope has discussed bilateral functional observations following unilateral administration. What is the proposed biological mechanism, and how are you distinguishing a vector transfer from testing variability or cortical adaptation? What are the safety and regulatory implications if vector can reach the fellow eye? It's an excellent question. We are not the first one to discover this. As you know, other LHON programs, any intravitreally delivered gene therapy, there are publications. We have seen it from early 10 year back from our preclinical studies that the vector transport through optic chiasm to the other eye. The two eyes are a connected system. Because of that particular reason, we never use the fellow eye as a control in our randomized controlled trial, and that's what regulators aligned with us, and we have a separate same control arm. That being said, this is a benefit in disguise because these IRD patients, the IRD is caused by a genetic mutation caused by lateral deficiency. This outer retinal degenerative disease happen bilaterally. With a single unilateral administration vector going to the other side and improving is a positive impact. In case of bilateral administration, there can be synergistic effect that has to be seen. We have not proven it in our clinical trials. We believe the drug will outperform in real-world when there is a bilateral injection given. Safety point of view, we have done studies in animals with bilateral dosing. There is no safety findings. In our clinical program, as I mentioned across three trials, there are 100+ years of exposure to the drug, and we have no single SAE in either injected eye or in the other eye or systemically, which is related to MCO-010. Those all give us good confidence that this drug will be safe and effective and durable, as shown in our randomized and follow-up trials. How should investors think about the addressable population? Would an initial label likely be restricted to legally blind or severely impaired RP patients? Yeah. Initially, we are targeting the complementary market, what Belite Bio is, for example, up to legally blind or so. We are primarily towards legally blind and worse patient because that's where the photoreceptor losses happen and primary mechanism of action is in play. We have published many papers, both in RP and in Stargardt disease, where we are actually targeting bipolar cells. We are seeing improvement in anatomical stabilization of the retina, not in terms of lesion growth, but in terms of the thickness of retina is getting stabilized due to the mechanism because now bipolar cells are functional, and earlier they were more degenerating when there were no signal coming to them. Now because they're functional, they're preserving the retina better. We have shown it in mice models of RP/Stargardt, and we have also data in NHP model of retinal degeneration. We are not the only one. There are other publications which are recently coming out in animal models that's showing. That being said, in real world, we will be expanding towards better seeing patients, better than legally blind patients. That will initially our target population is legally blind patients. Thank you. Dr. Scholl, for Stargardt disease, how large is the realistically identifiable and treatable U.S. population at launch? Of the estimated prevalence pool, how many patients have a confirmed biallelic ABCA4 diagnosis? We know that inherited retinal diseases remain underdiagnosed, which is why disease education and patient identification remain important areas of focus. The estimated prevalence of Stargardt disease in the U.S. is roughly 50,000 to 55,000 patients. We are continuing to our extensive market research to understand the patient community, their diagnostic and treatment journey, and the broader care ecosystem to inform our efforts as we move toward potential commercialization. Got it. Thank you. Dr. Moujahed, if both therapies on the market in 2027, would you readily adopt these therapies, and what could be your residual concerns after adoption? Yeah, that's a good question. I would definitely start, these patients are always desperate for new treatments, I will definitely discuss this with my patients. I would recommend starting the treatment for both of patient populations with discussing the benefit that is reported in studies, warning them about the side effects at least, and monitoring them probably closely for the first time. If we are starting a new pill, for example, instead of maybe seeing them in six months for the first time, I will see them maybe in three months just to check on them on the side effects, more than to check on any change in their retina, and then start extending. If I'm treating a patient with a gene therapy, I will definitely maybe choose the worse seeing eye and monitor the patients for a few weeks before starting treating the next patient, just to start slowly. I would definitely start both patient populations on these treatments or at least offer it to them. Thank you. Yi, if I may interject here, I just want to say maybe Ahmad won't have the opportunity in the U.S. to dose both the patients because our initial indication for U.S. is RP. Though we are planning for a broader indication level in ex-U.S. market, in Japan and Middle East and other places. In U.S., it will be primarily the RP, where I think Belite Bio is in Stargardt, Ahmad won't have that opportunity or decision-making to make next year. We hope the U.S. regulator will follow suit or with real world data or our new trial, we will expand into Stargardt in U.S. in near future. I just wanted to make that clarification so that your audience knows that we are focusing RP in U.S. next year. Thank you. Dr. Scholl, obviously, we know