Good morning and welcome to the H.C. Wainwright 27th Annual Global Investment Conference. 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, could you tell us the current development status of Tinlarebant in Stargardt disease, I mean primarily the DRAGON trial, including the estimated timeline to top-line data readout and potential regulatory submission?
Yeah, thank you. The DRAGON trial is a two-year international registration trial on 104 patients with Stargardt disease. The last patient's last visit will be this month. The top-line data readout is expected by the end of Q4 this year, and we aim for an NDA submission in the first half of 2026.
Thank you. Can you tell us the efficacy and safety data that have been observed for Tinlarebant so far in Stargardt disease? How do they compare to potential competing therapies?
Yeah, the DRAGON trial is still masked. The current efficacy data stem from an open-label phase II trial where Tinlarebant prevented the development of atrophic lesions that we call DDAF, definitely decreased autofluorescence, which is an accepted endpoint by regulators, and slowed the growth of these DDAF lesions in those patients who developed these lesions by almost 50% when compared to natural history controls from an age-matched subcohort of the [ProgStar] study that, by the way, I led and implemented when I was a professor at Johns Hopkins. We already know from the interim analysis of the DRAGON trial that Tinlarebant with a dose of 5 mg per day continues to be safe and well tolerated in these adolescent Stargardt patients. At the time of the interim analysis, the overall withdrawal rate due to ocular adverse events was less than 4%.
Now, at the end of the treatment and almost at the end of the trial, the withdrawal rate has remained exactly the same. I think we can conclude that the safety profile is excellent of Tinlarebant.
Assuming positive data from the first DRAGON trial, is there a chance to seek accelerated approval? What type of, what kind of efficacy data would enable the company to seek accelerated approval from the FDA?
Yeah, so following this surprisingly nice and not anticipated recommendation of the DSMB after the review of the interim data to submit the data of the interim analysis to regulatory agencies, we followed that recommendation and contacted various agencies and discussed the path forward for making Tinlarebant available to Stargardt patients as soon as possible. As a result, the FDA granted breakthrough designation based on the IA data. Since the trial will be completed by the end of the quarter, so in a couple of weeks, we will seek full approval in the majority of jurisdictions, including the U.S.
What is the total addressable market in Stargardt disease? Considering the patients enrolled in the DRAGON trial are pediatric patients, do you think Tinlarebant could be beneficial for adult patients with Stargardt disease as well?
Yeah, so indeed, DRAGON enrolled adolescent patients who are most severely affected. Age range was 12 to 20 years in the DRAGON trial. Since Stargardt is an inherited disease caused by dysfunction of the ABCA4 protein, the disease in adults and adolescents is exactly the same. As such, Tinlarebant will work as well in both populations. We anticipate no restriction on age of our label. In other words, the label should include the adult patient population. In a recent meta-analysis of epidemiological and genetic data, we estimate the prevalence of Stargardt to be roughly one in 7,000. If it comes to populations of European descent, the disease is actually significantly more prevalent in populations of African descent and slightly less prevalent in populations of Asian descent. Considering the U.S. population, including Caucasians, East Asians, and African Americans, this would result in roughly 47,000- 59,000 patients in the U.S. alone.
With a market penetration of 40% or so, this would be more than 20,000 patients in the U.S. alone.
Thank you. Last month, a private company called Nanoscope Therapeutics announced the publication of data from a phase II trial of its gene-agnostic therapy in Stargardt disease. The results showed vision improvement at week 48 in adult patients. How do you view these results compared to Tinlarebant data? Is Nanoscope's gene therapy a potential competitor or complementary to Tinlarebant in Stargardt disease?
Yeah, maybe we should not get so much excited about that phase II trial. These were six patients that were treated with this experimental new compound. The company, Nanoscope Therapeutics, developed a technology called optogenetics, which follows the idea to make cells light sensitive that are not light sensitive themselves and are also not made to be light sensitive, not designed to be light sensitive. Some of these cells survive longer than the photoreceptors in Stargardt disease, so they remain. Therefore, they can be targeted. That is also true for other degenerative diseases. I believe that Nanoscope Therapeutics is also working on retinitis pigmentosa. In retinitis pigmentosa, indeed, patients can lose all vision. Also, in the six patients that were treated with that compound in Stargardt, we talk about very low vision.
Patients had vision as low as nine letters as the ETDRS score, which means they would not see any letter at four meters on the chart. We talk about very low vision. There was a very modest improvement, and this was not masked. We have to understand that there's a very narrow illumination window. We can only expect a very modest improvement under very specific light conditions. The cells that are targeted would still continue to degenerate. With Tinlarebant, we aim to prevent vision loss and keep patients on useful vision for much longer, some patients on good or even very good vision. They should never actually get to the stage where they actually would need optogenetics to restore some vision.
It's sort of complementary.
It's complementary in that sense, yes.
What is your regulatory strategy in the U.S., Europe, and other international markets for Tinlarebant?
