Good afternoon. Welcome to the H.C. Wainwright BioConnect Investor Conference and NASDAQ. For this session, we will have a Good afternoon. Welcome to the H.C. Wainwright BioConnect Investor Conference and NASDAQ. For this session, we will have a Good afternoon. Welcome to the H.C. Wainwright BioConnect Investor Conference and NASDAQ. For this session, we will have a Good afternoon. Welcome to the H.C. Wainwright BioConnect Investor Conference and NASDAQ. For this session, we will have a fireside chat with Dr. Hendrik Scholl, Chief Medical Officer of Belite Bio. Thank you for joining us. Thank you for having me. Dr. Scholl, you joined Belite Bio last September. Is that right? That's correct. Could you tell us what is unique about Belite Bio that made you join the company? Keep in mind that I have been seeing patients affected by Stargardt disease and AMD for more than two decades in Germany, the United Kingdom. I was Professor at the Wilmer Institute for more than six years. I was the principal investigator for the largest natural history study ever conducted for Stargardt disease, the ProgStar study in the United States, and then continued to see patients as a chairman in Basel. I always wanted to be connected with therapy for these patients because these patients inevitably go blind. I have been collaborating with Belite Bio for more than half a decade in various capacities, and this obviously is a major opportunity to get as close as possible to the first therapy ever for Stargardt disease. I took that opportunity, and I'm very happy with it. Could you tell us, your lead candidate is Tinlarebant. Could you tell us how Tinlarebant's mechanism of action is differentiated from other competitors? Happy to. Maybe first of all, it's an oral compound. It's a chemical compound. It addresses the most important part of the pathophysiology of Stargardt disease and late dry age-related macular degeneration. I think there's a lot of activity in the field of gene therapy. I have been very active in that field as well. Specifically for Stargardt disease, there's a problem, namely that the ABCA4 gene is very large, exceeds the packing capacity of the typical vectors that are being used for gene therapy, namely AAV. There are more than 2,800 variants in the gene. Plus, when you develop gene therapy for a condition that affects the macula, the only way currently to efficiently transfuse photoreceptors is subretinal delivery. Surgically, that means you have to detach the macula in order to have a treatment effect for macular diseases. This is absolutely counterproductive. I speak as a vitreoretinal surgeon, and always when you detach the macula, you deteriorate the situation and you harm photoreceptors. When it comes to the mechanism of action of Tinlarebant, it addresses retinol or vitamin A availability in photoreceptors and the RPE. We need vitamin A in photoreceptors. If ABCA4 is mutated, then we get an accumulation of ultrasensory retinal, which is part of the visual cycle, and that is toxic itself. Plus, it forms with other molecules, so-called bisretinoids, that are very toxic. Tinlarebant efficiently reduces the amount of vitamin A in photoreceptors, but not too much, and efficiently reduces the accumulation of bisretinoids at the level of the retinal pigment epithelium and the photoreceptors. This is with an excellent safety profile. This is unique. The only other compound that may be similar, if you will, is deuterated vitamin A, also called Gildeuretinol, where by modifying vitamin A, you reduce downstream the bisretinoid accumulation in photoreceptors. You really give very high amounts of vitamin A to the human body, to photoreceptors. If you do the math, it equals 70,000 international units of vitamin A. Keep in mind, the drug is intended to be used for the rest of the life of the patient. Giving such high amounts of vitamin A, in my opinion, poses a big risk for patients. Thank you. Are there a good number of Stargardt disease patients available in the U.S. that would present an attractive market opportunity for the company? The answer is a clear yes. In the past, it has been difficult to estimate the prevalence of relatively rare diseases such as Stargardt disease because population-based studies are not sufficient to allow us to really estimate the prevalence of Stargardt disease. Many papers still cite an opinion from a publication of 1988 where a Dutch ophthalmologist was asked how prevalent is Stargardt disease. The answer was, oh, it's more prevalent than retinoblastoma, but less prevalent than retinitis pigmentosa. Therefore, I estimate the prevalence to be one in 8,000 to one in 10,000, which is kind of funny that this is still being cited. There is an opportunity in Stargardt disease. It's an inherited disease due to biallelic mutations in ABCA4. There is no non-penetrance, meaning if you carry two mutations in both alleles, you will be affected. Because of that, you can look into genetic databases of the world populations, and you can calculate the number of affected individuals. If you do that, you find that in populations of European