that you have completed the NDA submission recently. What are the remaining regulatory variables following the NDA submission, and what should investors monitor regarding filing acceptance, potential advisory committee review, or label breadth or post-marketing commitments? We are awaiting our Day 74 letter from the FDA, which as you know would convey acceptance of our application. It will provide us with a PDUFA date and set the tone for the remainder of our review. That milestone would be the next one to watch for. Since we were given Breakthrough designation, we believe that we may get Priority Review from the FDA. Got it. How do you position tinlarebant relative to competing visual cycle modulators? Is the competitive advantage primarily efficacy, once-daily oral administration or intervening earlier in the disease? I would like to correct, if I may, that tinlarebant is not really a visual cycle modulator. The visual cycle is left uninterrupted with tinlarebant. It is the substrate for the visual cycle which is reduced. Eventually it has an impact on what happens in the visual cycle because you have less substrate, but the visual cycle as such is left in its physiological state, right? Personally, I believe that disrupting the visual cycle is likely unhealthy, right? We know of genes that cause visual cycle disturbance that are known retinal disease genes. Vision restoration, which was discussed using various approaches, visual prosthesis, stem cell therapy, which are other approaches, but also optogenetics as we discussed. These are completely different approaches. Patients undergoing treatment with tinlarebant could still benefit in the future if vision restoration approaches really work and become available. In other words, such treatments would potentially be complementary. The observed efficacy, the ease and safety of once daily oral administration as we have with tinlarebant, and the opportunity to intervene early are all competitive advantages of tinlarebant. Thank you. My next question is for all the panelists. The question is, what will be the bigger commercial bottleneck? Is it finding a genetically confirmed patient, convincing physician that the endpoints are meaningful, securing reimbursement, building treatment center capacity, or managing patient expectations? Dr. Scholl, you can start. I'm happy to. Thank you. We are thinking about all these considerations. Focusing on commercial readiness on our genetic testing education efforts, discussions with payers around reimbursement and patient education. We have a highly experienced team in place to successfully launch this treatment, which, if approved, will be the first approved treatment in this space. Dr. Mohanty? I think similar to Hendrik, we are also approaching the pre-commercialization activity so that we have a successful launch. To answer your question about genetic diagnosis, as we saw in the ICER public council as well as we are talking to regulators, there are more acceptance of not requiring a genetic testing because 40% of RP patients, the genetic mutations are not yet associated to be with RP, are not yet confirmed to be pathogenic. Because of that, we want to have regulator not put such a condition on genetic testing. Payers have also larger acceptance towards that. Regarding the treatment center, because here we are doing an intravitreal administration and which is a most widely known for medical practice today. We will not be requiring specific training or training centers, unlike other gene therapy which are subretinal or of that nature. Definitely we are onboarding commercial expert team who have substantial experience in market access, in marketing and sales of rare and genetic therapies, and we will be well-positioned early next year to launch this product. Thank you. Dr. Moujahed, could you comment on this? Absolutely. I think from like a physician standpoint, I think for a new treatment that potentially could be expensive, I think securing reimbursement or negotiating with payers and making these processes as easy as possible for prescribing physician is probably one of the major issues that we are looking forward to make it easier for us, basically. I think I have enough patient population and expertise in delivering the treatment. It's just we want to make sure it's covered. Yeah, that's definitely. That has been our focus, especially for this gene therapy. We are making sure that multiple options are given, whether specialty distribution or specialty pharmacy with white glove service and also proper compensation and of the effort. I think we are working towards that, and we will have some partners as already partnership announced publicly and will have more to come in near future. We'll make sure the patient journey and the provider journey is very smooth and the payers are understanding the value of these long-lasting gene therapies that we are developing and will be amenable to provide payment to the sponsor. Thank you. My next question is for Dr. Scholl and Dr. Mohanty. What are the development regulatory and/or commercial milestones investors should use to evaluate the investment opportunity presented by your company over the next 12 to 18 months? Dr. Scholl? Sure. Thank you. As I mentioned previously, FDA acceptance of our application is the next major milestone for Belite Bio, and then the PDUFA date communicated in our Day 74 letter gives us a target for when we would anticipate the FDA review to be completed and enable Belite to make tinlarebant available to all U.S. Stargardt disease patients. Dr. Mohanty? For Nanoscope, similarly the acceptance of the BLA and the 74-day letter and PDUFA date will be very important milestone that you should look for in next couple of