Belite Bio, Inc American Depositary Shares Morgan Stanley 24th Annual Global Healthcare Conference

Sure. Belite started as a spin-off of the parent company, Lin BioScience, which is also listed in Taiwan. We currently have our leading pipeline called tinlarebant in both Stargardt disease and geographic atrophy. In Stargardt, we have completed our phase III study and submitted for the FDA, which they already accept the NDA with the priority review, with the PDUFA date for next February 12th. We are also running in parallel a second phase III Stargardt trial called DRAGON II. That is mainly for the reservation for Japan. For GA, we have a fully enrolled global phase III study called PHOENIX is ongoing.

Yeah, happy to. Stargardt disease was described by Karl Stargardt about a century ago. It is amongst all the genes that, if mutated, would lead to retinal disease by far the most prevalent. The disease has, in populations of European descent, a prevalence of about 1 in 6,500. The prevalence is somewhat lower in East Asia and actually higher in populations of African descent. The estimate given the penetrance and mutation rate in the gene that 47,000 to 59,000 patients in the U.S. are affected by the disease. We currently, that is the conclusion from our research data, that 20,000 patients are currently clinically diagnosed. Amongst those 20,000 clinically diagnosed patients, more than half carry a genetic confirmation, meaning that at least one mutation was detected in the ABCA4 gene.

Yeah. Stargardt disease is a very important cause of legal blindness. Amongst all the inherited diseases, it is by far the leading cause of blindness in adolescents and young adults. The disease typically starts in childhood and early adulthood and invariably gets worse and worse, leads to legal blindness in almost all cases. That is rare, but it can happen, can lead to no light perception. There's no light detection, that no light detection remains, meaning the disease kicks in early on in life and is severe, meaning that there's almost no patient that would not have any diagnosis. Because if you have such a severe disease and you cannot be corrected with glasses and your vision is down to 20/200 or a similar level, it would be an unlikely scenario that there was never any diagnosis made. The question is how precise is the diagnosis?

Because clearly, in order to initiate treatment, we need a precise diagnosis of Stargardt disease. It's not so difficult, I have to say. I speak as a clinician, and I still see patients one day a week in Switzerland. The disease can readily be diagnosed, especially nowadays with imaging that we have in the clinic, which is fast and reliable and very precise. To make the diagnosis is not so difficult. But we anticipate that when tinlarebant is on the market, that the vast majority of patients would need to be or will be followed by a retinal specialist, meaning they need to be referred to a retinal specialist in the future. Many patients are currently being seen by retinal specialists. Amongst all of those patients, again, the majority will be seen by so-called IRD, inherited retinal disease specialists.

We have a very good understanding in the U.S. where are the centers of excellence and where are those IRD specialists located.

Yeah. Karl Stargardt in 1909 described a macular degeneration. By the way, it's very similar to age-related macular degeneration. It's just the patients are 60 to 80 years younger, where the macular shows atrophy, and around the atrophy, it is surrounded by flecks. He called it flecks at the time, yellowish flecks. We know exactly what these flecks are made of, namely toxic bisretinoids that accumulate in the retina in Stargardt disease. When we use so-called autofluorescence imaging, which is a standard tool in retina clinics nowadays, where you shine in blue light and we detect the outcoming light from the retina, we see that these flecks light up, and those flecks indicate the cause of the disease.

The cause of the disease is this constant accumulation of toxic bisretinoids, which cannot be detoxified, because the protein that would be important to do so is dysfunctional because of the mutated underlying gene with the name ABCA4. Those ABCA4 mutations, therefore lead to dysfunction of ABCA4 and accumulation of toxic bisretinoids. The consequence of the disease of these toxic bisretinoids is then macular degeneration, and this again can be very precisely imaged with fundus autofluorescence imaging. Tinlarebant allows to address A2E and bisretinoid accumulation in photoreceptors and the underlying tissue called the retinal pigment epithelium by targeting the so-called RBP receptor that is unique in the eye. The eye has a unique requirement to access vitamin A due to this receptor, no other organ.

Tinlarebant allows systemically to lower retinol bound to retinol-binding protein 4, therefore, less compound is available for the receptor called the RBP receptor, or specifically STRA6. Because of lowering influx of vitamin A into photoreceptors and no other organ in the human body, the underlying material, if you will, the substrate of forming the visual pigment in the photoreceptors, this process is called the visual cycle, is reduced, and that allows to reduce A2E accumulation and therefore to preserve vision.

The best outcome measures in macular degeneration have been developed over the last two decades, in conjunction with the FDA. The FDA is very aware that the underlying reason to see is photoreceptors that are being preserved. If you lose photoreceptors, you lose vision, and therefore preservation of photoreceptors is clinically valuable and beneficial. Therefore, the FDA, one and a half decades ago accepted preservation of photoreceptors as imaged by autofluorescence imaging as an approval endpoint, and that led to the approval of SYFOVRE and IZERvay for geographic atrophy. In Stargardt disease the situation is essentially identical, because we have a more technical, more precise term, if I may say so. Namely, we call these areas DDAF, definitely decreased autofluorescence, that were shown to progress at a predictable rate in the worldwide natural history study called ProgStar, and can be precisely measured from autofluorescence images.