Okay, we can start?
Yes.
Welcome to H.C. Wainwright, our 26th Annual Global Investment Conference. My name is Yi Chen. I'm a healthcare analyst at H.C. Wainwright. For this session, I have the pleasure of chatting with Dr. Nathan Mata, Chief Scientific Officer of Belite Bio. Welcome.
Thank you, Yi. Thanks for the invitation.
Let's start with the recent news. I know Belite recently appointed Dr. Scholl -it's Dr. Scholl? Dr. Scholl as Chief Medical Officer. Could you tell us, what Dr. Scholl brings to the company?
An immense amount of experience. Dr. Scholl is a premier clinician and medical scientist in the fields of both Stargardt disease and geographic atrophy. He led the largest natural history study of Stargardt's conducted to date, an international consortium of several investigators looking at hundreds of patients with Stargardt disease. So, his expertise in Stargardt disease is unparalleled, and in GA, I could say the same thing. So he has a clinical expertise that is unmatched anywhere, so he brings that to the team, as well as his knowledge of clinical trials analysis of data, et cetera, et cetera. So nothing but positive benefits, he's bringing to the Belite management team.
Got it. So, switching to the topic of Stargardt disease, could you tell us the current status of the phase III DRAGON trial of Tinlarebant?
Yeah, yeah. So the phase III study is doing quite well. A majority of patients have passed their twelve-month visit date. So we're looking forward to the interim analysis, which should be coming up at the end of this year. The readout for that is pending, because, again, because Dr. Scholl has. He was actually the chair of our Stargardt's phase III trial, so now that he's stepping down and becoming the CMO, we have to replace that chair, so there could be a little bit of a delay there. But we're targeting end of the year ... probably first quarter of next for that readout on the interim analysis. So we're very excited, given the positive phase II data that we've seen in the open-label study in adolescent Stargardt disease.
Could you tell us a bit more in detail, what do you expect to announce from the interim analysis?
Yeah, so unfortunately, we won't be able to disclose a treatment effect. This is per FDA guidance. By doing so, you would essentially bias the study. So if you tell patients that there's X amount of treatment effect, there could be a psychological bias, not just to them, but also to the principal investigators. So we won't be doing that, but our DSMB will be doing an unmasked analysis of the data, and they will tell us, they will inform us what the different scenarios could be. The real reason for that interim analysis was to do a sample size re-estimation to determine if we needed to add additional subjects to maintain the conditional power. So they will inform us of whether or not we need to do that or not.
So again, we won't be able to disclose the treatment effect, but based upon the information the DSMB gives us, we'll have some sense of where we are in terms of a efficacy effect.
Got it. Could you remind us the dosing schedule in the DRAGON trial, and what, how is the primary efficacy measured in the trial?
Yeah. So the primary endpoint for the Stargardt study and the GA study is to slow lesion growth, and the dosing is oral once a day. This drug, our drug, Tinlarebant, is designed to reduce the accumulation of toxins, which lead to lesion growth in the back of the eye of these patients with Stargardt disease. So we intend to stop the growth of that lesion. That is the accepted endpoint for the FDA, and so we look serially over time at the lesion growth, and we compare the treatment arm to the placebo arm, and we're looking for a difference in that growth rate.
Mm-hmm. And what are the safety and efficacy results observed in prior trials?
So in the phase II study, which is probably the most clear example of both safety and efficacy outcomes from a two-year study, we've seen very, very wonderful safety outcomes. No systemic drug-related AEs whatsoever over two years of dosing. It's 5 milligrams per day. This is an oral tablet that these kids are taking, as well as the GA subjects. And you would expect that there would be some sense of systemic AEs. There's no drug-related systemic AEs whatsoever. The anticipated ocular AEs that we see are, in fact, very important because they're being tolerated very well. They're mild, they're transient, and it's important that we see these adverse events in the ocular tissue because it tells us we're having the intended biological effect on the retina. Without this readout, we would not see that.
So safety is looking really, really good. In terms of efficacy, it was an open-label study, so unfortunately, we don't have a comparator, but we can compare to natural history. And of course, now we have the expertise of Dr. Scholl, who, as I said before, has run the largest natural history study in Stargardt's conducted to date. And he looks at our data and says: Yes, in fact, we're having a treatment effect against slowing lesion growth. So positive safety outcomes, positive efficacy outcomes from that open-label study.
Got it. What's the current estimated timeline for a top-line readout from the DRAGON trial?
Yeah, so for the DRAGON study, we're getting the interim, again, at the end of this year. So one year from that time point, so perhaps early 2026, would be the top-line phase III readout from that two-year study.
Got it, got it. I know you're also conducting a DRAGON II trial, right?
Yes.
Which enrolls a few patients in Japan.
Yes.
You can use those Japanese patients' data, along with the DRAGON trial data, to apply for approval in Japan under the Sakigake Designation, right?
Yes, yes.
Does that mean you, for the DRAGON II trial, you will be able to report Japanese patient data before the top line data of the DRAGON II trial?