descent, the prevalence is one in 6,500. If you look into the prevalence in East Asians, you find that the prevalence is pretty much exactly one in 11,000 to one in 12,000. It is actually a pretty high prevalence. When you do the math and calculate the number of affected patients in the U.S., the number is, taking into account so-called hypomorphic mutations, then you find the lowest number would be 43,000 and the highest number 59,000 patients in the U.S. Long story short, more than 50,000 on average. I think this is a big market opportunity. Thank you. I understand the Tinlarebant is currently being evaluated in two phase III trials named DRAGON and DRAGON II trials. The first DRAGON trial is now on track to be completed in the fourth quarter of this year, right? Can you tell us your expectations for the data readout? What would be considered positive results? Yeah, thank you very much for the question. This is a very important moment for myself because actually at 11:37 today, we received a letter from the FDA of the designation of breakthrough for Tinlarebant based on the interim data that were submitted to the agency a couple of weeks ago. The interim analysis was pre-planned, and about 75% of the data were available and were presented to the DSMB, an independent data safety monitoring board of the DRAGON trial, with a task to provide feedback on safety and efficacy insofar as the trial would fall into a so-called promising zone, which would allow to add 30 more subjects in order to boost conditional power. If no subjects would be added, that would mean either futility or an efficacy signal beyond the so-called promising zone. Since the DSMB provided an additional recommendation, namely submit the data for further regulatory review, the only conclusion that can be drawn, in my opinion, is that there must have been a significant efficacy signal that prompted the DSMB to make this recommendation. We followed the recommendation of the DSMB and have initiated interactions with various regulatory agencies, the FDA, the Chinese FDA, the PMDA, the MHRA, the EMA. We are currently in discussions with all these agencies, with one example that I just mentioned, namely breakthrough designation that was granted actually this late morning today. Therefore, I have high expectations of the final study data that we would have available by the end of this year. The last patient, last visit is September 30th. I believe with the image analysis by the Central Reading Center, then data cleaning and QC, we should have the data available by the end of the year. Congratulations on getting the breakthrough therapy designation. Does that mean the pathway to approval could be accelerated? I would hope so. We have feedback from the FDA. We had that before that if one trial is sufficient would be a review issue. I would believe it's the same with interim data, given the fact that 75% of the data is already available, was available at the time of the interim analysis. The combination of the efficacy and the safety of Tinlarebant plus the fact that our secondary endpoints could represent so-called surrogate endpoints for the primary endpoint would mean that we should be in a strong position to at least discuss with the agency about accelerated approval. It remains to be seen. Meanwhile, the DRAGON II trial is still advancing as planned, right? Can you talk about the status of the DRAGON II? And is DRAGON II having the exactly same trial design as DRAGON I? DRAGON II is based on an opportunistic approach due to the PMDA in Japan providing the SAKIGAKE D esignation with the requirement that Belite Bio would run a phase Ib clinical trial looking into the pharmacokinetics and pharmacodynamics in Japanese patients, plus enrolling at least 10 Japanese patients into an interventional trial. That prompted the DRAGON II trial. Although EMA, PMDA, and so forth do not require a second trial explicitly, we took that opportunity to launch the trial in Japan and invited centers in the United States and United Kingdom to also participate in the DRAGON II trial. If we ever needed a second trial, we would have one. It is currently running. The target enrollment is 60 patients. Currently, 16 are enrolled. Eight patients in Japan have been enrolled, which means we need another two, and we anticipate that to be completed by summer or so at least. The trial design is almost identical to the DRAGON I trial. There are two differences. One, it's a one-to-one randomization between Tinlarebant and placebo, while in DRAGON I, we have a two-to-one randomization. The second difference is that we somewhat lowered the lower threshold of visual acuity from 2,200 - 2,400 to allow more patients to be enrolled into the DRAGON II trial. Otherwise, same intervention, 5 mg per day daily, same primary outcome measures, same secondary outcome measures. In other words, it's almost identical. Okay. Does that mean later this year, you will have data from the 10 Japanese patients from DRAGON II and combined with data from DRAGON, you will be able to submit to PMDA in Japan for potential approval? That is correct. The