Belite Bio, Inc American Depositary Shares H.C. Wainwright 28th Annual Global Investment Conference

We submitted a very comprehensive package to the FDA being confirmatory evidence. There is guidance of the FDA what confirmatory evidence actually means. Most importantly, it is natural history evidence. We have access to the largest natural history data set that is available worldwide, the so-called ProgStar study, that I had the honor to lead myself a couple of years ago, which has comprehensive data on natural history progression of patients with Stargardt disease that are, and that is also very important, very similar in disease stage compared to the patients we enrolled in the DRAGON trial. We can and did complement our placebo group with a very large cohort out of ProgStar, and this helped to create substantial confirmation of what we found in the DRAGON trial.

Beyond the guidance of the FDA, and that is specific for an oral treatment or a systemic treatment, is that we have data from the fellow eye.

As you know, in paired organ clinical trials, regulators would like to see one study organ, namely the study eye. If you have eye-specific treatments, such as injectables or surgery, what have you, that is where you study your treatment effect. But we have the opportunity, and we did in DRAGON, to study the fellow eye also. Which was very nice and obviously confirmatory is that we found almost the same effect size in the fellow eye, namely 33%. Even the fellow eye data reached a statistical significance threshold.

The answer is a simple yes. Because in the retina space, we have seen a transition starting 2 and a half decades ago with the emergence of high-resolution imaging in clinical care that nowadays in retina clinic, you still look at your patients obviously, but you look at images. You look at retinal photography, you look at autofluorescence, you look at OCT images. You make conclusions on efficacy of your therapy, on safety, on any intervention, pretty much based almost exclusively nowadays on retinal imaging. Healthcare providers in the retina space are very much used to look at high-resolution images, and they understand, FDA understands, that if you preserve photoreceptors, that is a good thing. If you lose photoreceptors, it is a bad thing. The immediate relationship between imaging and we call it structure, and visual acuity, we call that visual function.

There are other visual function measures such as visual field measures, specifically from microperimetry, can be complex. Visual acuity, as an example, depends mainly on the fovea and nothing else. Visual field depends on all photoreceptors that are being imaged. But clinicians have a very good understanding what it would mean for a given patient if you have loss of photoreceptors in a given area and how much loss of photoreceptors there is.

Yeah, so this is an excellent question. You could say bad luck for Belite Bio that in the trial, the placebo group progressed somewhat slower than what was found in the natural history study in ProgStar. Still, we had a very strong treatment effect and still a very low P value. I think that rather validates the finding in the DRAGON trial. When it comes to an explanation, this is maybe counterintuitive, but it is confirmed by what was found in ProgStar. We can be very specific. I can refer the interested audience to table number 2 in ProgStar report number 17.

This is the 24 months data out of ProgStar. What was found is that the DDAF progression rate, meaning how fast lesions of almost complete atrophy of the outer retina progressed in the natural history study, was not different amongst subjects younger than 18, between 18 and 50, and if at all, slightly higher or slightly faster in subjects that were older than 50. Meaning that DDAF progression rate is relatively homogeneously distributed amongst all the ages. That is important when it comes to generalizability. This is also your question, right? The generalizability of the data to the total population out there. Given the ProgStar data and the relatively homogeneous progression rate amongst all age groups, we feel that the findings of DRAGON can be generalized to all patients affected by Stargardt disease.

It is an excellent question. We did comprehensive sensitivity analysis. As an example, we looked at the treatment effect size in the different races in DRAGON trial. Populations of East Asian descent, European descent, African descent. We looked into the different geographies where we conducted the trial, U.S., U.K., Europe, China, Taiwan, and Australia. We looked into sex effects, males versus females. We looked into age effects, younger patients between 12 and 20 years old that we treated in the trial up to 20 years. Long story short, we did not find any specific effect, meaning stronger or less strong treatment effect in any of those analysis. Which is, I feel, positive because that allows, again, to answer the question before about generalizability of the DRAGON trial results.

Given that we found no specific treatment effect, for example, in younger patients or older patients, allows to generalize to essentially all patients affected by Stargardt disease regardless of race, geography, sex, or age.