months. Beyond that, we will be starting randomized controlled trial both in Stargardt and GA. Enrolling those patients, completing enrollment will be another significant milestone. Beyond U.S., geographically, Japan, as I mentioned, PMDA through Sakigake consultation is completing their review of our application. Inspections are planned very soon, in this quarter. We are expecting also approval from other geographies so that we can launch this drug and make it available globally. There are a lot of milestones, I think, that investors should look for, not just to the U.S. milestone. We are very confident of this broad, again, indication will be another milestone for the community, just having one gene therapy for not only mutation-agnostic, but for many diseases. Actually, 10 different diseases which are being considered by regulators for the same therapy. With one approval, if we can address all those patients, will be a very major milestone for not only Nanoscope but whole community, I believe. Got it. Dr. Scholl, I understand that you also have, Belite Bio also have a GA program. Could you tell us what is the next update for the GA program? Then also in Japan, what is the estimated timeline for the approval for Stargardt disease in Japan? Yeah. Maybe I start with Japan because then we stay in the Stargardt arena. We have been given a Sakigake designation from Japanese Ministry of Health with the goal, the explicit goal, to make tinlarebant the first treatment in the world available for patients in Japan. Japan was not fast enough to participate in the DRAGON1 trial. That led to the birth of the DRAGON2 trial, which is fully enrolled with 73 patients at beginning of the year. It's essentially the same trial design in DRAGON2 as we have for DRAGON1. Our submission to the PMDA in Japan will be based on the DRAGON1 trial results with data out of DRAGON2 on the 15 Japanese patients that are currently being treated in the DRAGON2 trial. The FDA approval is likely to be the first event at the beginning of next year. The approval by the PMDA in the Sakigake designation, so to speak, would follow relatively soon thereafter. When we get to geographic atrophy, as you mentioned, tinlarebant with the exact same dose is being evaluated for the treatment of geographic atrophy as well. Very similar clinical trial design as we had at DRAGON. We look at lesions and lesion growth. The lesions, as you know, in geographic atrophy are called geographic atrophy. It's not as sophisticated as the terminology we developed in ProgStar study that we call these lesions definitely decreased autofluorescent lesions. This is the endpoint we use in the PHOENIX trial. That's the name of this trial as well. 530 patients are in the trial. We are about to have the 12-month data available on all patients. The company has not decided yet if it will perform an interim analysis. If we do that, we would likely do that as we did in DRAGON for a sample size re-estimation. The trial will be completed beginning of the third quarter of next year. Thank you. Dr. Moujahed, could you tell us how do you envision the therapeutic space for IRD to evolve between now and 2030 with the investigational therapies discussed on this panel and any other novel therapies you're aware of that are currently being developed? It's definitely an exciting time for patients with IRDs who will be starting to have different options for these patients. Some of them are easier to administer than subretinal gene therapy. We have advances in all of these spaces, including disease-modifying treatments with gene therapy or even without gene therapy, the ones that we're discussing today. We have more advancement now in vision restoration, whether it's optogenetics or other approaches. I think it's a really promising time for patients with IRDs, and I think we will have, in a few years from now, at least a few more approved treatments for these patients. Got it. Thank you. Dr. Scholl and Dr. Mohanty, do you have any closing remarks for our audience? No, I want to just repeat what Ahmad was saying, that this is exciting time, we want to impact these patients. All of us, the healthcare provider, us, and other company sponsor, we need to look forward to be bringing more and therapies for these patients and whether they will be used in conjunction with each other. The win for one will be win for all of us. I think we are looking this retina space more approvals, and we look forward to working together. In that regard, we have developed novel tools to assess functional vision without mobility, like the shape discrimination tool. We are making it available to other IRD companies now. They are being used in China, in Europe, U.K., and U.S., not just by us, but others. We are very happy that we are working with the community to make not only treatment available, but assessment tool available to really readily assess the outcome so that payers can value the drug in the real world. Thank you. Yeah. Maybe I can then I close by saying I have seen these patients for two decades myself, there has been absolutely no treatment. Now with the DRAGON results showing, I have to say, obviously I'm biased, but an absolutely stunning 36% treatment effect in slowing down lesion growth. This is something that makes the patients that I currently see in Switzerland really happy to anticipate that there will be a treatment soon, and this will be a game changer for the field. This is an exciting time for IRDs in general. Thank you. We are getting to the end of the panel. I would like to thank all the panelists for an informative conversation and our audience for participation. This concludes the panel discussion. Thanks again. Thank you, Yi. Thank you, everyone. Thank you very much