PMDA is, I mean, I think the SAKIGAKE D esignation speaks for itself. It's keen on having Tinlarebant being market authorized in Japan. It remains to be seen if Japan indeed would be the first country in the world. If you ask me, I would still bet that it will be the United States. Clearly, Japan is very welcoming towards an approval for Tinlarebant in Japan. I guess it remains to be seen whether Belite Bio will launch the drug in the U.S. first or in ex-U.S. territories, right, given the current most favored nation pricing policy. Yeah, this is an excellent, excellent question. I think it was a very good plenary session this morning from 8:00 - 9:00, where this was also discussed. I like the conclusion that we cannot really conclude anything right now, how to position ourselves. I can speak as a physician. I've seen these patients for more than two decades. My big motivation is to get the drug to the patients as soon as possible. I think this is the path we are currently following. You're absolutely right. We will observe closely about future uncertainties being imposed onto the market, the world by the Trump administration. We'll try to find the best path forward. Got it. Tinlarebant is also being evaluated in a phase III PHOENIX trial for geographic atrophy. Do you expect the drug to work equally well in GA as in Stargardt disease? We don't know yet. In Stargardt, the situation is clear, if you will. There's this gene, ABCA4, that is very well characterized. We know exactly what it does. Geographic atrophy is a different beast. It's a so-called complex disease. There are various pathways that contribute to GA. We know that the photoreceptors and RPE are sick, very similar to Stargardt disease. When ABCA4 gene was discovered, it was claimed at the time that this is an AMD gene. I believe that the two diseases are different, but they are so similar. Plus, it has been established that bisretinoids play a role in late dry AMD that I feel that Tinlarebant must be efficacious in geographic atrophy. Since there are other pathways in late dry AMD that may also contribute, you could argue that Tinlarebant may be less efficacious in geographic atrophy. There is one fact that would speak for the same efficacy, namely the pace of geographic atrophy that is typically 2x-3x faster or larger in geographic atrophy, which means that intervention targeting successfully one of the important pathways because of the relatively fast pace could have a similar treatment effect as observed in Stargardt disease. Are there any close competitors in the GA space that you think investors should be aware of, particularly those drugs that are non-invasive like Tinlarebant? Yeah, that's a good addition that you mentioned. We know, I mean, I'm practicing in Switzerland, in Europe. There is no drug available at all. In the U.S., the situation is different. We have two injectables that target the complement system. I'm proud to say that my group in 2008 was the first to show that there is systemic complement activation in AMD. Those drugs make sense. When you look at the treatment effect, at least in the published literature, in the GATHER2 trial, the efficacy signal was 14% reduction after 12 months. When we look at Syfovre, there were two trials. One actually did not meet its primary endpoint with an efficacy signal of 12% in 12 months. The other one, the OAKS trial, met the primary endpoint with an efficacy signal of 21% based on monthly injections, right? I mean, it's a hard sell because the disease will continue to get worse. You think about the treatment effect of about, let's say, 15% of taking those two interventions together, which means 85% of progression remains. This is still on a monthly injection basis for many, many years. This is a hard sell. There is a treatment available in the United States. In my opinion, Tinlarebant would be truly transformative because it's an oral treatment that simply needs to be taken as one pill per day. When we consider other systemic interventions, there is one compound that could be considered similar, namely deuterated vitamin A. This was tested in the so-called SAGA trial that was presented at the last academy meeting last October and was observed to fail its primary endpoint. In our opinion, in our interpretation, there was a trend at least that was shown with deuterated vitamin A. And we feel this kind of supports this intervention, namely targeting bisretinoids in geographic atrophy, right? I would say for AMD patients, that was a not-so-nice piece of information that the trial failed. At least there was a good piece of information that targeting bisretinoids may be or is a good idea. That's exactly what we are doing with Tinlarebant. I think that's the current landscape. Does Belite Bio currently have sufficient capital to complete all the ongoing phase III trials? The answer is a clear yes. Currently, we have $157 million available. That would allow to complete all the clinical trials that are currently running. Okay. That's all my questions. Questions for our audience? Nope? All right. Thank you very much. Thank you very much.