You know, that's- it's tough to say. Everything depends on the timing. Probably the only data we would be able to disclose prior to the phase III would be the PK/PD data, because the way this study is being run in Japan, we call DRAGON II, we're first doing a PK/PD study in the Japanese subjects to make sure that the drug is behaving the same way in those patients as we've seen in U.S. patients and patients all around the world. So that's an important thing to establish first. We want to get that information out, but then comes the two-year study. So we probably won't be disclosing any data from the DRAGON II study before the phase III DRAGON study.
Okay, okay. Got it... Is there any approved therapy for Stargardt disease in Japan right now?
There's no approved treatment, and I think this is why the Japanese regulatory authorities have really been after us to get this trial enrolled. In fact, they wanted us to enroll these Japanese subjects in the DRAGON study, but our enrollment was just so far ahead of their regulatory process, we would have delayed our trial. So we decided to go without in the DRAGON, and then use this DRAGON II study to to adopt. But yes, I think that there's an unmet need in Japan, and the fact that the regulatory agencies are pushing us to get this study done, and they've given us a Pioneer Drug Designation, which you mentioned is Sakigake. It's like having clinical Breakthrough Therapy designation here in the U.S. Pretty significant. So I think they're very motivated to get this drug approved.
Got it, got it. How many Stargardt disease patients are seeking treatment in Japan versus patients in the U.S.?
That's really tough to say. In fact, I, you know, what's really important to know is that there's never been a formal epidemiological study of the prevalence of Stargardt disease anywhere. The number that everyone cites, this one in 10,000 or one in eight to 10,000, is really an observational estimate that was made by one investigator, Dr. Podgorski, back in 1988. There never has been a real good study. So in the U.S., we think it's gonna be roughly 30,000 patients, based on that one in 10,000 prevalence. In Japan, we expect a similar prevalence, but because there's a population that's lower, there'll be smaller market size there in Japan. But we think the prevalence is actually gonna be pretty much the same.
Okay, okay. I mean, if approved, do you think Tinlarebant could face competition on the market worldwide?
Yeah, I mean, you know, the fact is there is another competing company that does have an oral therapeutic, that arguably you could say is ahead of ours because they did start their trials way before us. This is a privately held company, so it's very difficult to tell sort of where they are in their drug development. But if you read press releases and you look at clinicaltrials.gov, the only thing you can infer is that perhaps they'll be, they say, filing for an NDA at the end of this year. We're a little skeptical about that. It could be a rolling NDA, perhaps. But yes, the short answer is yes, there will be competition. Whether or not that will be competition towards approval, really remains to be seen. We're moving pretty fast now, and we haven't heard much from Alkeus on their GA study.
But in Stargardt disease, we know they did a phase II- that they received clinical Breakthrough Therapy designation for, but we haven't heard anything about their phase III development thus far. So it remains to be seen, but that is our closest competitor.
Got it. Could you tell us a bit more about the natural progression of Stargardt disease? How fast does it develop, and what patients are hoping for from a treatment?
That's a really good question because a lot of people don't realize that there's actually two populations of Stargardt's disease. There's a population of juveniles and adolescents, and then there's a population of older adults. If you're a child and you get diagnosed with Stargardt's disease, typically it happens between six and eight years old. With that diagnosis, if you have, in fact, severe mutations, it's predicted that you will be legally blind by the age of 20. So it's a very rapidly progressive disease in the juvenile context, and that's why we're focusing on juveniles and adolescents in our trial. Because, again, it's a much greater unmet need. These are children going blind.
We believe that with our drug, we can actually target the disease at an early stage. Get these kids very early before their disease really starts robbing them of vision. It's, in a way, it could be considered a preventative type of measure by going after these early-onset patients who have a much more rapidly progressive disease. The adult patients, they progress as well, but at a much slower rate. There's greater variability in their progression. So it's harder to predict what their growth rate will be over, say, a two-year period. So much less is known about that population.
Got it, got it. So switching to the topic of geographic atrophy ... you are also conducting a phase III PHOENIX trial, right?
Yes, yes.
Of Tinlarebant, so what is the current status of this trial?
Yeah, so that trial is still enrolling. I believe during our last team meeting, we were somewhere around 215 subjects out of 429, that's what we're shooting for. So we're just a little bit behind our pace, but we still plan to close that enrollment in Q1 of 2025. So that's coming up. But we have really some of the greatest centers and institutes involved in that study all across Europe, Asia, America. So this is a very big, global study and we're getting a lot of really good feedback from PIs that want to be in this study because they are clamoring for an oral treatment. Right now, there's a tremendous treatment burden on GA patients because the approved products are intravitreal injections.
Right
... of complement inhibitors and there are safety concerns with those injections. So in addition to the treatment burden, there's a safety concern that physicians worry about. In fact, many of them have stopped prescribing the Apellis drug because of a very significant ocular AE that causes patients to go blind. It's rare, but it is happening. So, the investigators, and many of them have stopped wanting to prescribe it, and they're looking for an oral alternative. So there's a lot of motivation about evaluating safety and efficacy of oral treatments like ours, Tinlarebant.