Yeah, so I mentioned that we will seek full approval with a broad label in the United States. We will do the same in Europe, Japan, the United Kingdom, Switzerland, Australia, and other markets for GA. We will need a second registration trial. The PHOENIX trial that was communicated on July 2nd has just fully enrolled with 530 patients worldwide.
What is the timeline for top-line data readout from the PHOENIX trial in GA?
The PHOENIX trial is about two years behind the DRAGON 1 trial, so we anticipate the top-line data readout in the third quarter of 2027.
2027. Do you believe Tinlarebant's efficacy in GA is positively correlated to its efficacy in Stargardt disease? Why would you think so?
The two diseases are not the same, but both diseases have many signs and symptoms in common. When ABCA4 was discovered, by the way, just around the corner at Columbia University in New York, it was published as a gene that causes Stargardt disease, but also AMD. That was a Science paper in 1998. Both conditions show abnormal accumulation of bis-retinoids that lead to photoreceptor and RPE cell death. The animal models that are currently being used to study AMD therapies are typically Stargardt models. I could continue for an hour about the similarities between the two diseases. Our clinical trial uses outcome measures, namely atrophic lesions that are measured on autofluorescence images that are exactly the same. The dose that we use in both trials is exactly the same.
It's also important to note that pretty much exactly a decade ago, it was shown that fenretinide, which is a less potent RBP4 antagonist, significantly reduced lesion growth in geographic atrophy if RBP4 is reduced by more than 70%. With Tinlarebant, we consistently reach about 80% reduction. I think that Tinlarebant will also show efficacy in GA, and I believe this is a realistic expectation.
Considering the fact that there is a big difference in the patient population between Stargardt disease and GA, what would be the company's go-to-market strategy to help maximize the economics for the company?
Yeah, since the PHOENIX trial, as I mentioned, is about two years behind and we will need a second registration trial in GA, the time difference will be almost five years. We'll put our current efforts to commercialize Stargardt first, which is an orphan indication. The price will be much higher for Stargardt, and to get the therapy to the patients will be much easier since patients are being seen by retinal specialists and typically even by subspecialists. We call them IRD specialists, inherited retinal disease specialists. There are professional networks in the U.S. and worldwide that cover Stargardt, and we are very well connected to those.
Do you think Tinlarebant has the potential to become a first-line therapy for GA patients considering its oral therapy?
Tinlarebant addresses photoreceptor and RPE survival by reducing toxicity at these retinal layers, whereas complement inhibition, as an example, targets an inflammatory response. The two approaches may well be complementary. However, the route of administration is obviously quite different. Monthly intravitreal injections come with significant risk and burden for both patients and healthcare providers. If Tinlarebant as an oral once-a-day tablet shows efficacy that is at least close to what we have seen for the complement inhibitors, then it will very likely become the first-line therapy for GA.
When do patents covering Tinlarebant start to expire?
Yeah, we have 14 active patent families, mostly composition of matter patents, that will last until at least the year 2040 without patent term extension.
Considering the company's deal yesterday, does the company currently have sufficient capital to complete all phase III trials?
Until yesterday, indeed, Belite held about $160 million cash, which equals four years of cash runway with the current program. With the current capital, we can complete all of our ongoing programs, including the PHOENIX trial in GA. As you mentioned yesterday, Belite Bio announced up to $275 million upsized private placement financing by leading healthcare investors. This puts us in a very strong position to commercialize Stargardt now.
Could you give us a summary of the upcoming catalyst within the next 12 months?
Yes, happy to. By Q4 2025, the DRAGON 2 trial will be fully enrolled. By the end of the fourth quarter of 2025, we will have the top-line data readout for the DRAGON trial. NDA submission is anticipated in the first half of 2026. We anticipate to perform an interim analysis of the PHOENIX trial when all patients will have completed the 12-month treatment, which should be in the third quarter of next year.
Regarding the DRAGON 2 trial, when do you expect it to report top-line data?
The DRAGON 2 trial is more than one year behind. We will be fully enrolled by the end of the year. Interim analysis would be, if we perform an interim analysis, a year later. Two years later, we would have the top-line data.
That is not required for U.S. submission.
That's a very good point. We anticipate to receive market authorization based on one trial. We discussed that with various regulatory agencies. The FDA mentioned it will be a review issue, but we anticipate that the DRAGON trial, the current DRAGON trial, will be sufficient for market authorization.
With respect to the Japanese market, you do need data from the DRAGON 2 trial, correct?
This is indeed why we're actually performing the DRAGON 2 trial, because Tinlarebant received the Sakigake designation in Japan, which can be translated as breakthrough designation. The Japanese authority, the PMDA, mandated us to treat Japanese patients, at least 10. These patients were enrolled into the DRAGON 2 trial. We took an opportunistic approach to run another registration trial and wanted to enroll patients that were waiting for Tinlarebant in the U.S. and the U.K. We named that trial DRAGON 2. It's not the case that we would need two registration trials to get the product to the market.
Any questions from the audience?
Nope.
Any closing remarks, Dr. Scholl?
No, thank you for having me.
OK, great. Thank you.