Okay. So Tinlarebant can treat the patients targeted by existing GA treatment, right?
Yes.
But you can also treat patients that are potentially earlier, at earlier stage of the disease, right?
Yeah.
That the existing treatment cannot touch, right?
That's a really good point because the currently approved treatments are essentially anti-inflammatory agents. So they quell an inflammatory response that's associated with late-stage disease progression. In early-stage disease, where you have smaller lesions, there's little to no inflammation. So those types of therapeutics would not be effective in patients who have early-stage disease. They still have the same pathology, it's just smaller. That's like the lesions are smaller. Our drug will be more effective against those smaller lesions. It will be effective in large, large lesions, too. But once you get those larger lesions, now you have a more complex disease process where inflammation is triggering all sorts of other things that perhaps may be as responsive to our treatment as if you had started earlier, before that inflammatory insult began.
So, so we should expect the PHOENIX trial to read out after the DRAGON I and II trial?
Yeah, yeah. And there's a cadence here because all the trials are two years in duration. So let's say, for instance, if in fact we are able to close enrollment of the PHOENIX trial in Q1 of 2025, then Q1 of 2026 would be the interim analysis, and then Q1 of 2027 would be the top-line phase III data from the GA PHOENIX study.
Mm-hmm. Got it. Could you talk about the patent portfolio, and when does the patent for Tinlarebant expire?
You see, we have an incredibly strong patent portfolio, 14 active patent families. The majority of these are composition of matter patents. Without any patent term extension, let's say our first expiring patent would be, like, 2040. With patent term extension, we could go out to 2045. We have a really strong, robust patent portfolio, which includes all over the world.
Got it.
It's global. Great protection, and again, composition of matter is the majority of those patents, profiles.
Okay, got it. Now, could you give-- just give us a brief review of the upcoming catalysts within the next 12, 18 months?
Right, yeah. So, of course, I mentioned the interim analysis from the Stargardt disease, so that'll be, hopefully, you know, early, either late this year or early 2025. That's the first one. Then, of course, right after that, we have, one year later, would be the phase III data, as I mentioned. But sort of in the middle, obviously, we want to be able to announce the closure of enrollment of the GA study. So that will sort of coincide with the interim analysis in roughly early 2025, so those will happen too. And of course, then we'll follow the closure of that phase II/III study, the DRAGON II study in Japan, which also, by the way, is including patients in U.K. and U.S. So we'll have a close of enrollment somewhere in the middle, hopefully, of 2025, maybe or later part of 2025.
So there's a few catalysts going on, a couple of data readouts, some closing of enrollments in these studies we have. So we're very excited to see what happens over the next six months to one year.
Got it. Great. And so the company is well-funded to carry on the operations for, I guess, two years?
Easily. Easily. Yeah, maybe even a three-year runway. We certainly have enough money to complete the current studies we have going on. So no, no problem with that.
Okay. And by the way, if Tinlarebant is approved for juvenile Stargardt disease, it is qualified for a priority review voucher?
Yeah, absolutely, because we do have orphan disease status not just here, but also in the U.K. and Japan now with the Sakigake Designation. Yes, so the short answer is yes, we would get that preferred priority review voucher which of course, has a monetary value. It could be in the neighborhood of $100 million with approval. So that's another potential milestone, if you will. But again, just having that phase III data read out positively would be significant enough for us.
Got it. Got it. Great. I guess my last question is, what do you think is the key takeaway, takeaway message for investors today, and, you know, why investors should pay attention to Belite Bio?
Yeah, I think, you know, the differentiators, right? As I keep mentioning, oral once-a-day treatment, okay, early intervention. These are two things I think investors should be really keenly aware of because other companies don't have those advantages. I mentioned there is another company going after an oral therapeutic. They were going after later-stage Stargardt's. I don't know what they, how they've changed, but we are really the originators of the early intervention with these smaller, smaller lesions.
And the fact is that in the phase II open-label study, I think investors should look at that data very closely. Even though there's no comparator arm, we have natural history to compare to, which is very, very reliable. There's not a lot of variability, as I said before, in this early-stage disease. So when you look at the safety outcomes of that phase II study, you look at the efficacy outcomes of that study in terms of slowing lesion growth, and not only that, we slowed the transition of an early lesion type to a late lesion type. So it tells us the MOA is working perfectly. So when you look at all that and you look at the positive outcomes from that phase II study, nothing has changed in the phase III trial design.
Patient population is the same, endpoint is the same, drug is the same, duration is the same. So we expect that that phase II data is a very good indicator of what we'll be able to see in the phase III. So I think investors should pay attention to that. Because even though that was an open-label study, there's value there that I think they can use to de-risk, in their head at least what could happen potentially in our phase III DRAGON study.
Got it. Got it. Okay, great. That's a very informative chat. Thank you very much, Nathan.
Thank you again for participating.
Best wishes for your clinical trial.
Appreciate it. Thank you very much, and thank you all.